Garrett I. Ash

The Promises and Challenges of the Use of Genomics in the Prescription of Exercise for Hypertension: The 2013 Update

Hypertension is a major global public health problem, resulting in over 7.6 million deaths per year (13.5% of the total), more than any other cardiovascular disease risk factor. Exercise decreases blood pressure (BP) 5-7 mmHg among those with hypertension. Thus, the American College of Sports Medicine recommends the exercise prescription (ExRx) of 30 min or more of moderate intensity, aerobic activity on most days of the week to lower BP. Yet, there is considerable individual variability in the BP response to exercise due to genetic and environmental factors that are poorly understood. We and others have shown there is a genetic component to the BP response to exercise accounting for a significant proportion of this variability. However, identification of specific genetic variants accounting for this variability is a significant challenge. This review describes new work on candidate gene and BP association studies. It also describes other important emerging work in genome wide association studies, next generation sequencing, epigenetics, and gene expression regulation, and how this work may have future relevance to ExRx for hypertension. The ultimate goal of our research is to use genetic information to personalize ExRx to optimize the effectiveness of exercise as a therapeutic modality for the prevention, treatment, and control of hypertension. Because of the complexities surrounding work in exercise genomics, the future use of genomics in ExRx for hypertension still remains a vision of the future rather than a reality of the present.

The blood pressure response to acute and chronic aerobic exercise: A meta-analysis of candidate gene association studies

OBJECTIVES To meta-analyze candidate gene association studies on the change in blood pressure beyond the immediate post-exercise phase after versus before aerobic exercise. DESIGN Meta-analysis. METHODS A systematic search was conducted. Studies retrieved included acute (short-term or postexercise hypotension) or chronic (long-term or training) aerobic exercise interventions; and blood pressure measured before and after aerobic exercise training, or before and after exercise or control under ambulatory conditions by genotype. Effect sizes were determined for genotype and adjusted for sample features. RESULTS Qualifying studies (k=17, n=3524) on average included middle-aged, overweight men (44.2%) and women (55.8%) with prehypertension (134.9±11.7/78.6±9.5mmHg). Training interventions (k=12) were performed at 60.4±12.9% of maximum oxygen consumption (VO2max) for 41.9±12.5minsession(-1), 3.6±1.2daysweek(-1) for 15.7±7.6week; and post-exercise hypotension interventions (k=5) were performed at 53.5±14.4% VO2max for 38.5±5.4minsession(-1). Sample characteristics explained 54.2-59.0% of the variability in the blood pressure change after versus before acute exercise or control under ambulatory conditions, and 57.4-67.1% of the variability in the blood pressure change after versus before training (p<0.001). Only angiotensinogen M235T (rs699) associated with the change in diastolic blood pressure after versus before training (R(2)=0.1%, p=0.05), but this association did not remain statistically significant after adjustment for multiple comparisons. CONCLUSIONS Sample characteristics explained most of the variability in the change of BP beyond the immediate post-exercise phase after versus before acute and chronic aerobic exercise. Angiotensinogen M235T (rs699) was the only genetic variant that associated with the change in diastolic blood pressure after versus before training, accounting for <1% of the variance.

Antihypertensive Effects of Exercise Among Those With Resistant Hypertension

Dimeo et al1 tested the hypothesis that aerobic exercise training reduces ambulatory blood pressure (ABP) among individuals with resistant hypertension and found that daytime systolic (6 mm Hg) and diastolic (3 mm Hg) ABPs were reduced after an 8- to 12-week aerobic exercise training program. Their findings indicate that exercise is effective antihypertensive therapy in a clinical population that is not responsive to drug therapy. Nonetheless, they should be interpreted with caution for the reasons below. Daytime ABP was the primary outcome. A complete description of the ABP methods including the timing when ABP was taken and procedures for handling missing …

Reproducibility of ambulatory blood pressure changes from the initial values on two different days

OBJECTIVE: We tested the reproducibility of changes in the ambulatory blood pressure (BP) from the initial values, an indicator of BP reactivity and cardiovascular health outcomes, in young, healthy adults. METHOD: The subjects wore an ambulatory BP monitor attached by the same investigator at the same time of day until the next morning on two different days (day 1 and day 2) separated by a week. We compared the ambulatory BP change from the initial values at hourly intervals over 24 waking and sleeping hours on days 1 and 2 using linear regression and repeated measures analysis of covariance. RESULTS: The subjects comprised 88 men and 57 women (mean age±SE 22.4±0.3 years) with normal BP (118.3±0.9/69.7±0.6 mmHg). For the total sample, the correlation between the ambulatory BP change on day 1 vs. day 2 over 24, waking, and sleeping hours ranged from 0.37–0.61; among women, the correlation was 0.38–0.71, and among men, it was 0.24–0.52. Among women, the ambulatory systolic/diastolic BP change was greater by 3.1±1.0/2.4±0.8 mmHg over 24 hours and by 3.0±1.1/2.4±0.8 mmHg over waking hours on day 1 than on day 2. The diastolic ambulatory BP change during sleeping hours was greater by 2.2±0.9 mmHg on day 1 than on day 2, but the systolic ambulatory BP change during sleeping hours on days 1 and 2 did not differ. Among men, the ambulatory BP change on days 1 and 2 did not differ. CONCLUSION: Our primary findings were that the ambulatory BP change from the initial values was moderately reproducible; however, it was more reproducible in men than in women. These results suggest that women, but not men, may experience an alerting reaction to initially wearing the ambulatory BP monitor.

The antihypertensive effects of aerobic versus isometric handgrip resistance exercise

Background: Aerobic exercise reduces blood pressure (BP) on average 5–7 mmHg among those with hypertension; limited evidence suggests similar or even greater BP benefits may result from isometric handgrip (IHG) resistance exercise. Method: We conducted a randomized controlled trial investigating the antihypertensive effects of an acute bout of aerobic compared with IHG exercise in the same individuals. Middle-aged adults (n = 27) with prehypertension and obesity randomly completed three experiments: aerobic (60% peak oxygen uptake, 30 min); IHG (30% maximum voluntary contraction, 4 × 2 min bilateral); and nonexercise control. Study participants were assessed for carotid-femoral pulse wave velocity pre and post exercise, and left the laboratory wearing an ambulatory BP monitor. Results: SBP and DBP were lower after aerobic versus IHG (4.8 ± 1.8/3.1 ± 1.3 mmHg, P = 0.01/0.04) and control (5.6 ± 1.8/3.6 ± 1.3 mmHg, P = 0.02/0.04) over the awake hours, with no difference between IHG versus control (P = 0.80/0.83). Pulse wave velocity changes following acute exercise did not differ by modality (aerobic increased 0.01 ± 0.21 ms, IHG decreased 0.06 ± 0.15 ms, control increased 0.25 ± 0.17 ms, P > 0.05). A subset of participants then completed either 8 weeks of aerobic or IHG training. Awake SBP was lower after versus before aerobic training (7.6 ± 3.1 mmHg, P = 0.02), whereas sleep DBP was higher after IHG training (7.7 ± 2.3 mmHg, P = 0.02). Conclusion: Our findings did not support IHG as antihypertensive therapy but that aerobic exercise should continue to be recommended as the primary exercise modality for its immediate and sustained BP benefits.

Effects of aerobic exercise intensity on ambulatory blood pressure and vascular responses in resistant hypertension: a crossover trial.

Background: Resistant hypertension often exposes patients to poor blood pressure (BP) control, resulting in clinical vulnerability, possible need for device-based procedures (denervation) and increased therapy costs. Regular exercise markedly benefits patients with hypertension, including resistant patients. However, little is known about short-term exercise effects in resistant hypertension. Objective: To evaluate acute hemodynamic effects of exercise in resistant hypertension. Method: After maximal exercise testing, 20 patients (54.0 ± 5.7 years, 30.2 ± 4.9 kg/m2) with resistant hypertension participated in three crossover interventions, in random order, and on separate days: control (45′ of rest), and light intensity and moderate intensity (45′ of aerobic exercise at 50 and 75% of maximum heart rate, respectively). Ambulatory BP, forearm blood flow (with subsequent calculation of vascular resistance), and reactive hyperemia were measured before and after interventions trough venous occlusion plethysmography. Results: Compared with control, both exercise intensities reduced ambulatory systolic pressure over 5 h (light: −7.7 ± 2.4 mmHg and moderate: −9.4 ± 2.8 mmHg, P < 0.01), whereas only light intensity reduced diastolic pressure (−5.7 ± 2.2 mmHg, P < 0.01). Light intensity also lowered systolic and diastolic pressures over 10-h daytime (−3.8 ± 1.3 and −4.0 ± 1.3 mmHg, respectively, P < 0.02), night-time (−6.0 ± 2.4 and −6.1 ± 1.6 mmHg, respectively, P < 0.05), and diastolic pressure over 19 h (−4.8 ± 1.2 mmHg, P < 0.01). Forearm blood flow changed (decreased) compared with baseline only at 50 min after light intensity (P < 0.05). After the control and light intensity sessions, vascular resistance increased at the end of 1 h, and after moderate intensity, it decreased only at the moment (∼2 min) immediately after intervention (P < 0.05). Conclusion: A single session of light or moderate aerobic exercise acutely reduces ambulatory BP in resistant hypertension, although benefits persist longer following light intensity.

Examination of Lifestyle Behaviors and Cardiometabolic Risk Factors in University Students Enrolled in Kinesiology Degree Programs

Abstract Many, GM, Lutsch, A, Connors, KE, Shearer, J, Brown, HC, Ash, G, Pescatello, LS, Gordish-Dressman, H, Barfield, W, Dubis, G, Houmard, JA, Hoffman, EP, and Hittel, DS. Examination of lifestyle behaviors and cardiometabolic risk factors in university students enrolled in kinesiology degree programs. J Strength Cond Res 30(4): 1137–1146, 2016—Preventing physical inactivity and weight gain during college is critical in decreasing lifelong obesity and associated disease risk. As such, we sought to compare cardiometabolic risk factors and lifestyle behaviors between college students enrolled in kinesiology and non-kinesiology degree programs to assess whether health and exercise degree programs may influence health behaviors and associated disease risk outcomes. Anthropometrics, fasting blood glucose, insulin, lipid profiles and HbA1c%, blood pressure, and peak oxygen consumption (V[Combining Dot Above]O2peak) were assessed in 247 healthy college students. The homeostasis model assessment of insulin sensitivity (HOMA) was calculated using glucose and insulin levels. Self-reported physical activity from the Paffenbarger questionnaire was collected to estimate the average caloric expenditure due to different types of physical activities. Despite no significant differences in body mass index or waist circumference between groups, kinesiology majors presented with ∼20% lower fasting insulin levels and HOMA (p = 0.01; p < 0.01, respectively) relative to nonmajors. Kinesiology majors reported increased weekly participation in vigorous-intensity sport and leisure activities and, on average, engaged in >300 metabolic equivalent-h·wk−1, whereas non-kinesiology majors engaged in <300 MET-h wk−1 (p = 0.01). Our data suggest that students enrolled in kinesiology degree programs display improved healthy behaviors and associated outcomes (parameters of glucose homeostasis). Practical outcomes of this research indicate that implementing components of a comprehensive kinesiology curriculum encourages improved health behaviors and associated cardiometabolic risk factors.

Glucocorticoid Receptor (NR3C1) Variants Associate with the Muscle Strength and Size Response to Resistance Training.

Glucocorticoid receptor (NR3C1) polymorphisms associate with obesity, muscle strength, and cortisol sensitivity. We examined associations among four NR3C1 polymorphisms and the muscle response to resistance training (RT). European-American adults (n = 602, 23.8±0.4yr) completed a 12 week unilateral arm RT program. Maximum voluntary contraction (MVC) assessed isometric strength (kg) and MRI assessed biceps size (cm2) pre- and post-resistance training. Subjects were genotyped for NR3C1 -2722G>A, -1887G>A, -1017T>C, and +363A>G. Men carrying the -2722G allele gained less relative MVC (17.3±1.2vs33.5±6.1%) (p = 0.010) than AA homozygotes; men with -1887GG gained greater relative MVC than A allele carriers (19.6±1.4vs13.2±2.3%) (p = 0.016). Women carrying the -1017T allele gained greater relative size (18.7±0.5vs16.1±0.9%) (p = 0.016) than CC homozygotes. We found sex-specific NR3C1 associations with the muscle strength and size response to RT. Future studies should investigate whether these associations are partially explained by cortisol’s actions in muscle tissue as they interact with sex differences in cortisol production.