Healthy Diet and Physical Activity for Cardiovascular Disease Prevention in Adults With Cardiovascular Risk Factors: Behavioral Counseling Interventions
November 24, 2020
Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
By Elizabeth A. O’Connor, PhD; Corinne V. Evans, MPP; Megan C. Rushkin, MPH; Nadia Redmond, MSPH; Jennifer S. Lin, MD, MCR.
The information in this article is intended to help clinicians, employers, policymakers, and others make informed decisions about the provision of health care services. This article is intended as a reference and not as a substitute for clinical judgment.
This article may be used, in whole or in part, as the basis for the development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.
This article was published online in JAMA on November 24, 2020 (JAMA. 2020;324(20):2076-2094. doi:10.1001/jama.2020.17108).
Importance: Cardiovascular disease is the leading cause of death in the US, and poor diet and lack of physical activity are major factors contributing to cardiovascular morbidity and mortality.
Objective: To review the benefits and harms of behavioral counseling interventions to improve diet and physical activity in adults with cardiovascular risk factors.
Data Sources: MEDLINE, PubMed, PsycINFO, and the Cochrane Central Register of Controlled Trials through September 2019; literature surveillance through July 24, 2020.
Study Selection: English-language randomized clinical trials (RCTs) of behavioral counseling interventions to help people with elevated blood pressure or lipid levels improve their diet and increase physical activity.
Data Extraction and Synthesis: Data were extracted from studies by one reviewer and checked by a second. Random-effects meta-analysis and qualitative synthesis were used.
Main Outcomes and Measures: Cardiovascular events, mortality, subjective well-being, cardiovascular risk factors, diet and physical activity measures (eg, minutes of physical activity, meeting physical activity recommendations), and harms. Interventions were categorized according to estimated contact time as low (<30 minutes), medium (31-360 minutes), and high (>360 minutes).
Results: Ninety-four RCTs were included (N = 52,174). Behavioral counseling interventions involved a median of 6 contact hours and 12 sessions over the course of 12 months and varied in format and dietary recommendations; only 5% addressed physical activity alone. Interventions were associated with a lower risk of cardiovascular events (pooled relative risk, 0.80 [95% CI, 0.73-0.87]; 9 RCTs [n = 12,551]; I2 = 0%). Event rates were variable; in the largest trial (Prevención con Dieta Mediterránea [PREDIMED]), 3.6% in the intervention groups experienced a cardiovascular event, compared with 4.4% in the control group. Behavioral counseling interventions were associated with small, statistically significant reductions in continuous measures of blood pressure, low-density lipoprotein cholesterol levels, fasting glucose levels, and adiposity at 12 to 24 months’ follow-up. Measurement of diet and physical activity was heterogeneous, and evidence suggested small improvements in diet consistent with the intervention recommendation targets but mixed findings and a more limited evidence base for physical activity. Adverse events were rare, with generally no group differences in serious adverse events, any adverse events, hospitalizations, musculoskeletal injuries, or withdrawals due to adverse events.
Conclusions and Relevance: Medium- and high-contact multisession behavioral counseling interventions to improve diet and increase physical activity for people with elevated blood pressure and lipid levels were effective in reducing cardiovascular events, blood pressure, low-density lipoproteins, and adiposity-related outcomes, with little to no risk of serious harm.
Risk factors for cardiovascular disease (CVD), such as high blood pressure and high cholesterol and lipid levels, are common in the US and contribute to excess mortality.1 Counseling to encourage a healthy diet and physical activity in populations with CVD risk factors can improve blood pressure, cholesterol levels, and other outcomes.2 While observational evidence shows associations between lower levels of CVD risk factors and lower cardiovascular-related mortality,3-5 trial evidence regarding the effectiveness of behavioral counseling on reducing CVD events and mortality is sparse.
This systematic review was conducted to provide updated evidence on the benefits and harms of behavioral counseling for healthy diet and physical activity in adults with CVD risk factors to inform an update of the 2014 US Preventive Services Task Force (USPSTF) recommendation.6 In 2014, the task force recommended offering or referring adults who were overweight or had obesity and had additional CVD risk factors to intensive behavioral counseling interventions to promote a healthy diet and physical activity for CVD prevention (B recommendation). This review was conducted in parallel with a review addressing abnormal blood glucose levels7 and complements other USPSTF reviews related to primary prevention of CVD.8-13
Scope of Review
This review addressed 4 key questions (KQs) (Figure 1). Methodological details including study selection, a list of excluded studies, additional data analysis methods, detailed study-level results for all outcomes, and contextual observational data are available in the full evidence report.15
Data Sources and Searches
MEDLINE, PubMed (publisher-supplied records only), PsycINFO,and the Cochrane Central Register of Controlled Trials were searched to identify literature published after the previous review for the USPSTF.16 Searches covered literature published January 2013 through September 2019. All studies in the prior review16 were also evaluated, as well as reference lists of related systematic reviews.9,17
ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform were searched for relevant ongoing trials. Active surveillance was conducted through July 24, 2020, via article alerts and targeted journal searches to identify major studies that might affect the conclusions or understanding of the evidence. None were identified.
Investigators reviewed 14,409 unique citations and 466 full-text articles against a priori inclusion criteria (Figure 2). Disagreements were resolved via discussion and consultation with another reviewer. Eligible studies were fair- and good-quality RCTs that evaluated the effectiveness of primary care–relevant interventions of behavioral counseling for diet and nutrition, physical activity (including sedentary behavior), or both in adults with CVD risk factors. Studies had to target populations at increased risk of CVD due to hypertension or elevated blood pressure, dyslipidemia, or through examination of multiple risk factors. These could include estimated 10-year CVD risk of 7.5% or higher (eg, using the Pooled Cohort Equations18 or Framingham risk calculators19), presence of metabolic syndrome, or having any of multiple CVD risk factors as long as hypertension/elevated blood pressure and dyslipidemia were among them. In contrast to the review to support the 2014 recommendation, the current review excluded studies limited to or predominantly in populations with diabetes or prediabetes because a separate systematic review will address these populations.7 In addition, weight loss trials targeting people with relevant CVD risk factors were included in this review but not in the previous review.
Interventions could be delivered alone or as part of a larger intervention that also addressed other health behaviors (eg, smoking cessation). Additionally, interventions had to have been conducted in countries with “very high” human development according to the United Nations20 and take place or be feasible in a health care setting. Studies had to report a health outcome (eg, CVD events, mortality), intermediate outcome (eg, blood pressure, lipid levels, glucose levels, adiposity), or behavioral outcome (eg, dietary intake, physical activity) or report adverse events related to the intervention. Comparative effectiveness trials without a true control group were excluded.
Data Extraction and Quality Assessment
Two reviewers independently assessed the methodological quality of eligible studies using criteria outlined by the USPSTF.14 Each study was assigned a quality rating of “good,” “fair,” or “poor,” and disagreements between investigators were resolved through consensus after discussion with additional investigators. Studies rated as poor were excluded.14 Poor-quality studies typically had several major risks of bias, including very high attrition (generally >40%), differential attrition between intervention groups (generally >20%), substantial lack of baseline comparability between groups without adjustment for those variables, or other issues judged to considerably bias the results (eg, possible selective reporting, inappropriate exclusion of participants from analyses, questionable validity of randomization and allocation concealment procedures). One reviewer abstracted descriptive and outcome data from each included study into standardized evidence tables; a second checked for accuracy and completeness.
Data Synthesis and Analysis
Summary tables were created for study characteristics, population characteristics, intervention characteristics, and outcomes. Methods consistent with the previous review were used to estimate and categorize the total contact time of each intervention group as low (≤30 minutes), medium (31-360 minutes [6 hours]), or high (>360 minutes).
All outcomes were quantitatively pooled except for patient-reported measures of subjective well-being (KQ1), dietary pattern scores (KQ3), and adverse events (KQ4), which were summarized descriptively. For mortality and cardiovascular event outcomes (KQ1), results for multiple intervention groups were combined because the absolute number of events was generally small.
Meta-analyses for intermediate (KQ2) and behavioral (KQ3) outcomes were conducted using the most comprehensive or highest-contact intervention group if a study had multiple intervention groups and using the follow-up time point closest to 12 months if there were multiple follow-up assessments. Adjusted effect estimates reported by primary studies were used over unadjusted values, and crude effect estimates were calculated if between-group results were not reported. For pooling, the Restricted Maximum Likelihood model with the Knapp-Hartung correction21,22 was used. The presence of statistical heterogeneity among the studies was assessed using standard χ2 tests, and the magnitude of heterogeneity was estimated using the I2 statistic. Meta-regression and stratified analyses were conducted to explore whether there were methodologic, population, or intervention characteristics at the study level that were associated with effect size for the most commonly reported outcomes of systolic blood pressure (SBP), total cholesterol, and weight. In addition, small-study effects were evaluated using funnel plots and the Egger test.23
Stata version 15.1 (StataCorp) and R version 3.5.2 (R Foundation for Statistical Computing) were used for all quantitative analyses. All significance testing was 2-sided, and results were considered statistically significant at P < .05.
The aggregate strength of evidence was assessed for each KQ using the approach described in the Methods Guide for Effectiveness and Comparative Effectiveness Reviews,24 based on the number, quality, and size of studies and the consistency and precision of results between studies.
Ninety-four randomized and cluster-randomized clinical trials reported in 227 publications were included (N = 52,174) (Figure 2).25-250 Fifty-two trials were carried forward from the previous review30,31,35,37,40-42,45,53,55,56,61-63,72,74,80, 87,90,99,121,123,130,131,134,138,145,147,149,155,174,176-178,180,181,192,193,208,210,215, 217,223,225,227,229,231,234,238,242,244,247 and were synthesized with 42 newly identified trials.36,46-48,51,69-71, 73,92,97,110,111,115,118,124,127,132,139,142,144,148,152,158,163,165,182,183,187,190,194,196,200,203,205,207,216,220,221,237, 241,245 Of 94 studies, 32 (34.0%) were limited to people with hypertension or elevated blood pressure, 16 (17.0%) were limited to those with dyslipidemia or elevated lipid levels, and the remaining 46 (49.0%) included people with any of multiple risk factors (Table 1). Most participants were overweight or had obesity, and the mean baseline body mass index (BMI) was 29.8 (calculated as weight in kilograms divided by height in meters squared). Forty-three trials (45.7%) were conducted in the US; of these, 16 trials appeared to include majority Hispanic or non-White samples. The majority of trials recruited participants from health care settings, but most interventions did not involve a primary care clinician. Almost all trials addressed diet, with or without physical activity, and had at least 30 minutes of contact time. Very few intervention groups (6/120 [5.0%]) addressed physical activity alone. The median number of contacts was 12 (interquartile range [IQR], 5-27), with an estimated 6 (IQR, 2.2-15.8) hours of contact over 12 (IQR, 6-18) months. Interventions varied widely in format and dietary recommendations, and 23 (19.2%) also included medication management.
Benefits of Interventions
Key Question 1. Do primary care–relevant behavioral counseling interventions to improve diet, increase physical activity, and reduce sedentary behavior improve CVD and related health outcomes (eg, morbidity, mortality) in adults with known CVD risk factors (hypertension or elevated blood pressure, dyslipidemia, or mixed or multiple risk factors [eg, 10-year CVD risk >7.5%, metabolic syndrome])?
Twenty-nine of the 94 studies reported health outcomes. Of these, 12 trials reported CVD events, with follow-up ranging from 6 months to 16 years.37,46,47,55,97,99,124,127,220,221,241,242 All had medium or high intervention contact time. Behavioral counseling was associated with lower risk of the composite outcomes of any CVD events (risk ratio [RR], 0.80 [95% CI, 0.73 to 0.87]; 9 RCTs [n = 12,551]; I2 = 0%), myocardial infarction (RR,0.85 [95% CI,0.70 to 1.02]; 6 RCTs [n = 10,375]; I2 = 0%), and stroke (RR, 0.52 [95% CI, 0.25 to 1.10]; 4 RCTs [n = 9800]; I2 = 0%), although the pooled effect size showed a statistically significant association only for the composite outcome of any CVD events (Figure 3). Only 3 of these trials were included in the previous review.37,99,242 The newly included Prevención con Dieta Mediterránea (PREDIMED) study97 was heavily weighted in this analysis because of its large sample size; however, the association remained statistically significant in a sensitivity analysis excluding PREDIMED (RR,0.79 [95% CI,0.70 to 0.90]; 8 RCTs [n = 5104]). Event rates were variable; in PREDIMED 3.6% in the intervention groups experienced a cardiovascular event, compared with 4.4% in the control group. Few studies were powered for mortality, and neither individual large studies nor the pooled estimate showed a beneficial association with all-cause mortality (RR, 0.89 [95% CI, 0.71 to 1.11]; 18 RCTs [n = 17,939]; I2 = 0%) with follow-up of 6 months to 16 years. Among 3 large trials,97,99,221 findings for both all-cause and cardiovascular mortality indicated greater benefit for intervention participants relative to control participants; however, results were statistically significant in only 1 trial.99 Patient-reported well-being measures were reported in 11 trials,36,37,42,62,99,110,115,124,148,200,231 but group differences were generally very small and statistically nonsignificant.
Key Question 2. Do primary care–relevant behavioral counseling interventions to improve diet, increase physical activity, and reduce sedentary behavior improve intermediate outcomes associated with CVD (eg, blood pressure, lipid levels, blood glucose levels, body mass index) in adults with known CVD risk factors (hypertension or elevated blood pressure, dyslipidemia, or mixed or multiple risk factors [eg, 10-year CVD risk >7.5%, metabolic syndrome])?
All but 3 trials reported intermediate outcomes.87,180,231 Behavioral counseling interventions were associated with small, statistically significant reductions in continuous measures of blood pressure, low-density lipoprotein cholesterol (LDL-C) and total cholesterol levels, fasting glucose levels, and adiposity-related outcomes at 12 to 24 months’ follow-up (Table 2).
There was a mean 1.8-mm Hg/1.2-mm Hg greater reduction in blood pressure in intervention groups vs control groups after 12 to 24 months (pooled SBP mean difference, –1.8 [95% CI, –2.5 to –1.1]; 42 RCTs [44 effects, n = 14,580]; I2 = 37.3%; pooled diastolic blood pressure mean difference, –1.2 [95% CI, –1.6 to –0.8]; 38 RCTs [40 effects, n = 13,098]; I2 = 32.5%). In addition, in trials reporting incidence of hypertension, intervention groups had a 26% lower risk of onset (pooled RR, 0.74 [95% CI, 0.58 to 0.94]; 5 RCTs [n = 2707]; I2 = 12%).
For lipid levels, the pooled mean difference in change between groups was –3.5 mg/dL for total cholesterol, –2.1 mg/dL for LDL-C, and 0.6mg/dL for high-density lipoprotein cholesterol (pooled total cholesterol mean difference, –3.5 [95% CI, –5.6 to –1.4]; 36RCTs [38 effects, n = 11,414]; I2 = 65.9%; pooled LDL-C mean difference, –2.1 [95% CI, –4.1 to –0.2]; 30 RCTs [32 effects, n = 8894]; I2 = 55.9%; pooled high-density lipoprotein cholesterol mean difference, 0.6 [95% CI, 0.2 to 1.0]; 32 RCTs [34 effects, n = 8974]; I2 = 33.7%). Among 20 trials reporting fasting glucose levels, there was a mean 2.3-mg/dL greater reduction in fasting blood glucose in the intervention groups compared with the control groups at 12 to 24 months’ follow-up (mean difference, –2.3 [95% CI, –3.6 to –1.0]; 20 RCTs [22 effects, n = 5950]; I2 = 82.5%).
At 12 to 24 months, the intervention groups showed slightly greater reductions in all 3 adiposity-related measures: pooled BMI mean difference, –0.5 (95% CI, –0.7 to –0.3); 30 RCTs (n = 9909); I2 = 83.3%; pooled weight mean difference, –1.6 kg (95% CI, –2.1 to –1.1); 37 RCTs (n = 16 345); I2 = 88.1%; pooled waist circumference mean difference, –1.7 cm (95% CI, –2.4 to –1.1); 23 RCTs (n = 11,708); I2 = 87.3%). Incidence of diabetes and metabolic syndrome were sparsely reported; findings usually favored the intervention group, although they were generally not statistically significant.
Very few intervention or population characteristics were clearly associated with effect size consistently across outcomes. Meta-regression and stratified analyses were conducted for the most commonly reported outcomes: SBP, total cholesterol level, and weight. Total cholesterol was chosen over LDL-C because it was more commonly reported; however, absolute effect sizes were typically very similar between these 2 outcomes, suggesting that most of the change in total cholesterol was due to changes in LDL-C. In these analyses, there was no clear indication for any outcome that high-contact (>360-minute) trials showed larger effects than medium-contact (31- to 360-minute) trials, nor was there an association between continuous measures of contact (number of sessions, total estimated minutes of contact) and effect size. However, very few trials offered low-contact (<30- minute) interventions. The analyses of SBP demonstrated generally consistent effects among studies with various characteristics, including study quality, setting, baseline weight selection and weight loss approach, some key intervention characteristics, and socioeconomic status (eFigure 1 in the Supplement).
For total cholesterol, a number of study characteristics showed statistically significant bivariate associations; however, multivariable models suggested only larger reductions in trials with medication management components (P = .003) and those focusing on older adults (P = .03).
While several characteristics showed statistically significant bivariate associations with the effect size for weight, the correlated nature of these characteristics made it difficult to disentangle the results; a multivariable model suggested larger effects were found in weight loss trials (P < .03). The test of small-study effects was statistically significant for only the outcome of weight (Egger test of bias, –2.8; P < .001), indicating that smaller trials tended to have larger effects. Weight loss trials tended to be smaller (mean sample size, 461, compared with 585 in non–weight loss trials). Four trials had multiple intervention groups that allowed for the direct comparison of weight loss vs other messages to improve intermediate outcomes.132,158,220,221 All 4 were trials among people with hypertension that had both weight loss and sodium reduction (without weight loss) interventions; blood pressure consistently improved even without encouragement to lose weight. Based on direct within-study comparisons using study-reported subgroup analyses, there was no indication that any demographic subpopulations consistently benefited more or less than others.37,47,62,63,69,70,74,97,99,121,130,134,147,155, 158,181,183,193,194,200,216,217,220,221
No single optimal or representative intervention was identified, and a wide range of behavioral counseling approaches improved health profiles. Among programs that showed a clear benefit, group-based programs generally offered 5 to 12 sessions over 4 to 12 months or, if weight loss was a primary focus, 20 to 30 sessions over 24 months.
One-on-one interventions were generally shorter than group-based interventions, and individually delivered interventions usually fell into the medium contact category, while high contact trials usually involved groups, often in addition to individual contact.
Among interventions showing a benefit, motivational interviewing was often used, and common behavior-change techniques included goal setting, active self-monitoring, and addressing barriers related to diet, physical activity, or weight change.
Key Question 3. Do primary care–relevant behavioral counseling interventions to improve diet, increase physical activity, and reduce sedentary behavior improve behavioral outcomes (eg, diet, physical activity, sedentary behavior) in adults with known CVD risk factors (hypertension or elevated blood pressure, dyslipidemia, or mixed or multiple risk factors [eg, 10-year CVD risk >7.5%, metabolic syndrome])?
Seventy of the 94 included trials reported some type of behavioral outcome (n = 43,243).30,31,35,37,40,41,45-48,51,53,55,61,63,70-72,74, 80,87,90,92,97,110,115,121,123,124,127,130-132,142,145,148,149,152,155,158,163,165,174,177,180,182,190,193,196,200,205,207,208,210,215-217,220,221,223,225,229,231,234,237, 238,241,244,245,247 Specific behavioral outcomes were typically reported by fewer than 15 trials per outcome, and there was substantial variability in measurement for most. Overall, behavioral counseling interventions were associated with dietary improvements, including reductions in saturated fat consumption and increases in the consumption of fruits, vegetables, and fiber (Table 3). The mean difference in reduction in the percentage of calories from saturated fat was 1.5% after 12 to 24 months (pooled mean difference, –1.5% [95% CI, –1.9% to –1.1%]; 15 RCTs [17 effects, n = 6229]; I2 = 72%). For fruits and vegetables, the intervention groups increased consumption by a mean of 0.7 servings per day more than the control groups (pooled mean difference, 0.7 [95% CI, 0.1 to 1.3]; 11 RCTs [n = 4310]; I2 = 90%). The mean increase in fiber consumption was 1.3 g per day (95% CI, 0.1 to 2.6; 5 RCTs [n = 1350]; I2 = 42%) more than control groups. In addition, trials among people with hypertension or elevated blood pressure who were counseled to reduce sodium consumption did show reduced urinary sodium levels (pooled mean difference, –18.0 mmol/L [95% CI, –34.8 to –1.2]; 9 RCTs [n = 3583]; I2 = 89%). Dietary pattern scores generally showed statistically significantly greater improvement in intervention groups, but measurement was heterogeneous and interpretation of effect sizes was unclear.
Physical activity outcomes were highly variable in terms of both measurement and results, with minimal evidence to suggest that interventions were associated with increased physical activity. In the 50 trials reporting some type of physical activity outcome, the reported measures and the units of measure were disparate, and almost all outcomes were self-reported. Pooled analyses of continuous physical activity outcomes did not show statistically significant association, with high statistical heterogeneity (pooled standardized mean difference, 0.06 [95% CI, —0.03 to 0.14]; 30 RCTs [32 effects,n = 19,834]; I2 = 64%), and a pooled estimate of physical activity minutes per week showed an increase of 9.1 minutes in intervention groups compared with control groups that was not statistically significant (pooled minutes per week mean difference, 9.1 [95% CI, –4.6 to 22.8]; 10 RCTs [11 effects, n = 9746]; I2 = 48%). Dichotomous outcome reporting in terms of meeting study-defined physical activity goals occurred in a small subset of 11 trials, and the pooled effect size suggested a statistically significant benefit associated with intervention groups (pooled RR, 1.22 [95% CI, 1.00 to 1.50]; 11 RCTs [n = 5887]; I2 = 91%).
Harms of Interventions
Key Question 4. What are the harms of primary care–relevant behavioral counseling interventions to improve diet, increase physical activity,and reduce sedentary behavior in adults with known CVD risk factors (hypertension or elevated blood pressure, dyslipidemia, or mixed or multiple risk factors [eg, 10-year CVD risk >7.5%, metabolic syndrome])?
Twenty of the 94 included trials reported harms (n = 18,263).36,37,46,47,55,63,87,97,118,152,187,193,194,200,241,242,247 Seven of these 20 trials reported that there were no adverse events or no serious adverse events,55,87,97,118,148,152,247 and other trials reported 1 or more of the following: serious adverse events, any adverse events, hospitalizations, musculoskeletal injuries, withdrawals due to adverse events, gallbladder disease, and headaches. Adverse events related to diet and physical activity counseling were exceedingly rare, with generally no statistically significant differences in any study for harms outcomes. There was no consistent evidence of paradoxical effects for intermediate or behavioral outcomes.
Consistent with the prior review that was conducted to support the 2014 USPSTF recommendation,16 this review found that medium and high-contact behavioral counseling interventions in people with cardiovascular risk factors were associated with improvements in intermediate and behavioral outcomes. The evidence is summarized in Table 4. No single optimal or representative intervention was identified; a wide range of behavioral counseling approaches improved health profiles. Similar effect sizes were found for most outcomes, compared with the previous review. This was observed despite the inclusion of weight loss studies in adults with relevant CVD risk factors and the exclusion of studies conducted predominantly in adults with prediabetes or diabetes (the latter are addressed in a separate USPSTF review).7
The finding that behavioral counseling interventions were associated with a lower likelihood of CVD events is new since the previous review. The overall pooled effect size showed a 20% lower risk of CVD events, which translates to a number needed to treat of 100 (95% CI, 74 to 154) to prevent 1 CVD event, assuming a baseline rate of 5%. Population risks of 7.5% and 10% translate to numbers needed to treat of 67 (95% CI, 49 to 103) and 50 (95% CI, 37 to 77), respectively.
The largest study was PREDIMED, which accounted for more than one-half of the participants in the analysis and was not included in the previous review.97 PREDIMED investigators issued a retraction of the original publication after the discovery of protocol violations regarding enrollment of household members without randomization and inconsistent use of randomization tables. The published updated analyses, including extensive sensitivity analyses to explore the effect of the violations, found that effect sizes were only minimally affected. Results reported here are from the updated version of the results. The association was still statistically significant in a sensitivity analysis excluding this study. The finding of no consistent evidence of benefit for physical activity outcomes is surprising and may reflect limitations in the evidence. The difference in results between continuous outcomes showing no benefit and dichotomous outcomes showing marked improvement suggests that physical activity reporting is not representative in this body of literature, which included few trials exclusively addressing physical activity. The results of this review stand in contrast to those of another commissioned by the USPSTF that addressed behavioral counseling for diet and physical activity in adults without CVD risk factors.
That review found that behavioral counseling was associated with approximately 35 more minutes per week of physical activity.8 That review also included substantially more trials only addressing physical activity. Indeed, studies whose primary inclusion criterion was suboptimal physical activity were included in that review and not in the present review. The clinical significance of modest improvements in intermediate and behavioral outcomes is challenging to quantify, given that behavioral changes may not be maintained. This may be particularly true for dietary outcomes for which the effect of individual diet components is difficult to evaluate and there is sparse reporting on overall dietary patterns. Regardless, there is observational evidence linking lower levels of CVD risk factors as well as improved diet and physical activity behaviors to better cardiovascular and mortality outcomes. Such evidence is reinforced by trial data suggesting that behavioral counseling for healthy diet and physical activity in adults with CVD risk factors is associated with lower risk of CVD events and by data that suggest little to no harm.
Further understanding is needed regarding the contribution of weight loss in the context of complex behavioral interventions targeting CVD risk factors. Robust analyses of the importance of weight loss on intermediate outcomes are best provided by individual patient–level data and direct within-study comparisons of interventions with and without weight loss goals, both of which are sparse. While many interventions in this review had weight loss goals for all or some participants, some within-study comparisons suggested that CVD risk reduction can occur in the absence of weight loss,132,158,220,221 consistent with a recent comparative effectiveness trial not included in this review because it did not include a true control group.251 While evidence from clinical trials remains limited, observational evidence also supports the benefits of a healthy diet and physical activity for people with excess weight, even in the absence of weight loss. The Nurses’ Health Study and the Health Professionals Follow-up Study252 found that all-cause mortality was lower in people with BMIs of 30.0 to 39.9 who had engaged in at least 3 healthy behaviors (including healthy diet, physical activity, moderate alcohol consumption, and not smoking) than in people of healthy weight who reported only 1 of these behaviors. Thus, for people with excess weight, particularly those with a history of unsuccessful or unhealthy weight loss approaches, promoting diet and physical activity goals without targeting weight loss is likely to improve health.
There are important limitations in the research that should be considered. First, only a small proportion of trials had sufficient sample size and follow-up time to evaluate CVD events and mortality. Continued follow-up and large replication studies are needed. Second, there was highly variable reporting of behavioral outcomes, particularly for physical activity. The variability in specific measures, as well as the lack of behavioral outcomes in studies reporting intermediate outcomes, make it difficult to interpret pooled effect sizes. Third, for dietary outcomes it is difficult to understand the clinical importance of changes in a single aspect of diet. Given the importance of substitutions when modifying diet,253 validated measures of overall diet pattern would be a more valuable outcome; however, the field lacks a consistent measure of overall optimal diet pattern. The Healthy Eating Index is a validated measure of overall diet quality that assesses alignment with the Dietary Guidelines for Americans and is associated with all-cause, CVD, and cancer mortality.254 However, only 2 included studies reported this measure,215,216 and the field would benefit from a set of core outcome measures of diet and physical activity. Fourth, data were very limited for persons 75 years and older. The PREDIMED study had an mean age of 67 years, however, supporting the benefits of dietary counseling adults 65 years and older.
This review has several limitations. First, the review included studies conducted over approximately 30 years, a range of time over which the clinical context has changed. Changes in eating patterns, treatment guidelines, and understanding of nutrition science increase the clinical heterogeneity of participants and the interventions used in these trials. Treatment guidelines for hypertension and dyslipidemia have changed, generally recommending treatment at lower lipid and blood pressure levels. Rates of smoking have declined. Dietary messages and technology platforms have changed, yet evidence for technology-driven interventions without support from a health care professional is scarce. Moreover, the sparse reporting of baseline estimated 10-year CVD risk—coupled with the rarity of trials powered for CVD events—makes it difficult to characterize the risk levels of participants in terms consistent with treatment guidelines informed by 10-year risk.
Second, the wide-ranging study populations and sparsity of within-study subgroup analyses precluded robust analysis of differential effectiveness across patient characteristics. Meta-analytic techniques were used to address effect modification when possible, but such analyses were limited because of the risk of ecological bias; the best analysis of effect modification across patient subpopulations uses individual-level data. Similarly, controlling for the confounding effects of medication use is best addressed in individual level analyses. Individual studies rarely controlled for this potentially important confounding variable.
Third, statistical heterogeneity was high in many of the included meta-analyses. This likely reflected the underlying clinical and methodological heterogeneity in the included studies.
Medium-and high-contact multisession behavioral counseling interventions to improve diet and increase physical activity for people with elevated blood pressure and lipid levels were effective in reducing cardiovascular events, blood pressure, low-density lipoproteins, and adiposity-related outcomes, with little to no risk of serious harm.
Source: This article was first published online in the Journal of the American Medical Association on (JAMA. 2020;324(20):2076-2094. doi:10.1001/jama.2020.17108).
Conflict of Interest Disclosures: None reported.
Funding/Support: This research was funded under contract HHSA-290-2012-00015-I-EPC4, Task Order 6, from the Agency for Healthcare Research and Quality (AHRQ), US Department of Health and Human Services, under a contract to support the US Preventive Services Task Force (USPSTF).
Role of the Funder/Sponsor: Investigators worked with USPSTF members and AHRQ staff to develop the scope, analytic framework, and key questions for this review. AHRQ had no role in study selection, quality assessment, or synthesis. AHRQ staff provided project oversight; reviewed the report to ensure that the analysis met methodological standards, and distributed the draft for peer review. Otherwise, AHRQ had no role in the conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript findings. The opinions expressed in this document are those of the authors and do not reflect the official position of AHRQ or the US Department of Health and Human Services.
Additional Information: A draft version of this evidence report underwent external peer review from 3 content experts (Alice H. Lichtenstein, DSc, PhD [Tufts University]; Penny M. Kris-Etherton, PhD [Penn State University]; and Crystal C. Tyson, MD [Duke University]) and 5 federal partners (National Center for Chronic Disease Prevention and Health Promotion; National Institute on Minority Health and Health Disparities; National Heart, Lung, and Blood Institute; National Institute of Nursing Research; and National Institute of Child Health and Human Development). Comments were presented to the USPSTF during its deliberation of the evidence and were considered in preparing the final evidence review.
1. Patel SA, Winkel M, Ali MK, Narayan KM, Mehta NK. Cardiovascular mortality associated with 5 leading risk factors: national and state preventable fractions estimated from survey data. Ann Intern Med. 2015;163(4):245-253. doi:10.7326/M14-1753
2. Lin JS, O’Connor E, Evans CV, Senger CA, Rowland MG, Groom HC. Behavioral counseling to promote a healthy lifestyle in persons with cardiovascular risk factors: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2014;161(8):568-578. doi:10.7326/M14-0130
3. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R; Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360(9349):1903-1913. doi:10.1016/S0140-6736(02)11911-8
4. Lewington S, Whitlock G, Clarke R, et al; Prospective Studies Collaboration. Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths. Lancet. 2007;370(9602):1829-1839. doi: 10.1016/S0140-6736(07)61778-4
5. Whitlock G, Lewington S, Sherliker P, et al; Prospective Studies Collaboration. Body-mass index and cause-specific mortality in 900,000 adults: collaborative analyses of 57 prospective studies. Lancet. 2009;373(9669):1083-1096. doi:10.1016/S0140-6736(09)60318-4
6. LeFevre ML; US Preventive Services Task Force. Behavioral counseling to promote a healthful diet and physical activity for cardiovascular disease prevention in adults with cardiovascular risk factors: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2014; 161(8):587-593. doi:10.7326/M14-1796
7. Final research plan: abnormal blood glucose and type 2 diabetes mellitus: screening. US Preventive Services Task Force. Published November 2018. Accessed April 11, 2019. https://www.uspreventiveservicestaskforce.org/uspstf/document/final-research-plan/abnormal-blood-glucose-and-type-2-diabetes-mellitus-screening
8. Patnode CD, Evans CV, Senger CA, Redmond N, Lin JS. Behavioral counseling to promote a healthful diet and physical activity for cardiovascular disease prevention in adults without known cardiovascular disease risk factors: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2017;318(2):175-193. doi:10.1001/jama.2017.3303
9. LeBlanc ES, Patnode CD, Webber EM, Redmond N, Rushkin M, O’Connor EA. Behavioral and pharmacotherapy weight loss interventions to prevent obesity-related morbidity and mortality in adults: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2018;320(11):1172-1191. doi:10.1001/jama.2018.7777
10. Piper MA, Evans CV, Burda BU, Margolis KL, O’Connor E, Whitlock EP. Diagnostic and predictive accuracy of blood pressure screeningmethods with consideration of rescreening intervals: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2015;162(3):192-204. doi:10.7326/M14-1539
11. Guirguis-Blake JM, Evans CV, Senger CA, O’Connor EA, Whitlock EP. Aspirin for the primary prevention of cardiovascular events: a systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. 2016;164(12):804-813. doi:10.7326/M15-2113
12. Chou R, Dana T, Blazina I, Daeges M, Jeanne TL. Statins for prevention of cardiovascular disease in adults: evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2016;316(19):2008-2024. doi:10.1001/jama.2015.15629
13. Patnode CD, Henderson JT, Thompson JH, Senger CA, Fortmann SP, Whitlock EP. Behavioral counseling and pharmacotherapy interventions for tobacco cessation in adults, including pregnant women: a review of reviews for the US Preventive Services Task Force. Ann Intern Med. 2015;163(8):608-621. doi:10.7326/M15-0171
14. US Preventive Services Task Force. U.S. Preventive Services Task Force Procedure Manual. Agency for Healthcare Research and Quality; 2015.
15. O’Connor EA, Evans CV, Rushkin MC, Redmond N, Lin JS. Behavioral Counseling Interventions to Promote a Healthful Diet and Physical Activity for Cardiovascular Disease Prevention in Adults With Cardiovascular Risk Factors: Updated Systematic Review for the U.S. Preventive Services Task Force. Evidence Synthesis No. 195. Agency for Healthcare Research and Quality; 2020. AHRQ publication 20-05263-EF-1.
16. Lin JS, O'Connor EA, Evans CV, Senger CA, Rowland MG, Groom HC. Behavioral Counseling to Promote a Healthy Lifestyle for Cardiovascular Disease Prevention in Persons With Cardiovascular Risk Factors: An Updated Systematic Evidence Review for the U.S. Preventive Services Task Force. Agency for Healthcare Research and Quality; 2014.
17. Patnode CD, Evans CV, Senger CA, Redmond N, Lin JS. Behavioral Counseling to Promote a Healthful Diet and Physical Activity for Cardiovascular Disease Prevention in Adults Without Known Cardiovascular Disease Risk Factors: Updated Systematic Review for the U.S. Preventive Services Task Force. Agency for Healthcare Research and Quality; 2017.
18. Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63(25, pt B):2935-2959. doi:10.1016/j.jacc.2013. 11.005
19. Wilson PW, D’Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation. 1998;97(18):1837-1847. doi:10.1161/01.CIR.97.18.1837
20. Human Development Report 2015:Work for Human Development. United Nations Development Programme. Published 2015. Accessed April 11, 2019. http://hdr.undp.org/sites/default/files/2015_human_development_report.pdf
21. Raudenbush SW. Analyzing effect sizes: random-effects models. In: Cooper H, Hedges LV, Valentine JC, eds. The Handbook of Research Synthesis and Meta-Analysis. 2nd ed. Russell Sage Foundation; 2009:296-314.
22. Knapp G, Hartung J. Improved tests for a random effects meta-regression with a single covariate. Stat Med. 2003;22(17):2693-2710. doi:10.1002/sim.1482
23. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629-634. doi:10.1136/bmj.315.7109.629
24. Berkman ND, Lohr KN, Ansari M, et al. Grading the strength of a body of evidence when assessing health care interventions for the effective health care program of the agency for healthcare research and quality: an update. In: Agency for Healthcare Research and Quality, eds. Methods Guide for Effectiveness and Comparative Effectiveness Reviews. Agency for Healthcare Research and Quality; 2014:314-349. AHRQ publication 10(14)-EHC063-EF.
25. Aadahl M, von Huth Smith L, Toft U, Pisinger C, Jørgensen T. Does a population-based multifactorial lifestyle intervention increase social inequality in physical activity? the Inter99 study. Br J Sports Med. 2011;45(3):209-215. doi:10.1136/bjsm.2009.064840
26. Agewall S, Fagerberg B, Berglund G, Schmidt C, Wendelhag I, Wikstrand J; Risk Factor Intervention Study Group, Sweden. Multiple risk intervention trial in high risk hypertensive men: comparison of ultrasound intima-media thickness and clinical outcome during 6 years of follow-up. J Intern Med. 2001;249(4):305-314. doi:10.1046/j.1365-2796.2001.00818.x
27. Agewall S, Fagerberg B, Samuelsson O, et al. Multiple cardiovascular risk factor intervention in treated hypertensive men: what can be achieved? Nutr Metab Cardiovasc Dis. 1993;3:128-135.
28. Agewall S, Wikstrand J, Dahlöf C, Fagerberg B. A randomized study of quality of life during multiple risk factor intervention in treated hypertensive men at high cardiovascular risk. J Hypertens. 1995;13(12, pt 1):1471-1477. doi:10.1097/00004872-199512000-00014
29. Agewall S, Wikstrand J, Samuelsson O, Persson B, Andersson OK, Fagerberg B; Risk Factor Intervention Study Group. The efficacy of multiple risk factor intervention in treated hypertensive men during long-term follow up. J Intern Med. 1994; 236(6):651-659. doi:10.1111/j.1365-2796.1994.tb00858.x
30. Ammerman AS, Keyserling TC, Atwood JR, Hosking JD, Zayed H, Krasny C. A randomized controlled trial of a public health nurse directed treatment program for rural patients with high blood cholesterol. Prev Med. 2003;36(3):340-351. doi:10.1016/S0091-7435(02)00042-7
31. Anderson JW, Garrity TF, Wood CL, Whitis SE, Smith BM, Oeltgen PR. Prospective, randomized, controlled comparison of the effects of low-fat and low-fat plus high-fiber diets on serum lipid concentrations. Am J Clin Nutr. 1992;56(5):887-894. doi:10.1093/ajcn/56.5.887
32. Anderssen S, Holme I, Urdal P, Hjermann I. Diet and exercise intervention have favourable effects on blood pressure in mild hypertensives: the Oslo Diet and Exercise Study (ODES). Blood Press. 1995;4(6):343-349. doi:10.3109/08037059509077619
33. Anderssen SA, Carroll S, Urdal P, Holme I. Combined diet and exercise intervention reverses the metabolic syndrome in middle-aged males: results from the Oslo Diet and Exercise Study. Scand J Med Sci Sports. 2007;17(6):687-695. doi:10.1111/j.1600-0838.2006.00631.x
34. Anderssen SA, Hjermann I, Urdal P, Torjesen PA, Holme I. Improved carbohydrate metabolism after physical training and dietary intervention in individuals with the"atherothrombogenic syndrome”: Oslo Diet and Exercise Study (ODES): a randomized trial. J Intern Med. 1996;240(4):203-209. doi:10.1046/j.1365-2796.1996.22848000.x
35. Anderssen SAH, Hjerman I, Urdal P, Gjesdal K, Holme I. Oslo diet and exercise study: a one year randomized intervention trial: effect on haemostatic variables and other coronary risk factors. Nutr Metab Cardiovasc Dis. 1995;5:189-200.
36. Appel LJ, Clark JM, Yeh HC, et al. Comparative effectiveness of weight-loss interventions in clinical practice. N Engl J Med. 2011;365(21):1959-1968. doi:10.1056/NEJMoa1108660
37. Appel LJ, Champagne CM, Harsha DW, et al; Writing Group of the PREMIER Collaborative Research Group. Effects of comprehensive lifestyle modification on blood pressure control: main results of the PREMIER clinical trial. JAMA. 2003;289(16):2083-2093.
38. Appel LJ, Espeland M, Whelton PK, et al. Trial of Nonpharmacologic Intervention in the Elderly (TONE): design and rationale of a blood pressure control trial. Ann Epidemiol. 1995;5(2):119-129. doi:10.1016/1047-2797(94)00056-Y
39. Appel LJ, Espeland MA, Easter L, Wilson AC, Folmar S, Lacy CR. Effects of reduced sodium intake on hypertension control in older individuals: results from the Trial of Nonpharmacologic Interventions in the Elderly (TONE). Arch Intern Med. 2001;161(5):685-693. doi:10.1001/archinte.161.5.685
40. Applegate WB, Miller ST, Elam JT, et al. Nonpharmacologic intervention to reduce blood pressure in older patients with mild hypertension. Arch Intern Med. 1992;152(6):1162-1166. doi:10.1001/archinte.1992.00400180034005
41. Arroll B, Beaglehole R. Salt restriction and physical activity in treated hypertensives. N Z Med J. 1995;108(1003):266-268.
42. Babazono A, Kame C, Ishihara R, Yamamoto E, Hillman AL. Patient-motivated prevention of lifestyle-related disease in Japan: a randomized, controlled clinical trial. Dis Manage Health Outcomes. 2007;15(2):119-126. doi:10.2165/00115677-200715020-00007
43. Babio N, Toledo E, Estruch R, et al; PREDIMED Study Investigators. Mediterranean diets and metabolic syndrome status in the PREDIMED randomized trial. CMAJ. 2014;186(17):E649-E657. doi:10.1503/cmaj.140764
44. Bahnson JL, Whelton PK, Appel LJ, et al. Baseline characteristics of randomized participants in the Trial of Nonpharmacologic Intervention in the Elderly (TONE). Dis Manag Clin Outcomes. 1997;1(2):61-68. doi:10.1016/S1088-3371(97)00005-3
45. Beckmann SL, Os I, Kjeldsen SE, Eide IK, Westheim AS, Hjermann I. Effect of dietary counselling on blood pressure and arterial plasma catecholamines in primary hypertension. Am J Hypertens. 1995;8(7):704-711. doi:10.1016/0895-7061(95)00122-6
46. Bennett GG, Steinberg D, Askew S, et al. Effectiveness of an app and provider counseling for obesity treatment in primary care. Am J Prev Med. 2018;55(6):777-786. doi:10.1016/j.amepre.2018.07.005
47. Bennett GG,Warner ET, Glasgow RE, et al; Be Fit, Be Well Study Investigators. Obesity treatment for socioeconomically disadvantaged patients in primary care practice. Arch Intern Med. 2012;172(7):565-574. doi:10.1001/archinternmed.2012.1
48. Beune EJ, Moll van Charante EP, Beem L, et al. Culturally adapted hypertension education (CAHE) to improve blood pressure control and treatment adherence in patients of African origin with uncontrolled hypertension: cluster-randomized trial. PLoS One. 2014;9(3):e90103. doi:10.1371/journal.pone.0090103
49. Blackford K, Jancey J, Lee AH, James A, Howat P, Waddell T. Effects of a home-based intervention on diet and physical activity behaviours for rural adults with or at risk of metabolic syndrome: a randomised controlled trial. Int J Behav Nutr Phys Act. 2016;13:13. doi:10.1186/s12966-016-0337-2
50. Blackford K, Jancey J, Lee AH, et al. A randomised controlled trial of a physical activity and nutrition program targeting middle-aged adults at risk of metabolic syndrome in a disadvantaged rural community. BMC Public Health. 2015;15:284. doi:10.1186/s12889-015-1613-9
51. Blackford K, Jancey J, Lee AH, James AP, Waddell T, Howat P. Home-based lifestyle intervention for rural adults improves metabolic syndrome parameters and cardiovascular risk factors: a randomised controlled trial. Prev Med. 2016;89:15-22. doi:10.1016/j.ypmed.2016.05.012
52. Blackford K, Lee A, James AP, et al. Process evaluation of the Albany Physical Activity and Nutrition (APAN) program, a home-based intervention for metabolic syndrome and associated chronic disease risk in rural Australian adults. Health Promot J Austr. 2017;28(1):8-14. doi:10.1071/HE16027
53. Bloemberg BP, Kromhout D, Goddijn HE, Jansen A, Obermann-de Boer GL. The impact of the Guidelines for a Healthy Diet of The Netherlands Nutrition Council on total and high-density lipoprotein cholesterol in hypercholesterolemic free-living men. Am J Epidemiol. 1991;134(1):39-48. doi:10.1093/oxfordjournals.aje.a115991
54. Blumenthal JA, BabyakMA, Hinderliter A, et al. Effects of the DASH diet alone and in combination with exercise and weight loss on blood pressure and cardiovascular biomarkers in men and women with high blood pressure: the ENCORE study. Arch Intern Med. 2010;170(2):126-135. doi:10.1001/archinternmed.2009.470
55. Bo S, Ciccone G, Baldi C, et al. Effectiveness of a lifestyle intervention on metabolic syndrome: a randomized controlled trial. J Gen Intern Med. 2007;22(12):1695-1703. doi:10.1007/s11606-007-0399-6
56. Bosworth HB, Olsen MK, Grubber JM, et al. Two self-management interventions to improve hypertension control: a randomized trial. Ann Intern Med. 2009;151(10):687-695. doi:10.7326/0000605-200911170-00148
57. Brantley PJ, Stewart DW, Myers VH, et al. Psychosocial predictors of weight regain in the weight loss maintenance trial. J Behav Med. 2014; 37(6):1155-1168. doi:10.1007/s10865-014-9565-6
58. Broekhuizen K, Jelsma JG, van Poppel MN, Koppes LL, Brug J, van Mechelen W. Is the process of delivery of an individually tailored lifestyle intervention associated with improvements in LDL cholesterol and multiple lifestyle behaviours in people with familial hypercholesterolemia? BMC Public Health. 2012;12:348. doi:10.1186/1471-2458-12-348
59. Broekhuizen K, van Poppel MN, Koppes LL, Brug J, van Mechelen W. A tailored lifestyle intervention to reduce the cardiovascular disease risk of individuals with familial hypercholesterolemia (FH): design of the PRO-FIT randomised controlled trial. BMC Public Health. 2010;10:69. doi:10.1186/1471-2458-10-69
60. Broekhuizen K, van Poppel MN, Koppes LL, Kindt I, Brug J, van Mechelen W. No significant improvement of cardiovascular disease risk indicators by a lifestyle intervention in people with familial hypercholesterolemia compared to usual care: results of a randomised controlled trial. BMC Res Notes. 2012;5:181. doi:10.1186/1756-0500-5-181
61. Broekhuizen K, van Poppel MN, Koppes LL, Kindt I, Brug J, van Mechelen W. Can multiple lifestyle behaviours be improved in people with familial hypercholesterolemia? results of a parallel randomised controlled trial. PLoS One. 2012;7(12):e50032. doi:10.1371/journal.pone.0050032
62. Bruckert E, Giral P, Paillard F, et al; PEGASE Group. Effect of an educational program (PEGASE) on cardiovascular risk in hypercholesterolaemic patients. Cardiovasc Drugs Ther. 2008;22(6):495-505. doi:10.1007/s10557-008-6137-4
63. Burke V, Beilin LJ, Cutt HE, Mansour J, Williams A, Mori TA. A lifestyle program for treated hypertensives improved health-related behaviors and cardiovascular risk factors, a randomized controlled trial. J Clin Epidemiol. 2007;60(2):133-141. doi:10.1016/j.jclinepi.2006.05.012
64. Burke V, Beilin LJ, Cutt HE, Mansour J, Mori TA. Moderators and mediators of behaviour change in a lifestyle program for treated hypertensives: a randomized controlled trial (ADAPT). Health Educ Res. 2008;23(4):583-591. doi:10.1093/her/cym047
65. Burke V, Beilin LJ, Cutt HE, Mansour J, Wilson A, Mori TA. Effects of a lifestyle programme on ambulatory blood pressure and drug dosage in treated hypertensive patients: a randomized controlled trial. J Hypertens. 2005;23(6):1241-1249. doi:10.1097/01.hjh.0000170388.61579.4f
66. Burke V, Mansour J, Beilin LJ, Mori TA. Long-term follow-up of participants in a health promotion program for treated hypertensives (ADAPT). Nutr Metab Cardiovasc Dis. 2008;18(3):198-206. doi:10.1016/j.numecd.2006.10.004
67. Camhi SM, Stefanick ML, Katzmarzyk PT, Young DR.Metabolic syndrome and changes in body fat from a low-fat diet and/or exercise randomized controlled trial. Obesity (Silver Spring). 2010;18(3):548-554. doi:10.1038/oby.2009.304
68. Champagne CM, Broyles ST, Moran LD, et al. Dietary intakes associated with successful weight loss and maintenance during theWeight Loss Maintenance Trial. J Am Diet Assoc. 2011;111(12):1826-1835. doi:10.1016/j.jada.2011.09.014
69. Chirinos DA, Goldberg RB, Llabre MM, et al. Lifestyle modification and weight reduction among low-income patients with the metabolic syndrome: the CHARMS randomized controlled trial. J Behav Med. 2016;39(3):483-492. doi:10.1007/s10865-016-9721-2
70. Christian JG, Byers TE, Christian KK, et al. A computer support program that helps clinicians provide patients with metabolic syndrome tailored counseling to promote weight loss. J Am Diet Assoc. 2011;111(1):75-83. doi:10.1016/j.jada.2010.10.006
71. Cicolini G, Simonetti V, Comparcini D, et al. Efficacy of a nurse-led email reminder program for cardiovascular prevention risk reduction in hypertensive patients: a randomized controlled trial. Int J Nurs Stud. 2014;51(6):833-843. doi:10.1016/j.ijnurstu.2013.10.010
72. Cochrane T, Davey R, Iqbal Z, et al. NHS health checks through general practice: randomised trial of population cardiovascular risk reduction. BMC Public Health. 2012;12:944. doi:10.1186/1471-2458-12-944
73. Cohen MD, D’Amico FJ, Merenstein JH. Weight reduction in obese hypertensive patients. Fam Med. 1991;23(1):25-28.
74. Coleman KJ, Farrell MA, Rocha DA, et al. Readiness to be physically active and self-reported physical activity in low-income Latinas, California WISEWOMAN, 2006-2007. Prev Chronic Dis. 2012;9:E87. doi:10.5888/pcd9.110190
75. Cook NR, Cutler JA, Obarzanek E, et al. Long term effects of dietary sodium reduction on cardiovascular disease outcomes: observational follow-up of the Trials of Hypertension Prevention (TOHP). BMJ. 2007;334(7599):885-888. doi:10.1136/bmj.39147.604896.55
76. Coughlin JW, Brantley PJ, Champagne CM, et al; Weight Loss Maintenance Collaborative Research Group. The impact of continued intervention on weight: five-year results from the Weight Loss Maintenance Trial. Obesity (Silver Spring). 2016;24(5):1046-1053. doi:10.1002/oby.21454
77. Crist LA, Champagne CM, Corsino L, Lien LF, Zhang G, Young DR. Influence of change in aerobic fitness and weight on prevalence of metabolic syndrome. Prev Chronic Dis. 2012;9:E68. doi:10.5888/pcd9.110171
78. Davey R, Cochrane T, Iqbal Z, et al. Randomised controlled trial of additional lifestyle support for the reduction of cardiovascular disease risk through primary care in Stoke-on-Trent, UK. Contemp Clin Trials. 2010;31(4):345-354. doi:10.1016/j.cct.2010.04.002
79. Davis BR, Blaufox MD, Hawkins CM, et al. Trial of antihypertensive interventions and management: design, methods, and selected baseline results. Control Clin Trials. 1989;10(1):11-30. doi:10.1016/0197-2456(89)90016-0
80. Delahanty LM, Sonnenberg LM, Hayden D, Nathan DM. Clinical and cost outcomes of medical nutrition therapy for hypercholesterolemia: a controlled trial. J Am Diet Assoc. 2001;101(9):1012-1023. doi:10.1016/S0002-8223(01)00250-4
81. Dolor RJ, YancyWS Jr, Owen WF, et al. Hypertension Improvement Project (HIP): study protocol and implementation challenges. Trials. 2009;10:13. doi:10.1186/1745-6215-10-13
82. Doménech M, Roman P, Lapetra J, et al. Mediterranean diet reduces 24-hour ambulatory blood pressure, blood glucose, and lipids: one-year randomized, clinical trial. Hypertension. 2014;64(1):69-76. doi:10.1161/HYPERTENSIONAHA.113.03353
83. Downer MK, Gea A, Stampfer M, et al. Predictors of short- and long-term adherence with a Mediterranean-type diet intervention: the PREDIMED randomized trial. Int J Behav Nutr Phys Act. 2016;13:67. doi:10.1186/s12966-016-0394-6
84. Driehuis F, Barte JC, Ter Bogt NC, et al. Maintenance of lifestyle changes: 3-year results of the Groningen Overweight and Lifestyle study. Patient Educ Couns. 2012;88(2):249-255. doi:10.1016/j.pec.2012.03.017
85. Drieling RL, Ma J, Stafford RS. Evaluating clinic and community-based lifestyle interventions for obesity reduction in a low-income Latino neighborhood: Vivamos Activos Fair Oaks Program. BMC Public Health. 2011;11:98. doi:10.1186/1471-2458-11-98
86. Eaglehouse YL, Rockette-Wagner B, Kramer MK, et al. Physical activity levels in a community lifestyle intervention: a randomized trial. Transl J Am Coll Sports Med. 2016;1(5):45-51.
87. Eakin E, Reeves M, Lawler S, et al. Telephone counseling for physical activity and diet in primary care patients. Am J Prev Med. 2009;36(2):142-149. doi:10.1016/j.amepre.2008.09.042
88. Eakin E, Reeves M, Winkler E, Lawler S, Owen N. Maintenance of physical activity and dietary change following a telephone-delivered intervention. Health Psychol. 2010;29(6):566-573. doi:10.1037/a0021359
89. Eakin EG, Reeves MM, Lawler SP, et al. The Logan Healthy Living Program: a cluster randomized trial of a telephone-delivered physical activity and dietary behavior intervention for primary care patients with type 2 diabetes or hypertension from a socially disadvantaged community—rationale, design and recruitment. Contemp Clin Trials. 2008;29(3):439-454. doi:10.1016/j.cct.2007.10.005
90. Edelman D, Oddone EZ, Liebowitz RS, et al. A multidimensional integrative medicine intervention to improve cardiovascular risk. J Gen Intern Med. 2006;21(7):728-734. doi:10.1111/j.1525-1497.2006.00495.x
91. Edwards RT, Linck P, Hounsome N, et al. Cost-effectiveness of a national exercise referral programme for primary care patients in Wales: results of a randomised controlled trial. BMC Public Health. 2013;13:1021. doi:10.1186/1471-2458-13-1021
92. Ellsworth DL, Costantino NS, Blackburn HL, Engler RJ, Kashani M, Vernalis MN. Lifestyle modification interventions differing in intensity and dietary stringency improve insulin resistance through changes in lipoprotein profiles. Obes Sci Pract. 2016;2(3):282-292. doi:10.1002/osp4.54
93. Elmer PJ, Obarzanek E, Vollmer WM, et al; PREMIER Collaborative Research Group. Effects of comprehensive lifestyle modification on diet, weight, physical fitness, and blood pressure control: 18-month results of a randomized trial. Ann Intern Med. 2006;144(7):485-495. doi:10.7326/0003-4819-144-7-200604040-00007
94. Espeland MA, Whelton PK, Kostis JB, et al; TONE Collaborative Research Group. Predictors and mediators of successful long-term withdrawal from antihypertensive medications. Arch Fam Med. 1999;8(3):228-236. doi:10.1001/archfami.8.3.228
95. Estruch R, Martínez-González MA, Corella D, et al; PREDIMED Study Investigators. Retracted: Effect of a high-fat Mediterranean diet on body weight and waist circumference: a prespecified secondary outcomes analysis of the PREDIMED randomised controlled trial. Lancet Diabetes Endocrinol. 2016;4(8):666-676. doi:10.1016/S2213-8587(16)30085-7
96. Estruch R, Martínez-González MA, Corella D, et al; PREDIMED Study Investigators. Effect of a high-fat Mediterranean diet on body weight and waist circumference: a prespecified secondary outcomes analysis of the PREDIMED randomised controlled trial. Lancet Diabetes Endocrinol. 2019;7(5):e6-e17. doi:10.1016/S2213-8587(19)30074-9
97. Estruch R, Ros E, Salas-Salvadó J, et al; PREDIMED Study Investigators. Primary prevention of cardiovascular disease with a Mediterranean diet supplemented with extra-virgin olive oil or nuts. N Engl J Med. 2018;378(25):e34. doi:10.1056/NEJMoa1800389
98. Estruch R, Ros E, Salas-Salvadó J, et al; PREDIMED Study Investigators. Primary prevention of cardiovascular disease with a Mediterranean diet [published corrections appear in N Engl J Med. 2014;370(9):886 and N Engl J Med. 2018;378(25):2441-2442]. N Engl J Med. 2013;368(14):1279-1290. doi:10.1056/NEJMoa1200303
99. Fagerberg B, Wikstrand J, Berglund G, Samuelsson O, Agewall S. Mortality rates in treated hypertensive men with additional risk factors are high but can be reduced: a randomized intervention study. Am J Hypertens. 1998;11(1, pt 1):14-22. doi:10.1016/S0895-7061(97)00363-4
100. Fanaian M, Laws RA, Passey M, et al. Health improvement and prevention study (HIPS)—evaluation of an intervention to prevent vascular disease in general practice. BMC Fam Pract. 2010;11:57. doi:10.1186/1471-2296-11-57
101. Farrell MA, Hayashi T, Loo RK, et al. Clinic-based nutrition and lifestyle counseling for Hispanic women delivered by community health workers: design of the California WISEWOMAN study. J Womens Health (Larchmt). 2009;18(5):733-739. doi:10.1089/jwh.2008.0871
102. Fernandez S, Tobin JN, Cassells A, Diaz-Gloster M, Kalida C, Ogedegbe G. The Counseling African Americans To Control Hypertension (CAATCH) trial: baseline demographic, clinical, psychosocial, and behavioral characteristics. Implement Sci. 2011;6:100. doi:10.1186/1748-5908-6-100
103. Foley P, Steinberg D, Levine E, et al. Track: a randomized controlled trial of a digital health obesity treatment intervention for medically vulnerable primary care patients. Contemp Clin Trials. 2016;48:12-20. doi:10.1016/j.cct.2016.03.006
104. Forsyth JM, Schoenthaler A, Ogedegbe G, Ravenell J. Perceived racial discrimination and adoption of health behaviors in hypertensive Black Americans: the CAATCH trial. J Health Care Poor Underserved. 2014;25(1):276-291. doi:10.1353/hpu.2014.0053
105. Friedberg JP, Rodriguez MA, Watsula ME, et al. Effectiveness of a tailored behavioral intervention to improve hypertension control: primary outcomes of a randomized controlled trial. Hypertension. 2015;65(2):440-446. doi:10.1161/HYPERTENSIONAHA.114.03483
106. From S, Liira H, Leppävuori J, Remes-Lyly T, Tikkanen H, Pitkälä K. Effectiveness of exercise intervention and health promotion on cardiovascular risk factors in middle-aged men: a protocol of a randomized controlled trial. BMC Public Health. 2013;13:125. doi:10.1186/1471-2458-13-125
107. Funk KL, Elmer PJ, Stevens VJ, et al. PREMIER—a trial of lifestyle interventions for blood pressure control: intervention design and rationale. Health Promot Pract. 2008;9(3):271-280. doi:10.1177/1524839906289035
108. Funk KL, Stevens VJ, Appel LJ, et al. Associations of internet website use with weight change in a long-term weight loss maintenance program. J Med Internet Res. 2010;12(3):e29. doi:10.2196/jmir.1504
109. Gill DP, Blunt W, Bartol C, et al. HealtheSteps™ study protocol: a pragmatic randomized controlled trial promoting active living and healthy lifestyles in at-risk Canadian adults delivered in primary care and community-based clinics. BMC Public Health. 2017;17(1):173. doi:10.1186/s12889-017-4047-8
110. Gill DP, Blunt W, Boa Sorte Silva NC, Stiller-Moldovan C, Zou GY, Petrella RJ. The HealtheSteps™ lifestyle prescription program to improve physical activity and modifiable risk factors for chronic disease: a pragmatic randomized controlled trial. BMC Public Health. 2019;19(1):841. doi:10.1186/s12889-019-7141-2
111. Gill R, Superko HR, McCarthy MM, et al. Cardiovascular risk factor reduction in first responders resulting from an individualized lifestyle and blood test program: a randomized controlled trial. J Occup Environ Med. 2019;61(3):183-189. doi:10.1097/JOM.0000000000001490
112. Gillison F, Greaves C, Stathi A, et al. “Waste the Waist”: the development of an intervention to promote changes in diet and physical activity for people with high cardiovascular risk. Br J Health Psychol. 2012;17(2):327-345. doi:10.1111/j.2044-8287.2011.02040.x
113. Gillison F, Stathi A, Reddy P, et al. Processes of behavior change and weight loss in a theory-based weight loss intervention program: a test of the process model for lifestyle behavior change. Int J Behav Nutr Phys Act. 2015;12(2):2. doi:10.1186/s12966-014-0160-6
114. Greaney ML, Quintiliani LM, Warner ET, et al. Weight management among patients at community health centers: the “Be Fit, Be Well” study. Obes Weight Manag. 2009;5(5):222-228. doi:10.1089/obe.2009.0507
115. Greaves C, Gillison F, Stathi A, et al. Waste the Waist: a pilot randomised controlled trial of a primary care based intervention to support lifestyle change in people with high cardiovascular risk. Int J Behav Nutr Phys Act. 2015;12:1. doi:10.1186/s12966-014-0159-z
116. Groeneveld IF, Proper KI, Absalah S, van der Beek AJ, van Mechelen W. An individually based lifestyle intervention for workers at risk for cardiovascular disease: a process evaluation. Am J Health Promot. 2011;25(6):396-401. doi:10.4278/ajhp.091001-QUAN-319
117. Groeneveld IF, Proper KI, van der Beek AJ, van Duivenbooden C, van Mechelen W. Design of a RCT evaluating the (cost-) effectiveness of a lifestyle intervention for male construction workers at risk for cardiovascular disease: the health under construction study. BMC Public Health. 2008;8:1. doi:10.1186/1471-2458-8-1
118. Groeneveld IF, Proper KI, van der Beek AJ, van Mechelen W. Sustained body weight reduction by an individual-based lifestyle intervention for workers in the construction industry at risk for cardiovascular disease: results of a randomized controlled trial. Prev Med. 2010;51(3-4):240-246. doi:10.1016/j.ypmed.2010.07.021
119. Haafkens JA, Beune EJ, Moll van Charante EP, Agyemang CO. A cluster-randomized controlled trial evaluating the effect of culturally-appropriate hypertension education among Afro-Surinamese and Ghanaian patients in Dutch general practice: study protocol. BMC Health Serv Res. 2009;9:193. doi:10.1186/1472-6963-9-193
120. Hansson L, Zanchetti A. The Hypertension Optimal Treatment (HOT) Study—patient characteristics: randomization, risk profiles, and early blood pressure results. Blood Press. 1994;3(5): 322-327. doi:10.3109/08037059409102281
121. Hardcastle S, Taylor A, Bailey M, Castle R. A randomised controlled trial on the effectiveness of a primary health care based counselling intervention on physical activity, diet and CHD risk factors. Patient Educ Couns. 2008;70(1):31-39. doi:10.1016/j.pec.2007.09.014
122. Hardcastle SJ, Taylor AH, Bailey MP, Harley RA, Hagger MS. Effectiveness of a motivational interviewing intervention on weight loss, physical activity and cardiovascular disease risk factors: a randomised controlled trial with a 12-month post-intervention follow-up. Int J Behav Nutr Phys Act. 2013;10:40. doi:10.1186/1479-5868-10-40
123. Harris MF, Fanaian M, Jayasinghe UW, et al. A cluster randomised controlled trial of vascular risk factor management in general practice. Med J Aust. 2012;197(7):387-393. doi:10.5694/mja12.10313
124. Haufe S, Kerling A, Protte G, et al. Telemonitoring-supported exercise training, metabolic syndrome severity, and work ability in company employees: a randomised controlled trial. Lancet Public Health. 2019;4(7):e343-e352. doi:10.1016/S2468-2667(19)30075-1
125. Hayashi T, Farrell MA, Chaput LA, Rocha DA, Hernandez M. Lifestyle intervention, behavioral changes, and improvement in cardiovascular risk profiles in the California WISEWOMAN project. J Womens Health (Larchmt). 2010;19(6):1129-1138. doi:10.1089/jwh.2009.1631
126. Hebert PR, Bolt RJ, Borhani NO, et al; Trials of Hypertension Prevention (TOHP) Collaborative Research Group. Design of a multicenter trial to evaluate long-term life-style intervention in adults with high-normal blood pressure levels. Ann Epidemiol. 1995;5(2):130-139. doi:10.1016/1047-2797(94)00057-Z
127. Hinderliter AL, Sherwood A, Craighead LW, et al. The long-term effects of lifestyle change on blood pressure: one-year follow-up of the ENCORE study. Am J Hypertens. 2014;27(5):734-741. doi:10.1093/ajh/hpt183
128. Hollis JF, Satterfield S, Smith F, et al; Trials of Hypertension Prevention (TOHP) Collaborative Research Group. Recruitment for phase II of the Trials of Hypertension Prevention: effective strategies and predictors of randomization. Ann Epidemiol. 1995;5(2):140-148. doi:10.1016/1047-2797(94)00058-2
129. von Huth Smith L, Ladelund S, Borch-Johnsen K, Jørgensen T. A randomized multifactorial intervention study for prevention of ischaemic heart disease (Inter99): the long-term effect on physical activity. Scand J Public Health. 2008;36(4):380-388. doi:10.1177/1403494807085313
130. Hyman DJ, Ho KS, Dunn JK, Simons-Morton D. Dietary intervention for cholesterol reduction in public clinic patients. Am J Prev Med. 1998;15(2):139-145. doi:10.1016/S0749-3797(98)00038-5
131. Hyman DJ, Pavlik VN, Taylor WC, Goodrick GK, Moye L. Simultaneous vs sequential counseling for multiple behavior change. Arch Intern Med. 2007;167(11):1152-1158. doi:10.1001/archinte.167.11.1152
132. Hypertension Prevention Trial Research Group. The Hypertension Prevention Trial: three-year effects of dietary changes on blood pressure. Arch Intern Med. 1990;150(1):153-162. doi:10.1001/archinte.1990.00390130131021
133. Ives DG, Kuller LH, Schulz R, Traven ND, Lave JR. Comparison of recruitment strategies and associated disease prevalence for health promotion in rural elderly. Prev Med. 1992;21(5):582-591. doi:10.1016/0091-7435(92)90066-Q
134. Ives DG, Kuller LH, Traven ND. Use and outcomes of a cholesterol-lowering intervention for rural elderly subjects. Am J Prev Med. 1993;9(5):274-281. doi:10.1016/S0749-3797(18)30703-7
135. Ives DG, Traven ND, Kuller LH, Schulz R. Selection bias and nonresponse to health promotion in older adults. Epidemiology. 1994;5(4):456-461. doi:10.1097/00001648-199407000- 00013
136. Jacobs DR Jr, Sluik D, Rokling-Andersen MH, Anderssen SA, Drevon CA. Association of 1-y changes in diet pattern with cardiovascular disease risk factors and adipokines: results from the 1-y randomized Oslo Diet and Exercise Study. Am J Clin Nutr. 2009;89(2):509-517. doi:10.3945/ajcn.2008.26371
137. Jerome GJ, Dalcin A, Coughlin JW, et al. Longitudinal accuracy of web-based self-reported weights: results from the Hopkins POWER Trial. J Med Internet Res. 2014;16(7):e173. doi:10.2196/jmir.3332
138. Johnston HJ, Jones M, Ridler-Dutton G, Spechler F, Stokes GS,Wyndham LE. Diet modification in lowering plasma cholesterol levels: a randomised trial of three types of intervention. Med J Aust. 1995;162(10):524-526. doi:10.5694/j.1326-5377.1995.tb138510.x
139. Jones DW, Miller ME, Wofford MR, et al. The effect of weight loss intervention on antihypertensive medication requirements in the Hypertension Optimal Treatment (HOT) study. Am J Hypertens. 1999;12(12, pt 1-2):1175-1180. doi:10.1016/S0895-7061(99)00123-5
140. Jørgensen T, Borch-Johnsen K, Thomsen TF, Ibsen H, Glümer C, Pisinger C. A randomized non-pharmacological intervention study for prevention of ischaemic heart disease: baseline results Inter99. Eur J Cardiovasc Prev Rehabil. 2003;10(5):377-386. doi:10.1097/01.hjr.0000096541.30533.82
141. Jørgensen T, Jacobsen RK, Toft U, Aadahl M, Glümer C, Pisinger C. Effect of screening and lifestyle counselling on incidence of ischaemic heart disease in general population: Inter99 randomised trial. BMJ. 2014;348:g3617. doi:10.1136/bmj.g3617
142. Kandula NR, Dave S, De Chavez PJ, et al. Translating a heart disease lifestyle intervention into the community: the South Asian Heart Lifestyle Intervention (SAHELI) study; a randomized control trial. BMC Public Health. 2015;15:1064. doi:10.1186/s12889-015-2401-2
143. Kandula NR, Patel Y, Dave S, et al. The South Asian Heart Lifestyle Intervention (SAHELI) study to improve cardiovascular risk factors in a community setting: design and methods. Contemp Clin Trials. 2013;36(2):479-487. doi:10.1016/j.cct. 2013.09.007
144. Kanke S, Kawai T, Takasawa N, Mashiyama Y, Ishii A, Kassai R. Interventions for body weight reduction in obese patients during short consultations: an open-label randomized controlled trial in the Japanese primary care setting. Asia Pac Fam Med. 2015;14(1):5. doi:10.1186/s12930-015-0022-7
145. Kastarinen MJ, Puska PM, Korhonen MH, et al; LIHEF Study Group. Non-pharmacological treatment of hypertension in primary health care: a 2-year open randomized controlled trial of lifestyle intervention against hypertension in eastern Finland. J Hypertens. 2002;20(12):2505-2512. doi:10.1097/00004872-200212000-00031
146. Keyserling TC, Ammerman AS, Atwood JR, et al. A cholesterol intervention program for public health nurses in the rural southeast: description of the intervention, study design, and baseline results. Public Health Nurs. 1999;16(3):156-167. doi:10.1046/j.1525-1446.1999.00156.x
147. Keyserling TC, Ammerman AS, Davis CE, Mok MC, Garrett J, Simpson R Jr. A randomized controlled trial of a physician-directed treatment program for low-income patients with high blood cholesterol: the Southeast Cholesterol Project. Arch Fam Med. 1997;6(2):135-145. doi:10.1001/archfami.6.2.135
148. Khanji MY, Balawon A, Boubertakh R, et al. Personalized E-coaching in cardiovascular risk reduction: a randomized controlled trial. Ann Glob Health. 2019;85(1):107. doi:10.5334/aogh.2496
149. Koelewijn-van Loon MS, van der Weijden T, van Steenkiste B, et al. Involving patients in cardiovascular risk management with nurse-led clinics: a cluster randomized controlled trial. CMAJ. 2009;181(12):E267-E274. doi:10.1503/cmaj.081591
150. Koelewijn-van Loon MS, van Steenkiste B, Ronda G, et al. Improving patient adherence to lifestyle advice (IMPALA): a cluster-randomised controlled trial on the implementation of a nurse-led intervention for cardiovascular risk management in primary care (protocol). BMC Health Serv Res. 2008;8:9. doi:10.1186/1472-6963-8-9
151. Korhonen M, Kastarinen M, Uusitupa M, Puska P, Nissinen A. The effect of intensified diet counseling on the diet of hypertensive subjects in primary health care: a 2-year open randomized controlled trial of lifestyle intervention against hypertension in eastern Finland. Prev Med. 2003;36(1):8-16. doi:10.1006/pmed.2002.1120
152. Kramer MK, Vanderwood KK, Arena VC, et al. Evaluation of a diabetes prevention program lifestyle intervention in older adults: a randomized controlled study in three senior/community centers of varying socioeconomic status. Diabetes Educ. 2018;44(2):118-129. doi:10.1177/0145721718759982
153. Kumanyika SK, Cook NR, Cutler JA, et al; Trials of Hypertension Prevention Collaborative Research Group. Sodium reduction for hypertension prevention in overweight adults: further results from the Trials of Hypertension Prevention phase II. J Hum Hypertens. 2005;19(1):33-45. doi:10.1038/sj. jhh.1001774
154. Kumanyika SK, Hebert PR, Cutler JA, et al; Trials of Hypertension Prevention Collaborative Research Group. Feasibility and efficacy of sodium reduction in the Trials of Hypertension Prevention, phase I. Hypertension. 1993;22(4):502-512. doi:10.1161/01.HYP.22.4.502
155. Lakerveld J, Bot SD, Chinapaw MJ, et al. Motivational interviewing and problem solving treatment to reduce type 2 diabetes and cardiovascular disease risk in real life: a randomized controlled trial. Int J Behav Nutr Phys Act. 2013;10:47. doi:10.1186/1479-5868-10-47
156. Lakerveld J, Bot SD, Chinapaw MJ, et al. Primary prevention of diabetes mellitus type 2 and cardiovascular diseases using a cognitive behavior program aimed at lifestyle changes in people at risk: design of a randomized controlled trial. BMC Endocr Disord. 2008;8:6. doi:10.1186/1472-6823-8-6
157. Lakerveld J, Bot SD, van der Ploeg HP, Nijpels G. The effects of a lifestyle intervention on leisure-time sedentary behaviors in adults at risk: the Hoorn Prevention Study, a randomized controlled trial. Prev Med. 2013;57(4):351-356. doi:10.1016/j.ypmed.2013.06.011
158. Langford HG, Davis BR, Blaufox D, et al; The TAIM Research Group. Effect of drug and diet treatment of mild hypertension on diastolic blood pressure. Hypertension. 1991;17(2):210-217. doi:10.1161/01.HYP.17.2.210
159. Lasser VI, Raczynski JM, Stevens VJ, et al; Trials of Hypertension Prevention (TOHP) Collaborative Research Group. Trials of Hypertension Prevention, phase II: structure and content of the weight loss and dietary sodium reduction interventions. Ann Epidemiol. 1995;5(2):156-164. doi:10.1016/1047-2797(94)00060-7
160. Lau C, Vistisen D, Toft U, et al. The effects of adding group-based lifestyle counselling to individual counselling on changes in plasma glucose levels in a randomized controlled trial: the Inter99 study. Diabetes Metab. 2011;37(6):546-552. doi:10.1016/j.diabet.2011.06.001
161. Lau CJ, Pisinger C, Husemoen LLN, et al. Effect of general health screening and lifestyle counselling on incidence of diabetes in general population: Inter99 randomised trial. Prev Med. 2016;91:172-179. doi:10.1016/j.ypmed.2016.08.016
162. Lawler SP, Winkler EA, Goode AD, Fjeldsoe BS, Reeves MM, Eakin EG. Moderators of health behavior initiation and maintenance in a randomized telephone counseling trial. Prev Med. 2014;61:34-41. doi:10.1016/j.ypmed.2014.01.002
163. Lee LL, Arthur A, Avis M. Evaluating a community-based walking intervention for hypertensive older people in Taiwan: a randomized controlled trial. Prev Med. 2007;44(2):160-166. doi:10.1016/j.ypmed.2006.09.001
164. Lien LF, Brown AJ, Ard JD, et al. Effects of PREMIER lifestyle modifications on participants with and without the metabolic syndrome. Hypertension. 2007;50(4):609-616. doi:10.1161/HYPERTENSIONAHA.107.089458
165. Liira H, Engberg E, Leppävuori J, et al. Exercise intervention and health checks for middle-aged men with elevated cardiovascular risk: a randomized controlled trial. Scand J Prim Health Care. 2014;32(4):156-162. doi:10.3109/02813432.2014.984967
166. Lin PH, Appel LJ, Funk K, et al. The PREMIER intervention helps participants follow the Dietary Approaches to Stop Hypertension dietary pattern and the current Dietary Reference Intakes recommendations. J Am Diet Assoc. 2007;107(9):1541-1551. doi:10.1016/j.jada.2007.06.019
167. Lin PH, Yancy WS Jr, Pollak KI, et al. The influence of a physician and patient intervention program on dietary intake. J Acad Nutr Diet. 2013;113(11):1465-1475. doi:10.1016/j.jand.2013.06.343
168. Littlecott HJ, Moore GF, Moore L, Murphy S. Psychosocial mediators of change in physical activity in theWelsh national exercise referral scheme: secondary analysis of a randomised controlled trial. Int J Behav Nutr Phys Act. 2014;11:109. doi:10.1186/s12966-014-0109-9
169. Martínez-González MA, Salas-Salvadó J, Estruch R, Corella D, Fitó M, Ros E; Predimed Investigators. Benefits of the Mediterranean Diet: Insights From the PREDIMED Study. Prog Cardiovasc Dis. 2015;58(1):50-60. doi:10.1016/j.pcad.2015.04.003
170. Martínez-González MA, Toledo E, Arós F, et al; PREDIMED Investigators. Extra virgin olive oil consumption reduces risk of atrial fibrillation: the PREDIMED (Prevención con Dieta Mediterránea) trial. Circulation. 2014;130(1):18-26. doi:10.1161/CIRCULATIONAHA.113.006921
171. Maruthur NM, Wang NY, Appel LJ. Lifestyle interventions reduce coronary heart disease risk: results from the PREMIER Trial. Circulation. 2009; 119(15):2026-2031. doi:10.1161/CIRCULATIONAHA.108.809491
172. McVay MA, King HA, Jeffreys AS, Coffman CJ, Voils CI. Mechanisms of patient health behavior change in a randomized controlled trial of a spouse-assisted intervention. Psychol Health Med. 2015;20(7):753-766. doi:10.1080/13548506.2015.1020817
173. Meinert CL, Borhani NO, Langford HG; Hypertension Prevention Trial Research Group. Design, methods, and rationale in the Hypertension Prevention Trial. Control Clin Trials. 1989;10(3)(suppl):1S-29S. doi:10.1016/0197-2456(89) 90040-8
174. Migneault JP, Dedier JJ, Wright JA, et al. A culturally adapted telecommunication system to improve physical activity, diet quality, and medication adherence among hypertensive African-Americans: a randomized controlled trial. Ann Behav Med. 2012;43(1):62-73. doi:10.1007/s12160-011-9319-4
175. Mitjavila MT, Fandos M, Salas-Salvadó J, et al. The Mediterranean diet improves the systemic lipid and DNA oxidative damage in metabolic syndrome individuals: a randomized, controlled, trial. Clin Nutr. 2013;32(2):172-178. doi:10.1016/j.clnu.2012.08.002
176. Moreau KL, Degarmo R, Langley J, et al. Increasing daily walking lowers blood pressure in postmenopausal women. Med Sci Sports Exerc. 2001;33(11):1825-1831. doi:10.1097/00005768-200111000-00005
177. Moy TF, Yanek LR, Raqueño JV, et al. Dietary counseling for high blood cholesterol in families at risk of coronary disease. Prev Cardiol. 2001;4(4):158-164. doi:10.1111/j.1520-037X.2001.00543.x
178. Mühlhauser I, Sawicki PT, Didjurgeit U, Jörgens V, Trampisch HJ, Berger M. Evaluation of a structured treatment and teaching programme on hypertension in general practice. Clin Exp Hypertens. 1993;15(1):125-142. doi:10.3109/10641969309041615
179. Murphy S, Raisanen L, Moore G, et al. A pragmatic randomised controlled trial of the Welsh National Exercise Referral Scheme: protocol for trial and integrated economic and process evaluation. BMC Public Health. 2010;10:352. doi:10.1186/1471-2458-10-352
180. Murphy SM, Edwards RT, Williams N, et al. An evaluation of the effectiveness and cost effectiveness of the National Exercise Referral Scheme inWales, UK: a randomised controlled trial of a public health policy initiative. J Epidemiol Community Health. 2012;66(8):745-753. doi:10.1136/jech-2011-200689
181. Neil HA, Roe L, Godlee RJ, et al. Randomised trial of lipid lowering dietary advice in general practice: the effects on serum lipids, lipoproteins, and antioxidants. BMJ. 1995;310(6979):569-573. doi:10.1136/bmj.310.6979.569
182. Niiranen TJ, Leino K, Puukka P, Kantola I, Karanko H, Jula AM. Lack of impact of a comprehensive intervention on hypertension in the primary care setting. Am J Hypertens. 2014;27(3):489-496. doi:10.1093/ajh/hpt204
183. Nolan RP, Feldman R, Dawes M, et al. Randomized controlled trial of E-counseling for hypertension: REACH. Circ Cardiovasc Qual Outcomes. 2018;11(7):e004420. doi:10.1161/CIRCOUTCOMES.117.004420
184. Nolan RP, Liu S, Feldman R, et al. Reducing risk with e-based support for adherence to lifestyle change in hypertension (REACH): protocol for a multicentred randomised controlled trial. BMJ Open. 2013;3(8):e003547. doi:10.1136/bmjopen-2013-003547
185. Oberman A,Wassertheil-Smoller S, Langford HG, et al. Pharmacologic and nutritional treatment of mild hypertension: changes in cardiovascular risk status. Ann Intern Med. 1990;112(2):89-95. doi:10.7326/0003-4819-112-2-89
186. Odes Investigators. The Oslo Diet and Exercise Study (ODES): design and objectives. Control Clin Trials. 1993;14(3):229-243. doi:10.1016/0197-2456(93)90005-X
187. Ogedegbe G, Tobin JN, Fernandez S, et al. Counseling African Americans to Control Hypertension: cluster-randomized clinical trial main effects. Circulation. 2014;129(20):2044-2051. doi 10.1161/CIRCULATIONAHA.113.006650
188. Ogedegbe G, Tobin JN, Fernandez S, et al. Counseling African Americans to Control Hypertension (CAATCH) trial: a multi-level intervention to improve blood pressure control in hypertensive blacks. Circ Cardiovasc Qual Outcomes. 2009;2(3):249-256. doi:10.1161/CIRCOUTCOMES.109.849976
189. Ponzo V, Gentile L, Gambino R, et al. Incidence of diabetes mellitus, cardiovascular outcomes and mortality after a 12-month lifestyle intervention: a 9-year follow-up. Diabetes Metab. 2018;44(5):449-451. doi:10.1016/j.diabet.2018.04.008
190. Reid RD, McDonnell LA, Riley DL, et al. Effect of an intervention to improve the cardiovascular health of family members of patients with coronary artery disease: a randomized trial. CMAJ. 2014;186(1):23-30. doi:10.1503/cmaj.130550
191. Reseland JE, Anderssen SA, Solvoll K, et al. Effect of long-term changes in diet and exercise on plasma leptin concentrations. Am J Clin Nutr. 2001; 73(2):240-245. doi:10.1093/ajcn/73.2.240
192. Rodríguez Cristóbal JJ, Alonso-Villaverde Grote C, Travé Mercadé P, et al; EFAP Group. Randomised clinical trial of an intensive intervention in the primary care setting of patients with high plasma fibrinogen in the primary prevention of cardiovascular disease. BMC Res Notes. 2012;5:126. doi:10.1186/1756-0500-5-126
193. Rodriguez MA. Is behavior change sustainable for diet, exercise, and medication adherence? Diss Abstr Int B Sci Eng. 2012;73(3-B):1860.
194. Rosas LG, Thiyagarajan S, Goldstein BA, et al. The effectiveness of two community-based weight loss strategies among obese, low-income US Latinos. J Acad Nutr Diet. 2015;115(4):537-50. doi:10.1016/j.jand.2014.10.020
195. Rubin RR, Peyrot M, Wang NY, et al. Patient-reported outcomes in the practice-based opportunities for weight reduction (POWER) trial. Qual Life Res. 2013;22(9):2389-2398. doi:10.1007/s11136-013-0363-3
196. Rubinstein A, Miranda JJ, Beratarrechea A, et al; GISMAL Group. Effectiveness of an mHealth intervention to improve the cardiometabolic profile of people with prehypertension in low-resource urban settings in Latin America: a randomised controlled trial. Lancet Diabetes Endocrinol. 2016;4(1):52-63. doi:10.1016/S2213-8587(15)00381-2
197. Ruiz-Canela M, Estruch R, Corella D, Salas-Salvadó J, Martínez-González MA. Association of Mediterranean diet with peripheral artery disease: the PREDIMED randomized trial. JAMA. 2014;311(4):415-417. doi:10.1001/jama.2013.280618
198. Salas-Salvadó J, Bulló M, Babio N, et al; PREDIMED Study Investigators. Erratum: reduction in the incidence of type 2 diabetes with the Mediterranean diet: results of the PREDIMED-Reus nutrition intervention randomized trial (Diabetes Care. 2011;34:14-19). Diabetes Care. 2018;41(10):2259-2260. doi:10.2337/dc18-er10
199. Salas-Salvadó J, Bulló M, Estruch R, et al. Prevention of diabetes with Mediterranean diets: a subgroup analysis of a randomized trial. Ann Intern Med. 2014;160(1):1-10. doi:10.7326/M13-1725
200. Salisbury C, O’Cathain A, Thomas C, et al. Telehealth for patients at high risk of cardiovascular disease: pragmatic randomised controlled trial. BMJ. 2016;353:i2647. doi:10.1136/bmj.i2647
201. Sarwer DB, Moore RH, Diewald LK, et al; POWER-UP Research Group. The impact of a primary care-based weight loss intervention on the quality of life. Int J Obes (Lond). 2013;37(suppl 1):S25-S30. doi:10.1038/ijo.2013.93
202. Satterfield S, Cutler JA, Langford HG, et al. Trials of hypertension prevention:phase I design. Ann Epidemiol. 1991;1(5):455-471. doi:10.1016/1047-2797(91)90014-4
203. Schoenthaler A, Luerassi L, Silver S, et al. Comparative effectiveness of a practice-based comprehensive lifestyle intervention vs. single session counseling in hypertensive blacks. Am J Hypertens. 2016;29(2):280-287. doi:10.1093/ajh/hpv100
204. Schoenthaler A, Luerassi L, Teresi JA, et al. A practice-based trial of blood pressure control in African Americans (TLC-Clinic): study protocol for a randomized controlled trial. Trials. 2011;12:265. doi:10.1186/1745-6215-12-265
205. Scott SE, Breckon JD, Copeland RJ. An integrated motivational interviewing and cognitive-behavioural intervention promoting physical activity maintenance for adults with chronic health conditions: a feasibility study. Chronic Illn. 2019;15(4):276-292. doi:10.1177/1742395318769370
206. Shah M, Jeffery RW, Laing B, Savre SG, Van Natta M, Strickland D; Hypertension Prevention Trial Research Group. Hypertension Prevention Trial (HPT): food pattern changes resulting from intervention on sodium, potassium, and energy intake. J Am Diet Assoc. 1990;90(1):69-76.
207. Soto Rodríguez A, García Soidán JL, de Toro Santos M, Lagoa Labrador F, Failde Garrido JM, Pérez Fernández MR. Benefits of an educational intervention on diet and anthropometric profile of women with one cardiovascular risk factor [in Spanish]. Med Clin (Barc). 2016;146(10):436-439. doi:10.1016/j.medcle.2016.06.047
208. Stefanick ML, Mackey S, Sheehan M, Ellsworth N, Haskell WL, Wood PD. Effects of diet and exercise in men and postmenopausal women with low levels of HDL cholesterol and high levels of LDL cholesterol. N Engl J Med. 1998;339(1):12-20. doi:10.1056/NEJM199807023390103
209. Stevens VJ, Corrigan SA, Obarzanek E, et al; TOHP Collaborative Research Group. Weight loss intervention in phase 1 of the Trials of Hypertension Prevention. Arch Intern Med. 1993;153(7):849-858. doi:10.1001/archinte.1993.00410070039006
210. Stevens VJ, Glasgow RE, Toobert DJ, Karanja N, Smith KS. One-year results from a brief, computer-assisted intervention to decrease consumption of fat and increase consumption of fruits and vegetables. Prev Med. 2003;36(5):594-600. doi:10.1016/S0091-7435(03)00019-7
211. Stevens VJ, Obarzanek E, Cook NR, et al; Trials for the Hypertension Prevention Research Group. Long-term weight loss and changes in blood pressure: results of the Trials of Hypertension Prevention, phase II. Ann Intern Med. 2001;134(1):1-11. doi:10.7326/0003-4819-134-1-200101020-00007
212. Svetkey LP, Ard JD, Stevens VJ, et al; Weight Loss Maintenance Collaborative Research Group. Predictors of long-term weight loss in adults with modest initial weight loss, by sex and race. Obesity (Silver Spring). 2012;20(9):1820-1828. doi:10.1038/oby.2011.88
213. Svetkey LP, Clark JM, Funk K, et al. Greater weight loss with increasing age in the weight loss maintenance trial. Obesity (Silver Spring). 2014;22(1):39-44. doi:10.1002/oby.20506
214. Svetkey LP, Erlinger TP, Vollmer WM, et al. Effect of lifestyle modifications on blood pressure by race, sex, hypertension status, and age. J Hum Hypertens. 2005;19(1):21-31. doi:10.1038/sj.jhh.1001770
215. Svetkey LP, Pollak KI, Yancy WS Jr, et al. Hypertension improvement project: randomized trial of quality improvement for physicians and lifestyle modification for patients. Hypertension. 2009;54(6):1226-1233. doi:10.1161/HYPERTENSIONAHA.109.134874
216. Svetkey LP, Stevens VJ, Brantley PJ, et al; Weight Loss Maintenance Collaborative Research Group. Comparison of strategies for sustaining weight loss: the weight loss maintenance randomized controlled trial. JAMA. 2008;299(10):1139-1148. doi:10.1001/jama.299.10.1139
217. ter Bogt NC, Bemelmans WJ, Beltman FW, Broer J, Smit AJ, van der Meer K. Preventing weight gain: one-year results of a randomized lifestyle intervention. Am J Prev Med. 2009;37(4):270-277. doi:10.1016/j.amepre.2009.06.011
218. ter Bogt NC, Milder IE, Bemelmans WJ, et al. Changes in lifestyle habits after counselling by nurse practitioners: 1-year results of the Groningen Overweight and Lifestyle Study. Public Health Nutr. 2011;14(6):995-1000. doi:10.1017/S1368980010003708
219. H.O.T. Study Group. The Hypertension Optimal Treatment Study (the HOT Study). Blood Press. 1993;2(1):62-68. doi:10.3109/08037059309077529
220. Trials of Hypertension Prevention Collaborative Research Group. The effects of nonpharmacologic interventions on blood pressure of persons with high normal levels: results of the Trials of Hypertension Prevention, phase I. JAMA. 1992;267(9):1213-1220. doi:10.1001/jama.1992.03480090061028
221. Trials of Hypertension Prevention Collaborative Research Group. Effects of weight loss and sodium reduction intervention on blood pressure and hypertension incidence in overweight people with high-normal blood pressure: the Trials of Hypertension Prevention, phase II. Arch Intern Med. 1997;157(6):657-667. doi:10.1001/archinte.1997.00440270105009
222. Thomas CL, Man MS, O’Cathain A, et al. Effectiveness and cost-effectiveness of a telehealth intervention to support the management of long-term conditions: study protocol for two linked randomized controlled trials. Trials. 2014;15:36. doi:10.1186/1745-6215-15-36
223. Tiessen AH, Smit AJ, Broer J, Groenier KH, van der Meer K. Randomized controlled trial on cardiovascular risk management by practice nurses supported by self-monitoring in primary care. BMC Fam Pract. 2012;13:90. doi:10.1186/1471-2296-13-90
224. Toft U, Kristoffersen L, Ladelund S, et al. The impact of a population-based multi-factorial lifestyle intervention on changes in long-term dietary habits: the Inter99 study. Prev Med. 2008;47(4):378-383. doi:10.1016/j.ypmed.2008.05.013
225. Toft U, Kristoffersen L, Ladelund S, et al. The effect of adding group-based counselling to individual lifestyle counselling on changes in dietary intake: the Inter99 study—a randomized controlled trial. Int J Behav Nutr Phys Act. 2008;5:59. doi:10.1186/1479-5868-5-59
226. Tomson Y, Aberg H. Risk factors for cardiovascular disease—a comparison between Swedes and immigrants. Scand J Prim Health Care. 1994;12(3):147-154. doi:10.3109/02813439409003691
227. Tomson Y, Johannesson M, Aberg H. The costs and effects of two different lipid intervention programmes in primary health care. J Intern Med. 1995;237(1):13-17. doi:10.1111/j.1365-2796.1995.tb01134.
228. Torjesen PA, Birkeland KI, Anderssen SA, Hjermann I, Holme I, Urdal P. Lifestyle changesmay reverse development of the insulin resistance syndrome: the Oslo Diet and Exercise Study: a randomized trial. Diabetes Care. 1997;20(1):26-31. doi:10.2337/diacare.20.1.26
229. van der Veen J, Bakx C, van den Hoogen H, et al. Stage-matched nutrition guidance for patients at elevated risk for cardiovascular disease: a randomized intervention study in family practice. J Fam Pract. 2002;51(9):751-758.
230. van Keulen HM, Bosmans JE, van Tulder MW, et al. Cost-effectiveness of tailored print communication, telephone motivational interviewing, and a combination of the two: results of an economic evaluation alongside the Vitalum randomized controlled trial. Int J Behav Nutr Phys Act. 2010;7(7):64. doi:10.1186/1479-5868-7-64
231. van Keulen HM, Mesters I, Ausems M, et al. Tailored print communication and telephone motivational interviewing are equally successful in improving multiple lifestyle behaviors in a randomized controlled trial. Ann Behav Med. 2011;41(1):104-118. doi:10.1007/s12160-010-9231-3
232. van Keulen HM, Mesters I, Brug J, et al. Vitalum study design: RCT evaluating the efficacy of tailored print communication and telephone motivational interviewing on multiple health behaviors. BMC Public Health. 2008;8:216. doi:10.1186/1471-2458-8-216
233. Van Sluijs EM, Van Poppel MN, Twisk JW, Brug J, Van Mechelen W. The positive effect on determinants of physical activity of a tailored, general practice-based physical activity intervention. Health Educ Res. 2005;20(3):345-356. doi:10.1093/her/cyg129
234. van Sluijs EM, van Poppel MN, Twisk JW, Chin A Paw MJ, Calfas KJ, van Mechelen W. Effect of a tailored physical activity intervention delivered in general practice settings: results of a randomized controlled trial. Am J Public Health. 2005;95(10):1825-1831. doi:10.2105/AJPH.2004.044537
235. Verheijden MW, Van der Veen JE, Bakx JC, et al. Stage-matched nutrition guidance: stages of change and fat consumption in Dutch patients at elevated cardiovascular risk. J Nutr Educ Behav. 2004;36(5):228-237. doi:10.1016/S1499-4046(06)60385-0
236. Vetter ML,Wadden TA, Chittams J, et al; POWER-UP Research Group. Effect of lifestyle intervention on cardiometabolic risk factors: results of the POWER-UP trial. Int J Obes (Lond). 2013;37(suppl 1):S19-S24. doi:10.1038/ijo.2013.92
237. Viglione C, Bouwman D, Rahman N, et al. A technology-assisted health coaching intervention vs. enhanced usual care for primary care-based obesity treatment: a randomized controlled trial. BMC Obes. 2019;6:4. doi:10.1186/s40608-018- 0226-0
238. Voils CI, Coffman CJ, Yancy WS Jr, et al. A randomized controlled trial to evaluate the effectiveness of CouPLES: a spouse-assisted lifestyle change intervention to improve low-density lipoprotein cholesterol. Prev Med. 2013;56(1):46-52. doi:10.1016/j.ypmed.2012.11.001
239. Voils CI, YancyWS Jr, Kovac S, et al. Study protocol: Couples Partnering for Lipid Enhancing Strategies (CouPLES)—a randomized, controlled trial. Trials. 2009;10:10. doi:10.1186/1745-6215-10-10
240. Volger S, Wadden TA, Sarwer DB, et al; POWER-UP Research Group. Changes in eating, physical activity and related behaviors in a primary care-based weight loss intervention. Int J Obes (Lond). 2013;37(suppl 1):S12-S18. doi:10.1038/ijo.2013.91
241. Wadden TA, Volger S, Sarwer DB, et al. A two-year randomized trial of obesity treatment in primary care practice. N Engl J Med. 2011;365(21):1969-1979. doi:10.1056/NEJMoa1109220
242. Whelton PK, Appel LJ, Espeland MA, et al; TONE Collaborative Research Group. Sodium reduction and weight loss in the treatment of hypertension in older persons: a randomized controlled trial of nonpharmacologic interventions in the elderly (TONE). JAMA. 1998;279(11):839-846. doi:10.1001/jama.279.11.839
243. Whelton PK, Hebert PR, Cutler J, et al. Baseline characteristics of participants in phase I of the Trials of Hypertension Prevention. Ann Epidemiol. 1992;2(3):295-310. doi:10.1016/1047-2797(92)90062-U
244. Wister A, Loewen N, Kennedy-Symonds H, McGowan B, McCoy B, Singer J. One-year follow-up of a therapeutic lifestyle intervention targeting cardiovascular disease risk. CMAJ. 2007;177(8):859-865. doi:10.1503/cmaj.061059
245. Wong MC, Wang HH, Kwan MW, et al. Dietary counselling has no effect on cardiovascular risk factors among Chinese grade 1 hypertensive patients: a randomized controlled trial. Eur Heart J. 2015;36(38):2598-2607. doi:10.1093/eurheartj/ehv329
246. Wong MCS, Wang HHX, Kwan MWM, et al. The effectiveness of Dietary Approaches to Stop Hypertension (DASH) counselling on estimated 10-year cardiovascular risk among patients with newly diagnosed grade 1 hypertension: a randomised clinical trial. Int J Cardiol. 2016;224:79-87. doi:10.1016/j.ijcard.2016.08.334
247. Wood DA, Kotseva K, Connolly S, et al; EUROACTION Study Group. Nurse-coordinated multidisciplinary, family-based cardiovascular disease prevention programme (EUROACTION) for patients with coronary heart disease and asymptomatic individuals at high risk of cardiovascular disease: a paired, cluster-randomised controlled trial. Lancet. 2008;371(9629):1999-2012. doi:10.1016/S0140-6736(08) 60868-5
248. Young DR, Coughlin J, Jerome GJ, Myers V, Chae SE, Brantley PJ. Effects of the PREMIER interventions on health-related quality of life. Ann Behav Med. 2010;40(3):302-312. doi:10.1007/s12160-010-9220-6
249. Young DR, Vollmer WM, King AC, et al. Can individuals meet multiple physical activity and dietary behavior goals? Am J Health Behav. 2009;33(3):277-286. doi:10.5993/AJHB.33.3.6
250. Yousuf H, Reintjens R, Slipszenko E, et al. Effectiveness of web-based personalised e-coaching lifestyle interventions. Neth Heart J. 2019;27(1):24-29. doi:10.1007/s12471-018-1200-7
251. Mensinger JL, Calogero RM, Stranges S, Tylka TL. A weight-neutral versus weight-loss approach for health promotion in women with high BMI: a randomized-controlled trial. Appetite. 2016; 105:364-374. doi:10.1016/j.appet.2016.06.006
252. Veronese N, Li Y, Manson JE, Willett WC, Fontana L, Hu FB. Combined associations of body weight and lifestyle factors with all cause and cause specific mortality in men and women: prospective cohort study. BMJ. 2016;355:i5855. doi:10.1136/ bmj.i5855
253. Li Y, Hruby A, Bernstein AM, et al. Saturated fats compared with unsaturated fats and sources of carbohydrates in relation to risk of coronary heart disease: a prospective cohort study. J Am Coll Cardiol. 2015;66(14):1538-1548. doi:10.1016/j.jacc.2015.07.055
254. Panizza CE, Shvetsov YB, Harmon BE, et al. Testing the predictive validity of the Healthy Eating Index–2015 in the multiethnic cohort: is the score associated with a reduced risk of all-cause and cause-specific mortality? Nutrients. 2018;10(4):452. doi:10.3390/nu10040
Evidence reviews for the US Preventive Services Task Force (USPSTF) use an analytic framework to visually display the key questions that the review will address to allow the USPSTF to evaluate the effectiveness and safety of a preventive service. The questions are depicted by linkages that relate interventions and outcomes. A dashed line indicates a health outcome that immediately follows an intermediate outcome. Details available in the USPSTF Procedure Manual.14 BMI indicates body mass index; BP, blood pressure; CVD, cardiovascular disease.
KQ indicates key question.
a Reasons for exclusion: Aim: Study aim not relevant. Setting: Study was not conducted in a country relevant to US practice or study was conducted in intermediate care facility or otherwise unrepresentative setting. Outcomes: Study did not report relevant outcomes. Population: Symptomatic, 50% or more with coronary heart disease or diabetes; 50% or more with prediabetes; age not 18 years or older. Intervention: Study used an excluded intervention or intervention aim was irrelevant. Study design: Not an included study design. Comparative effectiveness: follow-up 6 months or less. Quality: Study did not meet criteria for fair or good quality. Publication type: Ancillary study to excluded primary study.
CVD indicates cardiovascular disease; RR, risk ratio; TOHP I CRG, Trials of Hypertension Prevention–Phase I Collaborative Research Group; TOHP II CRG, Trials of Hypertension Prevention–Phase II Collaborative Research Group.
Random-effects restricted maximum likelihood model with Knapp-Hartung confidence intervals. Size of data markers indicates weight of each study in the analysis.
a Intervention contact time defined as low (0-30 minutes), medium (31-360 minutes), or high (>360 minutes).
b Hinderliter et al127 reported no CVD events in both groups (not shown on plot).
|Characteristics||Studies, No. (%)|
|All studies||Hypertensiona||Dyslipidemiab||Mixed risk factors|
|All studies||94 (100)||32 (100)||16 (100)||46 (10|
|RCT||78 (83.0)||27 (84.4)||11 (68.8)||40 (87.0)|
|Cluster RCT||16 (17.0)||5 (15.6)||5 (31.2)||6 (13.0)|
|Good quality ratingc||19 (20.2)||9 (28.1)||1 (6.2)||10 (21.7)|
|Conducted in the US||43 (45.7)||19 (59.4)||9 (56.2)||15 (32.6)|
|Primary care||38 (40.4)||12 (37.5)||5 (31.2)||21 (45.6)|
|Other health care||20 (21.3)||3 (9.4)||5 (31.2)||12 (26.1)|
|Other (eg, media, community settings, research center, epidemiologic surveys)||36 (38.3)||17 (53.1)||6 (37.5)||13 (28.3)|
|Multiple risk factors||46 (48.9)|
|Medication use restrictions|
|Limited to those taking medications to manage risk factors||11 (11.7)||9 (28.1)||0||2 (4.4)|
|Excluded those taking medications to manage risk factors||21 (22.3)||9 (28.1)||10 (62.5)||2 (4.4)|
|No restrictions||62 (66.0)||14 (43.8)||6 (37.5)||42 (91.3)|
|No intervention/ usual care||73 (77.7)||22 (68.8)||14 (87.5)||37 (80.4)|
|Minimal intervention||19 (20.2)||9 (28.1)||1 (6.2)||9 (19.6)|
|Attention control||2 (2.1)||1 (3.1)||1 (6.2)||0|
|Control group instructed to maintain typical habits||7 (7.4)||2 (6.3)||3 (18.8)||2 (4.4)|
|Sample size, median (IQR) [range]||314 (154-601) [24-7447]||272 (197-762) [24-2382]||222 (133-420) [80-1197]||342 (154-601) [37-7447]|
|Follow-up at 12 mo or closest, median (IQR) [range], %||86 (79-92) [63-100]||88 (80-92) [69-100]||88 (78-96) [73-99]||84 (78-91) [63-100]|
Abbreviations: IQR, interquartile range; RCT, randomized clinical trial; SBP, systolic blood pressure.
a Includes trials limited to persons with hypertension or elevated blood pressure.
b Includes trials limited to persons with dyslipidemia or elevated lipid levels.
c Twelve additional studies were rated as poor quality and excluded from the review; the remainder were rated fair quality.
|Outcome||Study population risk focus||Effect size (95% CI)a||No. of effects analyzed||No. of participants analyzed||I2, %||Median (IQR) change|
|Intervention group||Control group|
|SBP, mm Hg||All available trials||−1.81 (−2.49 to −1.13)||44||14,580||37.3||−5.1 (−7.6 to −1.7)||−2.9 (−6.0 to −0.2)|
|Hypertensionb||−1.97 (−2.59 to −1.36)||16||5769||7.8||−5.8 (−8.6 to −3.9)||−3.1 (−7.5 to −1.8)|
|DBP, mm Hg||All available trials||−1.16 (−1.57 to −0.75)||40||13,098||32.5||−3.4 (−4.6 to −0.7)||1.6 (−3.7 to −0.2)|
|Hypertensionb||−1.06 (−1.75 to −0.38||15||5461||43.4||−4.4 (−6.0 to −2.2)||−3.2 (−5.0 to −0.3)|
|Total cholesterol, mg/dL||All available trials||−3.48 (−5.57 to −1.38)||38||11,414||65.9||−7.1 (−12.4 to −2.3)||−4.4 (−6.6 to 0)|
|Dyslipidemiac||−3.80 (−7.23 to −0.37)||9||2001||24.0||−8.8 (−15.8 to −7.6)||−8.6 (−12.8 to −5.0|
|LDL-C, mg/dL||All available trials||−2.14 (−4.08 to −0.21)||32||8894||55.9||−4.8 (−11.2 to −1.5)||−3.9 (−7.7 to 0.1)|
|Dyslipidemiac||−4.12 (−8.81 to 0.57)||7||1271||36.3||−11.0 (−19.6 to −7.3)||−10.4 (−15.4 to −4.6)|
|HDL-C, mg/dL||All available trials||0.58 (0.19 to 0.98)||34||8974||33.7||0.8 (0.3 to 2.6)||0.5 (0 to 1.7)|
|Dyslipidemiac||−0.44 (−1.26 to 0.37)||6||1033||0.0||0.4 (0 to 3.1||1.0 (0.4 to 2.7)|
|Fasting blood glucose, mg/dL||All available trials||−2.33 (−3.64 to −1.02)||22||5950||82.5||−2.9 (−5.7 to −0.4)||0.2 (−2.0 to 3.6)|
|Weight, kg||All available trials||−1.59 (−2.06 to −1.12)||37||16,345||88.1||−1.5 (−2.8 to −0.8)||−0.3 (−1.0 to 0)|
|Weight loss trialsd||−2.55 (−3.40 to −1.70)||12||3193||66.9||−1.9 (−3.6 to −1.2)||−0.6 (−1.1 to 0)|
|BMIe||All available trials||−0.46 (−0.66 to −0.26)||30||9909||83.3||−0.5 (−0.9 to −0.2)||−0.1 (−0.4 to 0)|
|Weight loss trialsd||−0.91 (−1.43 to −0.40)||7||1520||78.0||−1.0 (−1.6 to −0.6)||−0.3 (−0.4 to −0.2)|
|Waist circumference, cm||All available trials||−1.75 (−2.44 to −1.06)||23||11,708||87.3||−2.2 (−3.7 to −0.8)||−0.9 (−1.8 to −0.2)|
|Weight loss trialsd||−2.50 (−3.97 to −1.03)||8||1654||85.4||−2.9 (−4.6 to −1.4)||−1.2 (−2.3 to −0.7)|
Abbreviations: BMI, body mass index; DBP, diastolic blood pressure; HDL-C, high-density lipoprotein cholesterol; IQR, interquartile range; LDL-C, low-density lipoprotein cholesterol.
SI conversion factors: To convert total cholesterol, LDL-C, and HDL-C values to mmol/L, multiply by 0.0259; fasting blood glucose values to mmol/L, multiply by 0.0555.
a Between-group mean difference in change unless otherwise specified.
b Includes trials limited to persons with hypertension or elevated blood pressure.
c Includes trials limited to persons with dyslipidemia or elevated lipid levels.
d Weight loss trials are those that required all participants to have a specified level of excess weight at baseline and had an explicit goal of weight loss for all participants.
e Calculated as weight in kilograms divided by height in meters squared.
|Outcome||Unit||Effect size (95% CI)a||No. of effects analyzed||No. of participants analyzed||I2, %||Median (IQR) change|
|Intervention group||Control group|
|Saturated fat||% of energy||−1.5 (−1.9 to −1.1)||15||6229||72||−1.9 (−3.0 to −1.4)||−0.6 (−1.0 to −0.1)|
|Saturated fat (fat-modified diet interventions only)||% of energy||−1.5 (−2.3 to −0.8)||8||3951||72||−2.2 (−3.0 to −1.6)||−0.5 (−1.0 to −0.01)|
|Polyunsaturated fat||% of energy||−0.4 (−1.0 to 0.3)||7||2032||90||−0.9 (−1.2 to −0.1)||0 (−0.3 to 0)|
|Monounsaturated fat||% of energy||−1.7 (−2.5 to −0.9)||7||1827||83||−2.0 (−2.1 to −1.9)||−0.2 (−0.4 to 0)|
|Fruits and vegetables||Servings/d||0.7 (0.1 to 1.3)||11||4310||90||0.5 (−0.01 to 1.2)||0.1 (0 to 0.3)|
|0.2 (0.04 to 0.3)||9||3698||71||0.2 (0.1 to 0.5)||0 (0 to 0.1)|
|Vegetables||Standardized mean difference||0.1 (0.02 to 0.2)||9||3555||50||Servings/d: 0.5 (0 to 0.8)||Servings/d: 0.3 (0.2 to 0.3)|
|g/d: 11 (9 to 16)||g/d: 2 (−3 to 12)|
|Fiber||g/d||1.3 (0.1 to 2.6)||5||1350||42||1.7 (0 to 3.0)||0.1 (−0.7 to 0.2)|
|Urinary sodium||mmol/L||−18.0 (−34.8 to −1.2)||9||3583||89||−18.4 (−45.4 to −5.3)||−6.0 (−10.0 to −3.4)|
|Physical activity||Standardized mean difference||0.06 (−0.03 to 0.14)||32||19,834||64||-||-|
|min/wk||9.1 (−4.6 to 22.8)||11||9746||48||44.4 (−2.5 to 97.0)||31.2 (−13.0 to 74.7)|
|MET-min/wk||83 (−83 to 249)||7||4958||62||130 (33 to 289)||70 (−16 to 112)|
|% Meeting physical activity goal||RR, 1.22 (1.00 to 1.50)||11||5887||91||36.0 (28.1 to 52.8)b||23.8 (22.9 to 50.8)b|
Abbreviations: IQR, interquartile range; MET, metabolic equivalent; RR, risk ratio.
a Between-group mean difference in change unless otherwise specified.
b Median (IQR) percent meeting physical activity goal.
No. of studies (No. of observations)
|Summary of findings||Consistency and precision||Other limitations||Strength of evidence||Applicability|
|KQ1: Benefits of interventions on CVD and related health outcomes|
|CVD events: 12 RCTs (15,107)
Mortality: 18 RCTs (18,146)
Subjective well-being: 11 RCTs (5684)
|CVD events were reported in 12 trials of medium- or high-contact interventions, and pooled analyses showed lower rates of total CVD events (pooled RR, 0.80 [95% CI, 0.73 to 0.87]; 9 studies) and fairly large but statistically nonsignificant associations with myocardial infarction (pooled RR, 0.85 [95% CI, 0.70 to 1.02]; 6 studies) and stroke (RR, 0.52 [95% CI, 0.25 to 1.10]; 4 studies)
Event rates were variable, but the largest trial reported that 3.6% of intervention participants had CVD events, compared with 4.4% of control participants
Few studies were powered for mortality; neither those few large studies nor the pooled estimate clearly demonstrated an effect on mortality (pooled RR, 0.89 [95% CI, 0.71 to 1.11])
Patient-reported measures of subjective well-being were sparsely reported and showed no clear pattern of clinically important benefit
|Mortality: Reasonably consistent, imprecise
CVD events: reasonably consistent, reasonably precise
Subjective well-being: nconsistent, imprecise
|Sparsely reported, few trials had sufficient power and length of follow-up for mortality and CVD events
Trial with the strongest evidence had protocol violations in allocation; however, extensive sensitivity analyses showed limited effect on results
|CVD events: moderate for benefit
Mortality: low for small to no benefit
|CVD events: Most trials conducted in the US; however, the largest trial providing the strongest evidence was conducted in Spain
Most participants across all trials were middle-aged and older adults who were predominantly White and not socioeconomically disadvantaged
|KQ2: Benefits of interventions on intermediate outcomes associated with CVD|
|Continuous clinical measures: 89 RCTs (46,354)
Hypertension incidence: 5 RCTs (2707)
Diabetes incidence: 4 RCTs (6701)
Metabolic syndrome: 5 RCTs (3103
|Behavioral counseling interventions were associated with small, statistically significant reductions in blood pressure,total cholesterol and LDL-C, fasting glucose, and adiposity-related outcomes at 12 to 24 mo follow-up
Hypertension incidence was lower with interventions designed to prevent hypertension in those who did not have it already (pooled RR, 0.74 [95% CI, 0.58 to 0.94]; 5 RCTs [n = 2707]; I2 = 12%)
No intervention factors were clearly associated with effect size, but among trials with the largest effects across multiple domains, most offered more than 6 h of intervention contact and many offered group as well as individual contact
Selected pooled mean differences:
Evidence primarily in medium- and high-contact interventions
|Reasonably consistent, reasonably precise||Hypertension prevalence, diabetes, and metabolic syndrome were reported in very few trials, raising concerns about reporting bias||High for benefit||Substantial number of trials conducted in the US and conducted in or recruited from primary care
Most participants across all trials were middle-aged and older adults who were predominantly White and not socioeconomically disadvantaged
|KQ3: Benefits of interventions in behavioral outcomes|
|70 RCTs (43,243)||Interventions were associated with small reductions in saturated fat and small increases in fruit, vegetable, and fiber consumption; for example, fruit and vegetables consumption increased by a mean of 0.7 servings/d more in the intervention than in the control groups (pooled mean difference, 0.7 [95% CI, 0.1 to 1.3]; 14 effects [11 RCTs] [n = 4310]; I2 = 90%)
The mean increase in fiber consumption was 1.3 g/d (95% CI, 0.1 to 2.6; 5 trials [n = 1350]; I2 = 42%)
In addition, trials of persons with hypertension or elevated blood pressure who were counseled to reduce sodium consumption showed greater reductions in urinary sodium (pooled mean difference, –18.0 [95% CI, –34.8 to –1.2]; 9 RCTs [n = 3583]; I2 = 89%)
Findings were mixed for physical activity
Most trials included medium- or high-contact intervention
|Diet: reasonably consistent, imprecise
Physical activity: inconsistent, imprecise
|Sparse reporting, with substantial variability in measures used, particularly for physical activity
Clinical importance of effect sizes could not be clearly determined
|Diet: low for benefit
Physical activity: low for no benefit
|Substantial number of trials conducted in the US and conducted in or recruited from primary care
Most participants across all trials were middle-aged and older adults who were predominantly White and not socioeconomically disadvantaged
|KQ4: Harms of interventions|
|20 RCTs (18,263)||Adverse events related to diet and physical activity counseling were very rare, with generally no statistically significant differences in any study for serious adverse events, any adverse events, hospitalizations, musculoskeletal injuries, withdrawals due to adverse events, gallbladder disease, and headaches
There was no consistent evidence of paradoxical effects for intermediate or behavioral outcomes
|Reasonably consistent, imprecise||Sparsely reported, ascertainment typically not described||Low for no harms||Substantial number of trials conducted in the US and conducted in or recruited from primary care
Abbreviations: BMI, body mass index; CVD, cardiovascular disease; DBP, diastolic blood pressure; KQ, key question; LDL-C, low-density lipoprotein cholesterol; RCT, randomized clinical trial; RR, risk ratio; SBP, systolic blood pressure.