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Background: Despite advances in surgery and pharmacotherapy, there remains significant residual ischemic risk after coronary artery bypass grafting surgery. Methods: In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial), a multicenter, placebo-controlled, double-blind trial, statin-treated patients with controlled low-density lipoprotein cholesterol and mild to moderate hypertriglyceridemia were randomized to 4 g daily of icosapent ethyl or placebo. They experienced a 25% reduction in risk of a primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina) and a 26% reduction in risk of a key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) when compared with placebo. The current analysis reports on the subgroup of patients from the trial with a history of coronary artery bypass grafting. Results: Of the 8179 patients randomized in REDUCE-IT, a total of 1837 (22.5%) had a history of coronary artery bypass grafting, with 897 patients randomized to icosapent ethyl and 940 to placebo. Baseline characteristics were similar between treatment groups. Randomization to icosapent ethyl was associated with a significant reduction in the primary end point (hazard ratio [HR], 0.76 [95% CI, 0.63–0.92]; P =0.004), in the key secondary end point (HR, 0.69 [95% CI, 0.56–0.87]; P =0.001), and in total (first plus subsequent or recurrent) ischemic events (rate ratio, 0.64 [95% CI, 0.50–0.81]; P =0.0002) compared with placebo. This yielded an absolute risk reduction of 6.2% (95% CI, 2.3%–10.2%) in first events, with a number needed to treat of 16 (95% CI, 10–44) during a median follow-up time of 4.8 years. Safety findings were similar to the overall study: beyond an increased rate of atrial fibrillation/flutter requiring hospitalization for at least 24 hours (5.0% vs 3.1%; P =0.03) and a nonsignificant increase in bleeding, occurrences of adverse events were comparable between groups. Conclusions: In REDUCE-IT patients with a history of coronary artery bypass grafting, treatment with icosapent ethyl was associated with significant reductions in first and recurrent ischemic events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01492361.

Caffeine has beneficial effects on firefighter job performance reducing fatigue and improving psychomotor vigilance. However, excessive caffeine intake may raise blood pressure (BP) following a bout of acute exercise among adults with elevated BP. The influence of caffeine intake on the ambulatory BP (ABP) response to vigorous physical exertion among firefighters has not been studied. In this sub-study we conducted secondary statistical analyses from a larger clinical trial (NCT04514354) that included examining the influence of habitual caffeine intake, and cardiometabolic biomarkers shown to influence BP, on the ABP response following a bout of sudden vigorous exertion over 19 h among firefighters. Previously, we found high amounts of calcium and sodium intake raised BP following a bout of acute exercise among adults with elevated BP. Thus, other secondary aims were to examine the influence of habitual calcium and sodium intake, and cardiometabolic biomarkers have shown to influence BP, on the ABP response following sudden vigorous exertion over 19 h among firefighters. Firefighters (n = 15) completed a Food-Frequency Questionnaire assessing habitual dietary intake over the past year. They randomly completed a maximal graded exercise stress test (GEST) and non-exercise CONTROL on separate non-workdays leaving the laboratory wearing an ABP monitor for 19 h. Prior to and immediately after the GEST, fasting venous blood was collected to measure lipid-lipoproteins, c-reactive protein, and blood glucose. Height and weight were taken to calculate body mass index. Repeated measures ANCOVA tested if the ABP response differed after GEST vs. CONTROL. Linear mixed models examined the relationships among caffeine, calcium, sodium, cardiometabolic biomarkers, and the ABP response following GEST vs. CONTROL. Firefighters were middle-aged (40.2 ± 9.5 year), overweight (29.0 ± 3.9 kg/m2) men with elevated BP (124.1 ± 10.3/79.6 ± 11.5 mmHg) who consumed 542.0 ± 348.9 mg of caffeine/day, about ~50% more than the dietary reference intake. Unexpectedly, systolic ABP was higher by 18.0 ± 6.7 mmHg and diastolic ABP by 9.1 ± 5.4 mmHg (ps < 0.01) over 19 h following GEST vs. CONTROL. We found 24% of the variance in the adverse ABP response to maximal physical exertion was explained by caffeine intake, and when combined with c-reactive protein, non-high-density lipoprotein-cholesterol, body mass index, blood glucose, and resting heart rate, up to 74% of the variability in the ABP response was explained. Additionally, we found calcium (ps < 0.001) and sodium (p < 0.0001) intake each explained up to 24% of the ABP response. Further investigation is needed in a larger, more diverse sample of firefighters to better establish how caffeine contributes to the adverse BP response to strenuous physical exertion.

Objective: To examine postexercise hypotension (PEH) after a maximal cardiopulmonary stress test (GEST) as well as heart rate variability (HRV), a surrogate marker of sympathovagal balance, as it relates to PEH among career firefighters with hypertension. Materials and Methods: Firefighters (n=5) who were middle-aged (40.6±6.2yr) and overweight (28.1±3.9kg.m-2) men with high BP (Systolic 126.4±9.5mmHg/Diastolic 85.6±5.9mmHg) and normal resting HR (71.1±11.2bpm) randomly performed a GEST and non-exercise control (CONTROL) session followed by attachment to ambulatory BP (ABP) and HR monitors for 19hr. Systolic (ASBP) and diastolic (ADBP) ABP, and HRV low (LF) and high (HF) frequency were recorded at hourly intervals over awake (11hr), sleep (8hr), and 19hr. Repeated measure analysis of variance (ANOVA) tested if BP and HRV differed over time and between experimental conditions. Multivariate regression tested the relationship between HRV and BP responses. Results: Compared to CONTROL, after the GEST ASBP significantly increased over awake (21.7±3.4mmHg, p=0.003) and 19hr (15.8±2.2mmHg, p=0.002), and exhibited a statistically trending increase over-sleep (7.9±2.9mmHg, p=0.055). Compared to CONTROL, after the GEST ADBP showed a statistically trending increase over awake (8.8±3.9 mmHg, p=0.091), sleep (8.2±4.3mmHg, p=0.134), and 19hr (8.6±3.5mmHg, p=0.072). Compared to CONTROL, after the GEST LF/HF significantly increased over awake (1.9±0.5, p=0.015), and displayed a statistically trending increase over 19hr (0.8±0.5 p=0.155). LF/HF statistically tended to explain up to 59.3% of the variance in the SBP response over 19hr (r:-0.77, p=0.068) and significantly explained 84.5% of the variance in the DBP response over awake (r:-0.92, p=0.014). Conclusion: Sudden vigorous exertion evoked postexercise hypertension as opposed to PEH among firefighters with elevated BP. Reasons for these unexpected findings are not clear but may reside in a compensatory baroreflex response to sympathetic predominance as reflected by higher LF/HF due to either increased sympathetic or decreased parasympathetic modulation.

Cardiovascular disease (CVD) risk factors cluster in an individual. Exercise is universally recommended to prevent and treat CVD. Yet, clinicians lack guidance on how to design an exercise prescription (ExRx) for patients with multiple CVD risk factors. To address this unmet need, we developed a novel clinical decision support system to prescribe exercise (prioritize personalize prescribe exercise [P3-EX]) for patients with multiple CVD risk factors founded upon the evidenced-based recommendations of the American College of Sports Medicine (ACSM) and American Heart Association. To develop P3-EX, we integrated (1) the ACSM exercise preparticipation health screening recommendations; (2) an adapted American Heart Association Life’s Simple 7 cardiovascular health scoring system; (3) adapted ACSM strategies for designing an ExRx for people with multiple CVD risk factors; and (4) the ACSM frequency, intensity, time, and time principle of ExRx. We have tested the clinical utility of P3-EX within a university-based online graduate program in ExRx among students that includes physicians, physical therapists, registered dietitians, exercise physiologists, kinesiologists, fitness industry professionals, and kinesiology educators in higher education. The support system P3-EX has proven to be an easy-to-use, guided, and time-efficient evidence-based approach to ExRx for patients with multiple CVD risk factors that has applicability to other chronic diseases and health conditions. Further evaluation is needed to better establish its feasibility, acceptability, and clinical utility as an ExRx tool.

Context:Compression socks have become increasingly popular with athletes due to perceived enhancement of exercise performance and recovery. However, research examining the efficacy of compression socks to reduce exercise-associated muscle damage has been equivocal, with few direct measurements of markers of muscle damage.Objective:To examine the influence of compression socks worn during a marathon on creatine kinase (CK) levels.Design:A randomized controlled trial.Setting:2013 Hartford Marathon, Hartford, CT.Participants:Adults (n = 20) randomized to control (CONTROL; n = 10) or compression sock (SOCK; n = 10) groups.Main Outcome Measures:Blood samples were collected 24 hours before, immediately after, and 24 hours following the marathon for the analysis of CK, a marker of muscle damage.Results:Baseline CK levels did not differ between CONTROL (89.3 [41.2] U/L) and SOCK (100.0 [56.2] U/L) (P = .63). Immediately following the marathon (≤1 h), CK increased 273% from baseline (P P = .60 for time × group). The day following the marathon (≤24 h), CK further increased 1094% from baseline (P P = .53 for time × group). These similar trends persisted despite controlling for potential covariates such as age, body mass index, and race finishing time (Ps > .29).Conclusions:Compression socks worn during a marathon do not appear to mitigate objectively measured markers of muscle damage immediately following and 24 hours after a marathon.

A single exercise session evokes immediate blood pressure (BP) reductions that persist for at least 24 h, termed postexercise hypotension (PEH). Self-monitoring of PEH may foster positive outcome expectations of exercise, and thus, enhance exercise adherence among adults with hypertension.To compare the efficacy of self-monitoring of exercise (EXERCISE) versus exercise and PEH (EXERCISE + PEH) to improve exercise adherence and BP control among adults with hypertension.Adults with high BP were randomized to EXERCISE (n = 12) or EXERCISE + PEH (n = 12). Participants underwent supervised, moderate intensity aerobic exercise training for 40-50 min/session, 3 days/week for 12 weeks and encouraged to exercise unsupervised at home at least 30 min/day, 1-2 days/week. EXERCISE + PEH also self-monitored BP before and after exercise. Adherence was calculated as [(no. of exercise sessions performed/no. of possible exercise sessions) × 100%]. BP was measured pre and posttraining.Healthy, middle-aged (52.3 ± 10.8 years) men (n = 11) and women (n = 13) with hypertension (136.2 ± 10.7/85.2 ± 8.9 mmHg) completed exercise training with 87.9 ± 12.1% adherence. EXERCISE + PEH demonstrated greater adherence to supervised training (94.3 ± 6.6%) than EXERCISE (81.6 ± 13.2%; P = 0.007). EXERCISE + PEH performed 32.6 ± 22.5 min/week more unsupervised home exercise than EXERCISE (P = 0.004), resulting in greater exercise adherence (107.3 ± 18.7%) than EXERCISE (82.7 ± 12.2%; P = 0.002). Post versus pretraining BP was reduced -7.4 ± 11.3/-4.9 ± 9.9 mmHg (P 0.025) with no statistical difference between EXERCISE (-5.2 ± 13.3/-3.6 ± 6.1 mmHg) and EXERCISE + PEH (-9.9 ± 11.3/-6.1 ± 6.9 mmHg; P 0.344).The current study is the first to demonstrate that PEH self-monitoring is an efficacious tool to improve exercise adherence among a small sample of adults with hypertension. Future research among a larger, more diverse sample is needed to confirm these novel findings and determine whether EXERCISE + PEH translates to better BP control relative to EXERCISE self-monitoring alone.

Venous thromboembolic (VTE) events such as deep vein thrombosis (DVT) and pulmonary embolism (PE) have been reported in otherwise low-risk healthy athletes following acute bouts of aerobic exercise.To review case reports and assess the commonalities of athletic individuals with VTE, as well as return-to-play (RTP) recommendations.We reviewed 47 reports (20 DVTs, 15 PEs, and 12 DVTs/PEs, 19 women) of trained individuals who were diagnosed with DVT and/or PE following aerobic exercise. We assessed frequency of VTE risk factors, presenting symptoms, and RTP recommendations.The age of women (24.6 ± 7.0 years) was lower (P .01) than of men (40.6 ± 13.6 years). Of the 19 women, 14 (73.7%) used oral contraceptives. Thirteen cases (27.7%) reported a recent period of prolonged inactivity (1 hour), and another 12 cases were found to have an antithrombin disorder following testing after diagnosis. The most frequently reported symptoms were muscle pain in 26 of 32 (81.3%) DVT or DVT/PE cases, and dyspnea in 21 of 27 (77.8%) PE or DVT/PE cases. Despite these common symptoms, the estimated time from first report of symptoms to confirmed diagnosis was 56.3 ± 118.7 days and 25 cases (53.2%) were initially misdiagnosed. Twenty-three cases (48.9%) did not report RTP recommendations, and those which did varied widely.Thirty-two cases (~70%) had at least one of three major risk factors, suggesting that many cases of VTE in athletes may be preventable with better education and awareness. The wide variety of RTP recommendations highlights the need for standardized guidelines in this population.

Insufficient 25-hydroxyvitamin D [25(OH)D] levels are associated with high resting blood pressure (BP). However, the relationship between 25(OH)D and the peak systolic BP (SBP) response to exercise, a predictor of future hypertension, has yet to be investigated. We sought to examine the relationship among serum 25(OH)D and the peak SBP response to a graded exercise stress test (GEST) among a large sample (n = 417) of healthy men (49%) and women (51%) over a broad age range (20–76 years; mean age: 44.1 ± 0.8 years). We hypothesized that individuals with clinically insufficient 25(OH)D would have a greater peak SBP response to a GEST compared to individuals with sufficient 25(OH)D levels. Fasting serum 25(OH)D, anthropometrics, resting BP, and peak exercise SBP were obtained at the baseline visit of a larger clinical trial (STOMP; NCT01140308). Mean 25(OH)D levels were 36.1 ± 0.7 ng/ml, with ∼35% of individuals classified as insufficient (p = 1.000). One unexpected finding emerged such that individuals with sufficient 25(OH)D had higher resting SBP (120 ± 14 mmHg vs. 117 ± 13 mmHg; p = .020) than individuals with insufficient 25(OH)D. In contrast to our hypothesis, 25(OH)D levels were not associated with the peak SBP response to a GEST. Baseline 25(OH)D levels were positively correlated with resting SBP; however, the magnitude of this effect is likely not clinically meaningful.

Heart rate variability (HRV) measurements via ambulatory monitors have become common. We examined the validity of recording R-R intervals using the Polar V800™ compared to 12-lead electrocardiograms (ECG) among middle-aged (44.7±10.1years); overweight to obese (29.8±4.3 kg.m-2) adults (n = 25) with hypertension (132.3±12.2/ 84.3±10.2 mmHg). After resting for 5-min in the supine position, R-R intervals were simultaneously recorded using the Polar V800™ and the 12-lead ECG. Artifacts present in uncorrected (UN) R-R intervals were corrected with the Kubios HRV Premium (ver. 3.2.) automatic (AC) and threshold-based (TBC) correction, and manual correction (MC) methods. Intra-class correlation coefficients (ICC), Bland-Altman limits of agreement (LoA), and effect sizes (ES) were calculated. We detected 71 errors with the Polar V800™ for an error rate of 0.85%. The bias (LoAs), ES, and ICC between UN and ECG R-R intervals were 0.69ms (-215.80 to +214.42ms), 0.004, and 0.79, respectively. Correction of artifacts improved the agreeability between the Polar V800™ and ECG HRV measures. The biases (LoAs) between the AC, TBC, and MC and ECG R-R intervals were 3.79ms (-130.32 to +137.90ms), 1.16ms (-92.67 to +94.98ms), and 0.37ms (-41.20 to +41.94ms), respectively. The ESs of AC, TBC, and MC were 0.024, 0.008, and 0.002, and ICCs were 0.91, 0.95, and 1.00, respectively. R-R intervals measured using the Polar V800™ compared to 12-lead ECG were comparable in adults with hypertension, especially after the artifacts corrected by MC. However, TBC correction also yielded acceptable results.

Hypertension (high blood pressure [BP]) is the most common, costly, and preventable cardiovascular disease risk factor in the world. Regular aerobic exercise is universally recommended as a lifestyle therapeutic intervention for the prevention, treatment, and control of high blood pressure. However, the stressor response to exercise in extreme but commonly experienced stressful environments may be exacerbated in individuals with hypertension, a situation not fully described in the literature. Therefore, we performed a systematic search examining the potential adverse health effects of exercising in hot, humid, cold, or air-polluted environments among adults with hypertension. Studies included adults with hypertension compared to normal BP and that with at least one physiological marker in response to heat, humidity, cold, windchill, or air pollution. The present systematic review revealed few studies that explored differences between individuals with hypertension and normal BP while exercising in commonly experienced stressful environmental conditions. Our preliminary evidence suggests that adults with hypertension may be more vulnerable to adverse cardiovascular stressor responses while exercising in the heat. Future studies are required to better characterize these maladaptive responses to extreme heat or humidity to better identify potential counter-measures for this vulnerable population.

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are extremely well tolerated but are associated with a range of mild-to-moderate statin-associated muscle symptoms (SAMS). Estimates of SAMS incidence vary from

Functional magnetic resonance imaging (fMRI) has not been used to assess the effects of statins on the brain. We assessed the effect of statins on cognition using standard neuropsychological assessments and brain neural activation with fMRI on two tasks.Healthy statin-naïve men and women (48±15 years) were randomized to 80 mg/day atorvastatin (n=66; 27 men) or placebo (n=84; 48 men) for 6 months. Participants completed cognitive testing while on study drug and 2 months after treatment cessation using alternative test and task versions.There were few changes in standard neuropsychological tests with drug treatment (all P.56). Total and delayed recall from the Hopkins Verbal Learning Test-Revised increased in both groups (P.05). The Stroop Color-Word score increased (P.01) and the 18-Point Clock Test decreased in the placebo group (P=.02) after drug cessation. There were, however, small but significant group-time interactions for each fMRI task: participants on placebo had greater activation in the right putamen/dorsal striatum during the maintenance phase of the Sternberg task while on placebo but the effect was reversed after drug washout (P.001). Participants on atorvastatin had greater activation in the bilateral precuneus during the encoding phase of the Figural Memory task while on-drug but the effect was reversed after drug washout (P.001).Six months of high dose atorvastatin therapy is not associated with measurable changes in neuropsychological test scores, but did evoke transient differences in brain activation patterns. Larger, longer-term clinical trials are necessary to confirm these findings and evaluate their clinical implications.

Considerable variability exists in the cardiometabolic disease biomarker response to exercise. We propose that a major contributor to this heterogeneity is underpowered studies due to small sample sizes. To test our hypothesis, we conducted a systematic review to identify meta-analyses/reviews of randomized controlled trials (RCT) and RCT that examined the cardiometabolic disease biomarker response to aerobic and resistance exercise.

Statins inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase, thereby reducing production of farnesyl pyrophosphate, an intermediate in the mevalonate pathway. The mevalonate pathway ultimately produces both cholesterol and coenzyme Q10 (CoQ10), a protein important for mitochondrial function. This knowledge has prompted the hypothesis that reductions in plasma CoQ10 concentrations contribute to statin-associated muscle symptoms (SAMS). Consequently, CoQ10 is popular as a form of adjuvant therapy for the treatment of SAMS. Clinical trial evidence evaluating the efficacy of CoQ10 supplementation has been equivocal. A meta-analysis suggests that CoQ10 supplementation is effective, but meta-analyses are dependent on the quality of the included studies and the best study did not demonstrate a CoQ10 benefit in subjects with verified SAMS. CoQ10 supplementation may be useful, however, perhaps as a placebo, in some patients.

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.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.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).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.

Aerobic exercise training and, to a lesser degree, dynamic resistance training, are recommended to lower blood pressure (BP) among adults with hypertension. Yet the combined influence of these exercise modalities, termed concurrent exercise training (CET), on resting BP is unclear.This study aimed to meta-analyze the literature to determine the efficacy of CET as antihypertensive therapy.Electronic databases were searched for trials that included the following: adults (19 yr), controlled CET interventions, and BP measured pre- and postintervention. Study quality was assessed with a modified Downs and Black Checklist. Analyses incorporated random-effects assumptions.Sixty-eight trials yielded 76 interventions. Subjects (N = 4110) were middle- to older-age (55.8 ± 14.4 yr), were overweight (28.0 ± 3.6 kg·m), and had prehypertension (systolic BP [SBP]/diastolic BP [DBP] = 134.6 ± 10.9/80.7 ± 7.5 mm Hg). CET was performed at moderate intensity (aerobic = 55% maximal oxygen consumption, resistance = 60% one-repetition maximum), 2.9 ± 0.7 d·wk for 58.3 ± 20.1 min per session for 19.7 ± 17.8 wk. Studies were of moderate quality, satisfying 60.7% ± 9.4% of quality items. Overall, CET moderately reduced SBP (db = -0.32, 95% confidence interval [CI] = -0.44 to -0.20, -3.2 mm Hg) and DBP (db = -0.35, 95% CI = -0.47 to -0.22, -2.5 mm Hg) versus control (P0.01). However, greater SBP/DBP reductions were observed among samples with hypertension in trials of higher study quality that also examined BP as the primary outcome (-9.2 mm Hg [95% CI = -12.0 to -8.0]/-7.7 mm Hg [95% CI = -14.0 to -8.0]).Among samples with hypertension in trials of higher study quality, CET rivals aerobic exercise training as antihypertensive therapy. Because of the moderate quality of this literature, additional randomized controlled CET trials that examine BP as a primary outcome among samples with hypertension are warranted to confirm our promising findings.

Marathon running exposes athletes to thrombogenic risk factors that increase blood clot risk in otherwise healthy athletes. Understanding the effect of these factors on coagulation and fibrinolysis can aid both the practitioner and athlete in primary and secondary prevention of venous thromboembolism. Accordingly, the purpose of the present review is to synthesize evidence surrounding athlete specific risk for venous thromboembolism.

BackgroundThere is a high prevalence of cardiovascular disease across diverse groups in the U.S. population, and increasing research has identified stigma as a potential barrier to cardiovascular disease prevention and treatment. This systematic review examines evidence linking discrimination and cardiovascular health among socially stigmatized groups.Study designSix databases were systematically reviewed from inception through February 2018 for studies with adult subjects, focusing on cardiovascular health indicators among social groups stigmatized because of their gender, race/ethnicity, age, body weight/obesity, or sexual orientation. The Newcastle-Ottawa Scale was used to evaluate the methodological quality and risk of bias for nonrandomized studies, and the Cochrane Collaboration 7-item domain for randomized controlled and experimental trials.ResultsThe search identified 84 eligible studies published between 1984 and 2017. Studies retrieved were categorized according to demonstrated links between stigma and cardiovascular disease risk factors including blood pressure (n = 45), heart rate variability (n = 6), blood/saliva cardiovascular biomarkers (n = 18), as well as other indicators of cardiovascular health (n = 15). Based on the findings from included studies, 86% concluded that there was a significant relationship among stigma or discrimination and cardiovascular health indicators among socially stigmatized groups. However, there were varying degrees of evidence supporting these relationships, depending on the type of discrimination and cardiovascular health indicator. The current evidence implies an association between perceived discrimination and cardiovascular health. However, a majority of these studies are cross-sectional (73%) and focus on racial discrimination (79%), while using a wide variety of measurements to assess social discrimination and cardiovascular health.ConclusionsFuture research should include longitudinal and randomized controlled trial designs, with larger and more diverse samples of individuals with stigmatized identities, using consistent measurement approaches to assess social discrimination and its relationship with cardiovascular health.

Adverse alterations in the skeletal muscle response to exercise have been noted among adults with hypertension. The influence of resting blood pressure (BP) on muscle strength is unknown. We hypothesized that adults with high BP would exhibit lower muscular strength than adults with normal BP. An isokinetic dynamometer tested 21 measures of isometric and isokinetic muscle strength. BP was measured by auscultation. Patients were categorized into having normal (120 and80 mmHg) or high (≥120 and/or ≥80 mmHg) BP. Height (cm) and weight (kg) were measured to calculate BMI (kg/m). Analysis of covariance tested differences in muscle strength between BP groups with sex, age, and height as covariates. Patients [420 (49%) men] were middle-aged (44.1±16.1 years) and overweight (26.4±4.8 kg/m) with 187 having normal (107.7±7.3/68.3±6.3 mmHg) and 233 having high (127.8±9.8/80.8±8.1 mmHg) BP. For upper body, three of five extension measures and five of five flexion measures, as well as handgrip, were greater in the high than the normal BP group (P≤0.05). For lower body, five of five extension measures were greater in the high than the normal BP group, whereas there were no differences between BP groups for the five flexion measures (P0.05). Contrary to our hypothesis, adults with high BP displayed greater muscle strength than adults with normal BP. Reasons for our findings are unclear, but may be because of shifts in muscle fiber type from type I to type IIb/x and oxidative to glycolytic metabolism; alterations may result in a more strength-adapted phenotype among adults with high BP such as we observed.

Objectives To examine the effects of exercise training on cognitive function in individuals at risk of or diagnosed with Alzheimer's disease (AD). Design Meta‐analysis. Setting PubMed, Scopus, ClinicalTrials.gov, and ProQuest were searched from inception until August 1, 2017. Participants Nineteen studies with 23 interventions including 1,145 subjects with a mean age of 77.0 ± 7.5 were included. Most subjects were at risk of AD because they had mild cognitive impairment (64%) or a parent diagnosed with AD (1%), and 35% presented with AD. Intervention Controlled studies that included an exercise‐only intervention and a nondiet, nonexercise control group and reported pre‐ and post‐intervention cognitive function measurements. Measurements Cognitive function before and after the intervention and features of the exercise intervention. Results Exercise interventions were performed 3.4 ± 1.4 days per week at moderate intensity (3.7 ± 0.6 metabolic equivalents) for 45.2 ± 17.0 minutes per session for 18.6 ± 10.0 weeks and consisted primarily of aerobic exercise (65%). Overall, there was a modest favorable effect of exercise on cognitive function (d+ = 0.47, 95% confidence interval (CI) = 0.26–0.68). Within‐group analyses revealed that exercise improved cognitive function (d+w = 0.20, 95% CI = 0.11–0.28), whereas cognitive function declined in the control group (d+w = −0.18, 95% CI = −0.36 to 0.00). Aerobic exercise had a moderate favorable effect on cognitive function (d+w = 0.65, 95% CI = 0.35–0.95), but other exercise types did not (d+w = 0.19, 95% CI = −0.06–0.43). Conclusion Our findings suggest that exercise training may delay the decline in cognitive function that occurs in individuals who are at risk of or have AD, with aerobic exercise possibly having the most favorable effect. Additional randomized controlled clinical trials that include objective measurements of cognitive function are needed to confirm our findings.

OBJECTIVE To investigate the effect of oral contraceptive (OC) use and compression socks on hemostatic activation in women flying cross-country to and from a marathon. DESIGN Prospective study. SETTING 2015 Boston Marathon. PARTICIPANTS Women were divided into non-OC using (CONTROL; n = 12), OC-using (OC; n = 15), and OC-using plus compression sock (OC + SOCK; n = 14) groups. INTERVENTION Women in OC + SOCK wore compression socks during flights to and from the marathon. MAIN OUTCOME MEASURES Venous blood samples were collected within 24 hours of arriving in Boston (EXPO), immediately after the marathon (RUN), and within 24 hours after a return flight home (Post-Flight) for analysis of thrombin-antithrombin complex (TAT), d-dimer, and tissue plasminogen activator (t-PA). RESULTS TAT did not increase with exercise (P = 0.48) and was not affected by group (P = 0.08) or the interaction between these 2 factors (P = 0.80). Group, time, and their interaction were significant for d-dimer (all P < 0.05) such that d-dimer increased with acute exercise to a greater extent (Δ d-dimer from expo to postrace = 909.5 ± 1021.9 ng/mL) in the OC + SOCK group relative to OC (Δ d-dimer = 240.0 ± 178.5 ng/mL; P = 0.02) and CONTROL (Δ d-dimer = 230.3 ± 120.3 ng/mL; P = 0.02). There was a significant effect of time, group, and the interaction on t-PA (all P < 0.01) such that t-PA increased with acute exercise to a greater extent (Δ t-PA from expo to postrace = 19.6 ± 10.0 ng/mL) in the CONTROL group relative to OC (Δ t-PA = 4.0 ± 1.8 ng/mL; P < 0.01) and OC + SOCK (Δ t-PA = 3.3 ± 1.2 ng/mL; P < 0.01). CONCLUSIONS Female runners using OCs did not exhibit disproportionately increased coagulation. The use of compression socks in women on OCs, surprisingly, resulted in a greater increase in d-dimer after exercise.

There are an increasing number of reports describing deep vein thrombosis (DVT) and/or pulmonary embolism (PE) in otherwise healthy endurance athletes. The Wells score is the most commonly used clinical prediction rule to diagnose DVT/PE in clinical populations. However, the Wells score may have limited utility for recognition of DVT/PE in athletes, contributing to missed or delayed diagnosis.We performed an analysis of the ability of the Wells score to identify DVT/PE events in athletes through a review of published case reports.A systematic search of the literature yielded 11 case reports.The Wells score had a 100% failure rate in identifying athletes with DVT (0/6) and PE (0/5), resulting in a delayed diagnosis for DVT of 20 ± 14 days. Retrospectively removing 'differential diagnosis' from the clinical prediction rule for DVT changed the Wells score median from 0 (range: -1 to 0) to 2 (range: 1 to 2); the threshold for predicting DVT as 'likely'. There were limited clinical characteristics captured in the Wells score for PE that were applicable to athletes, highlighting the need for reappraisal. Although the Wells score failed to accurately triage athletes with known DVT and/or PE, the addition of a D-dimer value (mean: 1566 ± 758ng/dL) to the Wells score correctly identified 9/9 athletes.The Wells score had a 100% failure rate for triaging athletes with known DVT/PE. When performed, D-dimer adequately facilitated the additional diagnostic testing required for a timely diagnosis of DVT/PE in athletes. Improving awareness of an atypical presentation of thrombotic events in athletes may reduce the widespread underestimation of DVT/PE among athletes and facilitate the additional testing required for a timely diagnosis.

The mechanisms underlying statin-associated muscle symptoms (SAMS) are not understood. Mitochondrial dysfunction and atrogin-1 activation are among the leading possible explanations for SAMS. Interestingly, metformin can enhance mitochondrial function and may affect atrogin-1 expression. Therefore, we sought to perform a systematic search of the literature to explore the relationship among statins, metformin, and SAMS.

Background 3-hydroxy-3-methylglutaryl coenzyme A reductase reductase inhibitors (statins) are generally well tolerated, with statin-associated muscle symptoms (SAMS) the most common side effect (~10%) seen in statin users. However, studies and clinical observations indicate that many of the self-reported SAMS appear to be nonspecific (ie, potentially not attributable to statins). Objective Mental health and well-being influence self-perception of pain, so we sought to assess the effect of baseline well-being and depression on the development of muscle pain with 6 months of atorvastatin 80 mg/d (ATORVA) or placebo in healthy, statin-naive adults. Methods The Psychological General Well-being Index (n = 83) and Beck Depression Inventory (n = 55) questionnaires were administered at baseline in participants (aged 59.5 ± 1.2 years) from the effect of Statins on Skeletal Muscle Function and Performance (STOMP) trial (NCT00609063). Muscle pain (Short-Form McGill Pain Questionnaire [SF-MPQ]), pain that interferes with daily life (Brief Pain Inventory [BPI]), and pain severity (BPI) were then measured before, throughout, and after treatment. Results At baseline, there were no differences in well-being (Psychological General Well-being Index), depression (Beck Depression Inventory), or pain measures (SF-MPQ and BPI) (P values ≥ .05) between the placebo and ATORVA groups. Baseline well-being correlated negatively with baseline BPI pain severity (r = -0.290, P = .008). Baseline depression correlated with baseline pain (SF-MPQ; r = 0.314, P = .020). Baseline well-being and depression did not predict the change in pain severity or interference after 6 months among the total sample or between groups (P values ≥ .05). Conclusion Baseline well-being and depression were not significant predictors of pain after 6 months of ATORVA (P values ≥ .05). Thus, they do not appear to increase the risk of SAMS in otherwise healthy adults.

FURIN is a proprotein convertase subtilisin/kexin enzyme important in pro‐renin receptor processing, and FURIN (furin, paired basic amino acid cleaving enzyme) variants are involved in multiple aspects of blood pressure (BP) regulation. Therefore, we examined associations among FURIN variants and the immediate blood pressure (BP) response to bouts of aerobic exercise, termed postexercise hypotension (PEH). Obese (30.9 ± 3.6 kg m−2) Black‐ (n = 14) and White‐ (n = 9) adults 42.0 ± 9.8 year with hypertension (139.8 ± 10.4/84.6 ± 6.2 mmHg) performed three random experiments: bouts of vigorous (VIGOROUS) and moderate (MODERATE) intensity cycling and control. Subjects were then attached to an ambulatory BP monitor for 19 h. We performed deep‐targeted exon sequencing with the Illumina TruSeq Custom Amplicon kit. FURIN genotypes were coded as the number of minor alleles (#MA) and selected for additional statistical analysis based upon Bonferonni or Benjamini–Yekutieli multiple testing corrected P‐values under time‐adjusted linear models for 19 hourly BP measurements. After VIGOROUS over 19 h, as FURIN #MA increased in rs12917264 (P = 2.4E‐04) and rs75493298 (P = 6.4E‐04), systolic BP (SBP) decreased 30.4–33.7 mmHg; and in rs12917264 (P = 1.6E‐03) and rs75493298 (P = 9.7E‐05), diastolic BP (DBP) decreased 17.6–20.3 mmHg among Blacks only. In addition, after MODERATE over 19 h in FURIN rs74037507 (P = 8.0E‐04), as #MA increased, SBP increased 20.8 mmHg among Blacks only. Whereas, after MODERATE over the awake hours in FURIN rs1573644 (P = 6.2E‐04), as #MA increased, DBP decreased 12.5 mmHg among Whites only. FURIN appears to exhibit intensity and race‐dependent associations with PEH that merit further exploration among a larger, ethnically diverse sample of adults with hypertension.

Introduction: HMG-CoA reductase inhibitors (statins) are generally well-tolerated, although muscle weakness and pain have been reported in ~10% of statin users. However, many self-reported muscle side effects are non-specific. As mental health influences self-perception of pain, we sought to assess the effect of baseline well-being and depression on self-reported muscle pain and quality of life (QOL) after 6 months of atorvastatin (ATORVA) 80 mg/d or placebo in healthy, statin-naïve adults. Hypothesis: We hypothesized that lower levels of well-being and higher levels of depression would result in higher self-reported pain that interferes with QOL after statin therapy. Methods: The Psychological General Well-Being Index (Well-Being; n=82) and Beck Depression Inventory (Depression; n=55) were administered at baseline in subjects (aged 59.5+1.2 yrs) from STOMP (Effect of Statins on Skeletal Muscle Performance; Clinical Trials #NCT00609063). Muscle pain (Short-Form McGill Pain Questionnaire [SF-MPG]) and pain that interferes with QOL (Brief Pain Inventory [BPI]), were also measured before and after drug treatment. Results: At baseline, there were no group differences in Well-Being, Depression, or pain measures between groups (ps ≥0.05). Baseline Well-Being correlated with baseline BPI pain severity (r=-0.309, p

Cardiovascular disease mortality is reduced following smoking cessation but the reversibility of specific atherogenic risk factors such as endothelial dysfunction is less established. We assessed brachial artery flow-mediated dilation (FMD) in 57 chronic smokers and 15 healthy controls, alone and after oral tetrahydrobiopterin (BH4) administration, to assess the extent to which reduced bioactivity of BH4, a cofactor for the endothelial nitric oxide synthase enzyme (eNOS), contributes to smoking-associated reductions in FMD. Thirty-four smokers then ceased cigarette and nicotine use for 1 week, after which FMD (±BH4 administration) was repeated. Brachial artery FMD was calculated as the peak dilatory response observed relative to baseline (%FMD). Endothelium-independent dilation was assessed by measuring the dilatory response to sublingual nitroglycerin (%NTG). Chronic smokers exhibited reduced %FMD relative to controls: (5.6±3.0% vs. 8.1±3.7%; P

Hydroxy-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors or statins are well tolerated, but associated with various statin-associated symptoms (SAS), including statin-associated muscle symptoms (SAMS), diabetes mellitus (DM), and central nervous system complaints. These are "statin-associated symptoms" because they are rare in clinical trials, making their causative relationship to statins unclear. SAS are, nevertheless, important because they prompt dose reduction or discontinuation of these life-saving mediations. SAMS is the most frequent SAS, and mild myalgia may affect 5% to 10% of statin users. Clinically important muscle symptoms, including rhabdomyolysis and statin-induced necrotizing autoimmune myopathy (SINAM), are rare. Antibodies against HMG-CoA reductase apparently provoke SINAM. Good evidence links statins to DM, but evidence linking statins to other SAS is largely anecdotal. Management of SAS requires making the possible diagnosis, altering or discontinuing the statin treatment, and using alternative lipid-lowering therapy.

Marathon running evokes parallel increases in markers of coagulation and fibrinolysis (i.e. hemostatic activation) immediately following strenuous, endurance exercise such that hemostatic balance is maintained. However, other factors incident to marathon running (i.e. dehydration, travel) may disproportionately activate the coagulatory system, increasing blood clot risk after an endurance event in otherwise healthy individuals. We investigated the effect of compression socks on exercise-induced hemostatic activation and balance in endurance athletes running the 2013 Hartford Marathon.Adults (n = 20) were divided into compression sock (SOCK; n = 10) and control (CONTROL; n = 10) groups. Age, anthropometrics, vital signs, training mileage and finishing time were collected. Venous blood samples were collected 1 day before, immediately after and 1 day following the marathon for analysis of coagulatory (i.e. thrombin-antithrombin complex [TAT] and D-dimer) and fibrinolytic (i.e. tissue plasminogen activator [t-PA]) factors.Plasma D-dimer, TAT and t-PA did not differ between groups at baseline (p0.16). There were no significant group · time interactions (all p ≥ 0.17), however, average t-PA was lower in SOCK (8.9 ± 0.7 ng/mL) than CONTROL (11.2 ± 0.7 ng/mL) (p = 0.04). Average TAT also tended to be lower in SOCK (2.8 ± 0.2 µg/L) than CONTROL (3.4 ± 0.2 µg/L) (p = 0.07).Our results suggest that overall hemostatic activation (both coagulation and fibrinolysis) following a marathon tended to be lower with compression socks. Thus, compression socks do not adversely influence markers of hemostasis, appear safe for overall use in runners and may reduce exercise-associated hemostatic activation in individuals at risk for deep vein thrombosis.

Purpose/methods. The Boston Athletic Association’s annual marathon, also referred to as BAA in this article, continues to be a source of subjects for exercise and endurance performance research. We performed a systematic literature review of BAA studies published in the 7 years since our prior report. Results. We identified 20 articles published from January 2008 to February 2015. Nine were related to cardiology; six were related to exercise physiology; four were related to metabolism; and one was related to marathon qualifying times. As in our prior, report cardiovascular studies remained the dominant topic, but with risk factors for atherosclerosis and thrombosis as the present focus. Conclusion. Cardiac issues remain the largest subject area for BAA studies, but with more emphasis on the effect of prolonged exercise on atherosclerotic and thrombotic risk factors. This shift is associated with an increase in marathon participation by older, recreational runners at increased risk of cardiac compl...

Dyslipidemia is a major risk factor for cardiovascular disease, with increasing numbers of adults being treated with cholesterol-lowering drugs (in particular, statin therapy) to treat elevated low-density lipoprotein cholesterol (LDL-C). Both aerobic exercise training and resistance training are efficacious for altering blood lipid levels, with evidence suggesting that aerobic exercise training raises high-density lipoprotein cholesterol (HDL-C) and lowers triglycerides, and resistance training may be more effective at lowering LDL-C. Consequently, concurrent aerobic and resistance training may be the most effective exercise prescription for improving dyslipidemia, although there is a paucity of randomized control trials addressing exercise dose-response for concurrent aerobic and resistance training and lipid-lipoprotein levels. In addition, exercise training may also potentiate the utility of cholesterol-lowering drugs, and there is limited evidence of interactions between exercise and pharmaceutical interventions that favorably impact hypertension and hyperlipidemia in the same individuals. This chapter summarizes evidence for and clinical considerations surrounding the role of exercise training in treating dyslipidemia.

Introduction. Vitamin D deficiency is associated with the onset and progression of hypertension and cardiovascular disease (CVD). However, mechanisms underlying vitamin D deficiency-mediated increased risk of CVD remain unknown. We sought to examine the differential effect of high-dose versus low-dose vitamin D supplementation on markers of arterial stiffness among ~40 vitamin D deficient adults with prehypertension.Methods. Participants were randomized to high-dose (4000 IU/d) versus low-dose (400 IU/d) oral vitamin D3 for 6 months. 24 hr ambulatory blood pressure (BP), carotid-femoral pulse wave velocity, and pulse wave analyses were obtained at baseline and after 6 months of vitamin D supplementation.Results. There were no changes in resting BP or pulse wave velocity over 6 mo regardless of vitamin D dose (allp>0.202). High-dose vitamin D decreased augmentation index and pressure by 12.3 ± 5.3% (p=0.047) and 4.0 ± 1.5 mmHg (p=0.02), respectively. However, these decreases in arterial stiffness were not associated with increases in serum 25-hydroxyvitamin D over 6 mo (p=0.425).Conclusion. High-dose vitamin D supplementation appears to lower surrogate measures of arterial stiffness but not indices of central pulse wave velocity.Clinical Trial Registration. This trial is registered with www.clinicaltrials.gov (Unique Identifier:NCT01240512).

In previous studies, we found an endothelial nitric oxide synthase gene ( NOS3 ) variant rs2070744 associated with the ambulatory blood pressure (BP) response following bouts of moderate and vigorous intensity acute exercise, termed post‐exercise hypotension (PEH). In a validation cohort, we sequenced NOS3 exons for associations with PEH. Obese (30.9 ± 3.6 kg . m −2 ) African American ( n = 14) [AF] and Caucasian ( n = 9) adults 42.0 ± 9.8 years with hypertension (139.8 ± 10.4/84.6 ± 6.2 mmHg) performed three random experiments: bouts of vigorous and moderate intensity cycling and control. Subjects were attached to an ambulatory BP monitor for 19 h. We performed deep‐targeted exon sequencing with the Illumina TruSeq Custom Amplicon kit. Variant genotypes were coded as number of minor alleles (#MA) and selected for additional statistical analysis based upon Bonferonni or Benjamini–Yekutieli multiple testing‐corrected P ‐values under time‐adjusted linear models for 19 hourly BP measurements for each subject. After vigorous intensity over 19 h, among NOS3 variants passing multiple testing thresholds, as the #MA increased in rs891512 ( P = 6.4E‐04), rs867225 ( P = 6.5E‐04), rs743507 ( P = 2.6E‐06), and rs41483644 ( P = 2.4E‐04), systolic (SBP) decreased from 17.5 to 33.7 mmHg; and in rs891512 ( P = 9.7E‐05), rs867225 ( P = 2.6E‐05), rs41483644 ( P = 1.6E‐03), rs3730009 ( P = 2.6E‐04), and rs77325852 ( P = 5.6E‐04), diastolic BP decreased from 11.1 mmHg to 20.3 mmHg among AF only. In contrast, after moderate intensity over 19 h in NOS3 rs3918164, as the #MA increased, SBP increased by 16.6 mmHg ( P = 2.4E‐04) among AF only. NOS3 variants exhibited associations with PEH after vigorous, but not moderate intensity exercise among AF only. NOS3 should be studied further for its effects on PEH in a large, ethnically diverse sample of adults with hypertension to confirm our findings.