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Effects of Lifestyle Modification on Psychosocial Function in Patients With Resistant Hypertension: SECONDARY OUTCOMES FROM THE TRIUMPH RANDOMIZED CLINICAL TRIAL.
Blumenthal, JA, Smith, PJ, Mabe, S, Hinderliter, A, Craighead, L, Watkins, LL, Ingle, K, Tyson, CC, Lin, PH, Kraus, WE, et al
Journal of cardiopulmonary rehabilitation and prevention. 2024;(1):64-70
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Abstract
PURPOSE In a secondary analysis of the TRIUMPH clinical trial, psychological outcomes in patients with resistant hypertension (RH) receiving a diet and exercise intervention delivered in a cardiac rehabilitation setting were compared with those receiving a similar prescription of diet and exercise provided in a single counseling session by a health educator. METHODS One hundred forty patients with RH were randomly assigned to a 4-mo program of dietary counseling, behavioral weight management, and exercise (C-LIFE) or a single counseling session providing standardized education and physician advice (SEPA). Participants completed a battery of questionnaires to assess psychological functioning before and after the intervention. A global measure of psychological functioning was derived from the General Health Questionnaire (GHQ), Perceived Stress Scale (PSS), Medical Outcomes Study 36-item Short Form Health Survey, Spielberger State-Trait Anxiety Inventory, Hospital Anxiety and Depression Scale (HADS), Beck Depression Inventory-II, and Patient-Reported Outcomes Measurement Information System (PROMIS) Anger scale. RESULTS Participants in the C-LIFE intervention achieved greater improvements in psychological functioning compared with SEPA (C-LIFE: 58.9 [56.1, 61.8] vs SEPA 66.5 [62.1, 70.9]; P = .024). Greater improvements were especially evident for the GHQ, PSS, and HADS. Examination of mediation revealed that greater weight loss ( B =-0.17, P = .004) and improved oxygen uptake ( B =-0.12, P = .044) were associated with improved psychological functioning. CONCLUSION Compared with standard education and physician advice, a structured program of diet and exercise not only reduced blood pressure but also improved psychological functioning in patients with RH.
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Inflammation moderates the effects of lifestyle modification on neurocognition among individuals with resistant hypertension.
Avorgbedor, F, Blumenthal, JA, Hinderliter, A, Ingle, K, Lin, PH, Craighead, L, Tyson, C, Kraus, W, Sherwood, A, Smith, PJ
Journal of clinical hypertension (Greenwich, Conn.). 2023;25(1):106-110
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Plain language summary
Hypertension is one of the primary causes of cardiovascular disease, stroke, Alzheimer’s Disease, and Alzheimer’s Disease and related dementias (AD/ADRD). Among individuals with hypertension, those with resistant hypertension (RH) appear to have the greatest risk of cerebrovascular disease and associated cognitive impairment. The aim of this study was to investigate the potential influence of individual differences in pre-treatment inflammatory profiles on changes in cognition following lifestyle modification among RH participants in the TRIUMPH clinical trial. This study is a report based on the TRIUMPH study which was a randomised clinical trial. One hundred forty patients with RH were randomised with 2:1 allocation to either a 4-month Centre-based Lifestyle intervention or Standardized Education and Physician Advice. Results show that basal levels of elevated peripheral inflammation may represent an intermediate phenotype of risk for cognitive decline. In fact, individuals with higher levels of c-reactive protein at baseline demonstrated greater improvements in Executive Function/Learning following participation in an intensive lifestyle intervention. Authors conclude that their findings may help inform targeted treatments to reduce ADRD among middle-aged and older adults with cardiovascular disease risk factors.
Abstract
Individuals with resistant hypertension (RH) have the greatest risk of cerebrovascular disease and cognitive impairment among individuals with hypertension. Elevated levels of pro-inflammatory cytokines may represent a critical yet unexamined factor influencing the impact of healthy lifestyle changes on cognitive function. We explored the influence of inflammation on changes in cognition following lifestyle modification among individuals with RH participating in the TRIUMPH clinical trial. One hundred forty participants with RH completed a battery of neurocognitive tests along with the inflammatory marker C-reactive protein (hsCRP) and were subsequently randomized to an intensive 4-month lifestyle modification intervention or to education and physician advice control. Results indicated that the effects of lifestyle modification on Executive Function and Learning were moderated by pre-intervention hsCRP levels (P = .049), with treatment efficacy increasing across levels of baseline inflammation levels (low: d = 0.12; mild: d = 0.43; moderate: d = 0.81). We conclude that inflammatory profiles may help identify individuals more likely to improve executive functioning resulting from lifestyle modification.
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Lifestyle Medicine as a Treatment for Resistant Hypertension.
Ribeiro, F, Teixeira, M, Alves, AJ, Sherwood, A, Blumenthal, JA
Current hypertension reports. 2023;(10):313-328
Abstract
PURPOSE OF REVIEW Approximately 10% of the adults with hypertension fail to achieve the recommended blood pressure treatment targets on 3 antihypertensive medications or require ≥ 4 medications to achieve goal. These patients with 'resistant hypertension' have an increased risk of target organ damage, adverse clinical events, and all-cause mortality. Although lifestyle modification is widely recommended as a first-line approach for the management of high blood pressure, the effects of lifestyle modifications in patients with resistant hypertension has not been widely studied. This review aims to provide an overview of the emerging evidence on the benefits of lifestyle modifications in patients with resistant hypertension, reviews potential mechanisms by which lifestyles may reduce blood pressure, and discusses the clinical implications of the recent findings in this field. RECENT FINDINGS Evidence from single-component randomized clinical trials demonstrated that aerobic exercise, weight loss and dietary modification can reduce clinic and ambulatory blood pressure in patients with resistant hypertension. Moreover, evidence from multi-component trials involving exercise and dietary modification and weight management can facilitate lifestyle change, reduce clinic and ambulatory blood pressure, and improve biomarkers of cardiovascular risk. This new evidence supports the efficacy of lifestyle modifications added to optimized medical therapy in reducing blood pressure and improving cardiovascular risk biomarkers in patients with resistant hypertension. These findings need to be confirmed in larger studies, and the persistence of benefit over extended follow-up needs further study.
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Exercise as a therapeutic modality for the prevention and treatment of depression.
Blumenthal, JA, Rozanski, A
Progress in cardiovascular diseases. 2023;:50-58
Abstract
While maintaining an active lifestyle and engaging in regular exercise are known to promote cardiovascular (CV) health, increasing evidence has emerged to indicate that these lifestyle behaviors also can promote psychological health and well-being. This has led to research to determine if exercise can serve as a potential therapeutic modality for major depressive disorder (MDD), which is a leading cause of mental-health impairment and overall disability worldwide. The strongest evidence to support this use comes from an increasing number of randomized clinical trials (RCTs) that have compared exercise to usual care, placebo controls, or established therapies in healthy adults and in various clinical populations. The relatively large number of RCTs has led to numerous reviews and meta-analyses, which generally have been concordant in indicating that exercise ameliorates depressive symptoms, improves self-esteem, and enhances various aspects of quality of life. Together, these data indicate that exercise should be considered as a therapeutic modality for improving CV health and psychological well-being. The emerging evidence also has led to a new proposed subspecialty of "lifestyle psychiatry", which promotes the use of exercise as an adjunctive treatment for patients with MDD. Indeed, some medical organizations have now endorsed lifestyle-based approaches as foundational aspects of depression management, with adoption of exercise as a treatment option for MDD. This review summarizes research in the area and provides practical suggestions for the use of exercise in clinical practice.
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Cardiology and lifestyle medicine.
Rozanski, A, Blumenthal, JA, Hinderliter, AL, Cole, S, Lavie, CJ
Progress in cardiovascular diseases. 2023;:4-13
Abstract
Poor lifestyle habits, such as physical inactivity and poor diets, are highly prevalent within society and even more so among patients with chronic disease. The need to stem poor lifestyle habits has led to the development of a new field of Lifestyle Medicine, whose mission is to prevent, treat, and even reverse chronic diseases through lifestyle interventions. Three fields within Cardiology relate to this mission: Cardiac Rehabilitation, Preventive Cardiology, and Behavioral Cardiology. Each of these three fields have contributed substantially to the reduction of cardiovascular disease (CVD) morbidity and mortality. The historic contributions of these three cardiac fields are reviewed as well as the challenges each of these fields has faced in optimizing the application of lifestyle medicine practices. A shared agenda between Cardiology and the American College of Lifestyle Medicine could further the utilization of behavioral interventions. This review suggests seven steps that could be shared by these organizations and other medical societies. First, there is a need to develop and promulgate the assessment of lifestyle factors as "vital signs" during patient visits. Second, developing a strong partnership between the fields of Cardiology and Physiatry could improve important aspects of cardiac care, including a potential redesign of cardiac stress testing. Third, behavioral evaluations should be optimized at patients' entrée points into medical care since these may be considered "windows of opportunity". Fourth, there is a need to broaden cardiac rehabilitation into inexpensive programs and make this program eligible for patients with risk factors but no known CVD. Fifth, lifestyle medicine education should be integrated into the core competencies for relevant specialties. Sixth, there is a need for inter-societal advocacy to promote lifestyle medicine practices. Seventh, the well-being effects of healthy lifestyle behaviors, such as their impact on one's sense of vitality, should be emphasized.
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Lifestyle modification and cognitive function among individuals with resistant hypertension: cognitive outcomes from the TRIUMPH trial.
Smith, PJ, Sherwood, A, Hinderliter, AL, Mabe, S, Watkins, LL, Craighead, L, Ingle, K, Tyson, C, Avorgbedor, F, Lin, PH, et al
Journal of hypertension. 2022;(7):1359-1368
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BACKGROUND Resistant hypertension is associated with increased risk of cognitive decline, stroke, and dementia. Lifestyle modification has been suggested to improve cognitive function through its salutary effects on vascular function. METHODS Participants included 140 patients with resistant hypertension participating in the TRIUMPH trial. Participants were randomized to a cardiac rehabilitation-based lifestyle program (C-LIFE) or a standardized education and physician advice condition (SEPA). Participants completed a 45-min cognitive test battery consisting of tests of Executive Functioning and Learning, Memory, and Processing Speed. Biomarkers of vascular [flow mediated dilation of the brachial artery (FMD)], microvascular, and cerebrovascular function were also collected, in addition to weight, fitness, and ambulatory blood pressure. RESULTS Participants averaged 63 years of age, 48% women, 59% black, and obese [mean BMI = 36 kg/m 2 (SD = 4)]. Cognitive performance improved across the entire cohort during the 4-month trial [ t -scores pretreatment = 48.9 (48, 50) vs. posttreatment = 50.0 (49, 51), P < 0.001]. Postintervention Executive Function/Learning composite performance was higher for participants in C-LIFE compared to SEPA ( d = 0.37, P = 0.039). C-LIFE intervention effects on Memory and Processing Speed were moderated by sex and baseline stroke risk, respectively ( P = 0.026 and P = 0.043 for interactions), such that males and participants with greater stroke risk showed the greatest cognitive changes. FMD [C-LIFE: +0.3% (-0.3, 1.0) vs. SEPA -1.4% (-2.5, -0.3), P = 0.022], and microvascular function [C-LIFE: 97 (65, 130) vs. SEPA 025 (-75, 23), P < 0.001] were improved in C-LIFE compared with SEPA, whereas cerebrovascular reactivity was not [C-LIFE: -0.2 (-0.4, 0) vs. SEPA 0.1 (-0.2, 0.4), P = 0.197). Mediation analyses suggested that increased executive function/learning was associated with reduced ambulatory SBP levels secondary to weight loss [indirect effect: B = 0.25 (0.03, 0.71)]. CONCLUSION Lifestyle modification individuals with resistant hypertension improves cognition, which appeared to be associated with reduced ambulatory SBP changes through weight loss. Cognitive improvements were accompanied by parallel improvements in endothelial and microvascular function.
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Effects of Lifestyle Modification on Patients With Resistant Hypertension: Results of the TRIUMPH Randomized Clinical Trial.
Blumenthal, JA, Hinderliter, AL, Smith, PJ, Mabe, S, Watkins, LL, Craighead, L, Ingle, K, Tyson, C, Lin, PH, Kraus, WE, et al
Circulation. 2021;(15):1212-1226
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BACKGROUND Although lifestyle modifications generally are effective in lowering blood pressure (BP) among patients with unmedicated hypertension and in those treated with 1 or 2 antihypertensive agents, the value of exercise and diet for lowering BP in patients with resistant hypertension is unknown. METHODS One hundred forty patients with resistant hypertension (mean age, 63 years; 48% female; 59% Black; 31% with diabetes; 21% with chronic kidney disease) were randomly assigned to a 4-month program of lifestyle modification (C-LIFE [Center-Based Lifestyle Intervention]) including dietary counseling, behavioral weight management, and exercise, or a single counseling session providing SEPA (Standardized Education and Physician Advice). The primary end point was clinic systolic BP; secondary end points included 24-hour ambulatory BP and select cardiovascular disease biomarkers including baroreflex sensitivity to quantify the influence of the baroreflex on heart rate, high-frequency heart rate variability to assess vagally mediated modulation of heart rate, flow-mediated dilation to evaluate endothelial function, pulse wave velocity to assess arterial stiffness, and left ventricular mass to characterize left ventricular structure. RESULTS Between-group comparisons revealed that the reduction in clinic systolic BP was greater in C-LIFE (-12.5 [95% CI, -14.9 to -10.2] mm Hg) compared with SEPA(-7.1 [-95% CI, 10.4 to -3.7] mm Hg) (P=0.005); 24-hour ambulatory systolic BP also was reduced in C-LIFE (-7.0 [95% CI, -8.5 to -4.0] mm Hg), with no change in SEPA (-0.3 [95% CI, -4.0 to 3.4] mm Hg) (P=0.001). Compared with SEPA, C-LIFE resulted in greater improvements in resting baroreflex sensitivity (2.3 ms/mm Hg [95% CI, 1.3 to 3.3] versus -1.1 ms/mm Hg [95% CI, -2.5 to 0.3]; P<0.001), high-frequency heart rate variability (0.4 ln ms2 [95% CI, 0.2 to 0.6] versus -0.2 ln ms2 [95% CI, -0.5 to 0.1]; P<0.001), and flow-mediated dilation (0.3% [95% CI, -0.3 to 1.0] versus -1.4% [95% CI, -2.5 to -0.3]; P=0.022). There were no between-group differences in pulse wave velocity (P=0.958) or left ventricular mass (P=0.596). CONCLUSIONS Diet and exercise can lower BP in patients with resistant hypertension. A 4-month structured program of diet and exercise as adjunctive therapy delivered in a cardiac rehabilitation setting results in significant reductions in clinic and ambulatory BP and improvement in selected cardiovascular disease biomarkers. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02342808.
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Carotid Intima-Media Thickness Progression as Surrogate Marker for Cardiovascular Risk: Meta-Analysis of 119 Clinical Trials Involving 100 667 Patients.
Willeit, P, Tschiderer, L, Allara, E, Reuber, K, Seekircher, L, Gao, L, Liao, X, Lonn, E, Gerstein, HC, Yusuf, S, et al
Circulation. 2020;(7):621-642
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BACKGROUND To quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk. METHODS We systematically collated data from randomized, controlled trials. cIMT was assessed as the mean value at the common-carotid-artery; if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were used. The primary outcome was a combined CVD end point defined as myocardial infarction, stroke, revascularization procedures, or fatal CVD. We estimated intervention effects on cIMT progression and incident CVD for each trial, before relating the 2 using a Bayesian meta-regression approach. RESULTS We analyzed data of 119 randomized, controlled trials involving 100 667 patients (mean age 62 years, 42% female). Over an average follow-up of 3.7 years, 12 038 patients developed the combined CVD end point. Across all interventions, each 10 μm/y reduction of cIMT progression resulted in a relative risk for CVD of 0.91 (95% Credible Interval, 0.87-0.94), with an additional relative risk for CVD of 0.92 (0.87-0.97) being achieved independent of cIMT progression. Taken together, we estimated that interventions reducing cIMT progression by 10, 20, 30, or 40 μm/y would yield relative risks of 0.84 (0.75-0.93), 0.76 (0.67-0.85), 0.69 (0.59-0.79), or 0.63 (0.52-0.74), respectively. Results were similar when grouping trials by type of intervention, time of conduct, time to ultrasound follow-up, availability of individual-participant data, primary versus secondary prevention trials, type of cIMT measurement, and proportion of female patients. CONCLUSIONS The extent of intervention effects on cIMT progression predicted the degree of CVD risk reduction. This provides a missing link supporting the usefulness of cIMT progression as a surrogate marker for CVD risk in clinical trials.
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Longer Term Effects of Diet and Exercise on Neurocognition: 1-Year Follow-up of the ENLIGHTEN Trial.
Blumenthal, JA, Smith, PJ, Mabe, S, Hinderliter, A, Welsh-Bohmer, K, Browndyke, JN, Doraiswamy, PM, Lin, PH, Kraus, WE, Burke, JR, et al
Journal of the American Geriatrics Society. 2020;(3):559-568
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OBJECTIVES To evaluate the longer term changes in executive functioning among participants with cardiovascular disease (CVD) risk factors and cognitive impairments with no dementia (CIND) randomized to a diet and exercise intervention. DESIGN A 2 (Exercise) × 2 (Dietary Approaches to Stop Hypertension [DASH] eating plan) factorial randomized clinical trial. SETTING Academic tertiary care medical center. PARTICIPANTS Volunteer sample of 160 older sedentary adults with CIND and at least one additional CVD risk factor enrolled in the ENLIGHTEN trial between December 2011 and March 2016. INTERVENTIONS Six months of aerobic exercise (AE), DASH diet counseling, combined AE + DASH, or health education (HE) controls. MEASUREMENTS Neurocognitive battery recommended by the Neuropsychological Working Group for Vascular Cognitive Disorders including measures of executive function, memory, and language/verbal fluency. Secondary outcomes included the Clinical Dementia Rating-Sum of Boxes (CDR-SB), Six-Minute Walk Distance (6MWD), and CVD risk including blood pressure, body weight, and CVD medication burden. RESULTS Despite discontinuation of lifestyle changes, participants in the exercise groups retained better executive function 1 year post-intervention (P = .041) compared with non-exercise groups, with a similar, albeit weaker, pattern in the DASH groups (P = .054), without variation over time (P's > .867). Participants in the exercise groups also achieved greater sustained improvements in 6MWD compared with non-Exercise participants (P < .001). Participants in the DASH groups exhibited lower CVD risk relative to non-DASH participants (P = .032); no differences in CVD risk were observed for participants in the Exercise groups compared with non-Exercise groups (P = .711). In post hoc analyses, the AE + DASH group had better performance on executive functioning (P < .001) and CDR-SB (P = .011) compared with HE controls. CONCLUSION For participants with CIND and CVD risk factors, exercise for 6 months promoted better executive functioning compared with non-exercisers through 1-year post-intervention, although its clinical significance is uncertain. J Am Geriatr Soc 68:559-568, 2020.
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Metabolic and Neurocognitive Changes Following Lifestyle Modification: Examination of Biomarkers from the ENLIGHTEN Randomized Clinical Trial.
Smith, PJ, Mabe, SM, Sherwood, A, Doraiswamy, PM, Welsh-Bohmer, KA, Burke, JR, Kraus, WE, Lin, PH, Browndyke, JN, Babyak, MA, et al
Journal of Alzheimer's disease : JAD. 2020;(4):1793-1803
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BACKGROUND Previous studies have demonstrated that aerobic exercise (AE) and the Dietary Approaches to Stop Hypertension (DASH) diet can improve neurocognition. However, the mechanisms by which lifestyle improves neurocognition have not been widely studied. We examined the associations between changes in metabolic, neurotrophic, and inflammatory biomarkers with executive functioning among participants from the Exercise and Nutritional Interventions for Neurocognitive Health Enhancement (ENLIGHTEN) trial. OBJECTIVE To examine the association between changes in metabolic function and neurocognition among older adults with cognitive impairment, but without dementia (CIND) participating in a comprehensive lifestyle intervention. METHODS ENLIGHTEN participants were randomized using a 2×2 factorial design to receive AE, DASH, both AE+DASH, or a health education control condition (HE) for six months. Metabolic biomarkers included insulin resistance (homeostatic model assessment [HOMA-IR]), leptin, and insulin-like growth factor (IGF-1); neurotrophic biomarkers included brain derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF); and inflammatory biomarkers included interleukin-6 (IL-6) and C-Reactive Protein (CRP). RESULTS Participants included 132 sedentary older adults (mean age = 65 [SD = 7]) with CIND. Results demonstrated that both AE (d = 0.48, p = 0.015) and DASH improved metabolic function (d = 0.37, p = 0.039), without comparable improvements in neurotrophic or inflammatory biomarkers. Greater improvements in metabolic function, including reduced HOMA-IR (B = -2.3 [-4.3, -0.2], p = 0.033) and increased IGF-1 (B = 3.4 [1.2, 5.7], p = 0.004), associated with increases in Executive Function. CONCLUSION Changes in neurocognition after lifestyle modification are associated with improved metabolic function.