Beth A. Taylor

Vitamin D Therapy in Individuals With Prehypertension or Hypertension The DAYLIGHT Trial

Background— A large body of epidemiological and experimental evidence suggests that vitamin D deficiency may promote hypertension. This raises the possibility that vitamin D supplementation could be a simple intervention to reduce blood pressure, but data from prospective, randomized trials are limited. Methods and Results— A double-blind, randomized, controlled trial was conducted at 4 sites in the United States. We enrolled 534 individuals 18 to 50 years of age with low vitamin D status (25-hydroxyvitamin D levels ⩽25 ng/mL) and systolic blood pressure of 120 to 159 mm Hg. Participants were randomized to high-dose (4000 IU/d) versus low-dose (400 IU/d) oral vitamin D3 for 6 months. The primary end point was change in mean 24-hour systolic blood pressure. Secondary end points included change in ambulatory diastolic blood pressure and clinic systolic and diastolic blood pressures. The median age was 38 years, and 62% of participants were men. Forty-six percent of participants were white, and 48% were black. The median 25-hydroxyvitamin D level at baseline was 15.3 ng/mL. Four-hundred fifty-five participants (85%) had at least 1 follow-up blood pressure measurement; 383 participants (72%) completed the full 6-month study. At the end of the study, there was no significant difference in the primary end point (change in mean 24-hour systolic blood pressure, −0.8 versus −1.6 mm Hg in the high-dose and low-dose arms; P=0.71) or in any of the secondary end points. Furthermore, there was no evidence of association between change in 25-hydroxyvitamin D and change in 24-hour systolic blood pressure at 6 months (Spearman correlation coefficient, −0.05, P=0.34). Results were consistent across prespecified subgroups. Conclusions— Vitamin D supplementation did not reduce blood pressure in individuals with prehypertension or stage I hypertension and vitamin D deficiency. Our findings suggest that the association between vitamin D status and elevated blood pressure noted in observational studies is not causal. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01240512.

An assessment by the Statin Cognitive Safety Task Force: 2014 update.

The National Lipid Associations Safety Task Force convened a consensus conference of experts to develop a position statement on cognitive function to revise and update that published originally by the Association in the 2006 assessment of statin safety by a panel of neurologists. The current expert panel was charged with addressing the specific issue of potential adverse cognitive effects attributable to statins. Search strategies recently used in systematic reviews were used to identify relevant evidence using keywords and topics via Medline searches from 1966 to December 2013. Manual searches of bibliographies were also conducted. Panel members were asked to use the evidence to formulate answers to a series of questions of relevance to the subject matter. The strength of recommendations and quality of evidence were graded using accepted contemporary definitions and procedures. Recommendations to patients, health professionals, and researchers were put forth by the panel to aid in daily clinical decision making, and in future research endeavors.

Influence of chronic exercise on carotid atherosclerosis in marathon runners

Objectives The effect of habitual, high-intensity exercise training on the progression of atherosclerosis is unclear. We assessed indices of vascular health (central systolic blood pressure (SBP) and arterial stiffness as well as carotid intima-medial thickness (cIMT)) in addition to cardiovascular risk factors of trained runners versus their untrained spouses or partners to evaluate the impact of exercise on the development of carotid atherosclerosis. Setting field study at Boston Marathon. Participants 42 qualifiers (mean age±SD: 46±13 years, 21 women) for the 2012 Boston Marathon and their sedentary domestic controls (46±12 years, n=21 women). Outcomes We measured medical and running history, vital signs, anthropometrics, blood lipids, C reactive protein (CRP), 10 years Framingham risk, central arterial stiffness and SBP and cIMT. Results Multiple cardiovascular risk factors, including CRP, non-high-density lipoprotein cholesterol, triglycerides, heart rate, body weight and body mass index (all p<0.05), were reduced in the runners. The left and right cIMT, as well as central SBP, were not different between the two groups (all p>0.31) and were associated with age (all r≥0.41; p<0.01) and Framingham risk score (all r≥0.44; p<0.01) independent of exercise group (all p>0.08 for interactions). The amplification of the central pressure waveform (augmentation pressure at heart rate 75 bpm) was also not different between the two groups (p=0.07) but was related to age (p<0.01) and group (p=0.02) in a multiple linear regression model. Conclusions Habitual endurance exercise improves the cardiovascular risk profile, but does not reduce the magnitude of carotid atherosclerosis associated with age and cardiovascular risk factors.

Muscle-related side-effects of statins: from mechanisms to evidence-based solutions.

Purpose of review This article highlights the recent findings regarding statin-associated muscle side effects, including mechanisms and treatment as well as the need for more comprehensive clinical trials in statin myalgia. Recent findings Statin myalgia is difficult to diagnose and treat, as major clinical trials have not routinely assessed muscle sideeffects, there are few clinically relevant biomarkers and assessment tools for the symptoms, many apparent statin-related muscle symptoms may be nonspecific and related to other drugs or health conditions, and prevalence estimates vary widely. Data thus suggest that only 30–50% of patients with self-reported statin myalgia actually experience muscle pain on statins during blinded, placebo-controlled trials. In addition, evidence to date involving mechanisms underlying statin myalgia and its range of symptoms and presentations supports the hypothesis that there are multiple, interactive and potentially additive mechanisms underlying statin-associated muscle side-effects. Summary There are likely multiple and interactive mechanisms underlying statin myalgia, and recent studies have produced equivocal data regarding prevalence of statin-associated muscle side-effects, contributing factors and effectiveness of common interventions. Therefore, more clinical trials on statin myalgia are critical to the field, as are systematic resources for quantifying, predicting and reporting statin-associated muscle side-effects.

The Statin-Associated Muscle Symptom Clinical Index (SAMS-CI): Revision for Clinical Use, Content Validation, and Inter-rater Reliability

PurposeThe Statin-Associated Muscle Symptom Clinical Index (SAMS-CI) is a method for assessing the likelihood that a patient’s muscle symptoms (e.g., myalgia or myopathy) were caused or worsened by statin use. The objectives of this study were to prepare the SAMS-CI for clinical use, estimate its inter-rater reliability, and collect feedback from physicians on its practical application.MethodsFor content validity, we conducted structured in-depth interviews with its original authors as well as with a panel of independent physicians. Estimation of inter-rater reliability involved an analysis of 30 written clinical cases which were scored by a sample of physicians. A separate group of physicians provided feedback on the clinical use of the SAMS-CI and its potential utility in practice.ResultsQualitative interviews with providers supported the content validity of the SAMS-CI. Feedback on the clinical use of the SAMS-CI included several perceived benefits (such as brevity, clear wording, and simple scoring process) and some possible concerns (workflow issues and applicability in primary care). The inter-rater reliability of the SAMS-CI was estimated to be 0.77 (confidence interval 0.66–0.85), indicating high concordance between raters. With additional provider feedback, a revised SAMS-CI instrument was created suitable for further testing, both in the clinical setting and in prospective validation studies.ConclusionsWith standardized questions, vetted language, easily interpreted scores, and demonstrated reliability, the SAMS aims to estimate the likelihood that a patient’s muscle symptoms were attributable to statins. The SAMS-CI may support better detection of statin-associated muscle symptoms in clinical practice, optimize treatment for patients experiencing muscle symptoms, and provide a useful tool for further clinical research.

Influence of statins on distinct circulating microRNAs during prolonged aerobic exercise.

Statins exacerbate exercise-induced skeletal muscle injury. Muscle-specific microRNAs (myomiRs) increase in plasma after prolonged exercise, but the patterns of myomiRs release after statin-associated muscle injury have not been examined. We examined the relationships between statin exposure, in vitro and in vivo muscle contraction, and expression of candidate circulating myomiRs. We measured plasma levels of myomiRs, circulating microRNA-1 (c-miR-1), c-miR-133a, c-miR-206, and c-miR-499-5p from 28 statin-using and 28 nonstatin-using runners before (PRE), immediately after (FINISH), and 24 h after they ran a 42-km footrace (the 2011 Boston marathon) (POST-24). To examine these cellular-regulation myomiRs, we used contracting mouse C2C12 myotubes in culture with and without statin exposure to compare intracellular and extracellular expression of these molecules. In marathoners, c-miR-1, c-miR-133a, and c-miR-206 increased at FINISH, returned to baseline at POST-24, and were unaffected by statin use. In contrast, c-miR-499-5p was unchanged at FINISH but increased at POST-24 among statin users compared with PRE and runners who did not take statins. In cultured C2C12 myotubes, extracellular c-miR-1, c-miR-133a, and c-miR-206 were significantly increased by muscle contraction regardless of statin use. In contrast, extracellular miR-499-5p was unaffected by either isolated statin exposure or isolated carbachol exposure but it was increased when muscle contraction was combined with statin exposure. In summary, we found that statin-potentiated muscle injury during exercise is accompanied by augmented extracellular release of miR-499-5p. Thus c-miR-499-5p may serve as a biomarker of statin-potentiated muscle damage.

Changes in Muscle Strength in Patients With Statin Myalgia

Statins can produce myalgia or muscle pain, which may affect medication adherence. We measured the effects of statins on muscle strength in patients with previous statin myalgia. Leg isokinetic extension average power at 60° per second (-8.8 ± 10.5N-M, p = 0.02) and average peak torque at 60° per second (-14.0 ± 19.7N-M, p = 0.04) decreased slightly with statin use, but 8 of 10 other variables for leg strength did not change (all p >0.13). Handgrip, muscle pain, respiratory exchange ratio, and daily activity also did not change (all p >0.09). In conclusion, statin myalgia is not associated with reduced muscle strength or muscle performance.

Can Exercise Improve Cognitive Symptoms of Alzheimer's Disease?

To examine the effects of exercise training on cognitive function in individuals at risk of or diagnosed with Alzheimers disease (AD).

Coming of Age: Considerations in the Prescription of Exercise for Older Adults.

Older adults represent the fastest-growing age demographic of the population. Physiological changes associated with primary aging and concurrent chronic disease adversely impact functional capacity, health outcomes, and quality of life. For these reasons, there is a national emphasis for healthcare providers to improve the health, function, and quality of life of older adults to preserve independent living and psychological well-being. The benefits of regular physical activity or exercise with regard to aging and disease are indisputable, yet many clinicians do not prescribe exercise to older adults. This reluctance may be attributable to a lack of knowledge regarding appropriate exercise prescription for older adults in light of the potential risks and benefits of various doses and types of exercise. In addition, clinicians and patients may have concerns about potential health considerations relevant to older adults such as comprehensive pre-exercise screening and exercise-drug interactions. In light of this, the following review presents (1) guidelines for exercise prescription in older adults and modification of these guidelines for patients with the most common age-associated comorbidities; (2) recommendations for pre-exercise screening prior to initiating an exercise program in older adults; (3) considerations for older adults on one or more medications; and (4) common barriers to adopting and maintaining exercise in an older population. Our goal is to provide a framework that clinicians can follow when prescribing exercise in older adults while considering the unique characteristics and concerns present in this population.

The Effect of Atorvastatin on Habitual Physical Activity among Healthy Adults

PURPOSE Statin therapy can result in muscle pain, cramps, and weakness that may limit physical activity, although reports are mixed. We conducted a randomized control trial to examine the effect of atorvastatin on habitual physical activity levels in a large sample of healthy adults. METHODS Participants (n = 418) were statin-naive adults (44.0 ± 16.1 yr (mean ± SD)) who were randomized and double-blinded to 80 mg · d(-1) of atorvastatin or placebo for 6 months. Accelerometers were worn for 96 h before and after drug treatment. Repeated-measures analysis tested physical activity levels after versus those before drug treatment among groups with age and VO2max as covariates. RESULTS In the total sample, sedentary behavior increased (19.5 ± 5.1 min · d(-1)), whereas light-intensity (9.1 ± 3.0 min · d(-1)) and moderate-intensity (9.7 ± 2.8 min · d(-1)) physical activity decreased, as did total activity counts (17.8 ± 6.3 d × 10(-3)) over 6 months (P < 0.01), with no differences between groups. The atorvastatin group increased sedentary behavior (19.8 ± 7.4 min · d(-1)) and decreased light-intensity (10.7 ± 4.3 min · d(-1)) and moderate-intensity (8.5 ± 4.0 min · d(-1)) physical activity (P < 0.05). On the other hand, the placebo group increased sedentary behavior (19.2 ± 7.1 min · d(-1)) and decreased moderate-intensity (11.0 ± 3.8 min · d(-1)) and total physical activity counts (-23.8 ± 8.8 × 10(-3) d(-1)) (P < 0.05). CONCLUSIONS Time being sedentary increased and physical activity levels decreased in the total sample over 6 months of drug treatment, independent of group assignment. Our results suggest that statins do not influence physical activity levels any differently from placebo, and the lack of inclusion of a placebo condition may provide insight into inconsistencies in the literature.