Erin D Michos

Elevated parathyroid hormone (PTH) levels have been associated with cardiovascular disease risk factors and events. We hypothesized that elevated PTH levels would also be associated with subclinical cerebrovascular disease. We examined the relationship between elevated PTH level and white matter hyperintensities (WMHs) and subclinical infarcts measured on brain magnetic resonance imaging (MRI). PTH was measured at baseline (1993-1994) among participants free of prior clinical stroke who underwent a brain MRI at baseline (n = 1703) and a second brain MRI 10 years later (n = 948). PTH levels of 65 pg/mL or higher were considered elevated (n = 204). Participants who did not return for a follow-up MRI had, at baseline, higher PTH and a greater prevalence of cardiovascular risk factors (P < .05 for all); therefore, multiple imputation was used. The cross-sectional and prospective associations of PTH levels with WMH and MRI-defined infarcts (and their progression) were investigated using multivariable regression models. At baseline, the participants had a mean age of 62 years and were 60% female and 49% black. Cross-sectionally, after adjusting for demographic and lifestyle factors, elevated PTH level was associated with higher WMH score (β = .19, 95% confidence interval [CI] .04-.35) and increased odds of prevalent infarcts (odds ratio 1.56, 95% CI 1.02-2.36). Results were attenuated after adjustment for potential mediators of this association (i.e., hypertension). No prospective associations were found between PTH and incident infarcts or change in estimated WMH volume, although estimates were imprecise. Although associated cross-sectionally, we did not confirm any association between elevated PTH level and progression of cerebrovascular changes on brain MRIs obtained 10 years apart. The relationship of PTH with subclinical brain disease warrants further study.

We hypothesized that a fully automated mobile health (mHealth) intervention with tracking and texting components would increase physical activity. mActive enrolled smartphone users aged 18 to 69 years at an ambulatory cardiology center in Baltimore, Maryland. We used sequential randomization to evaluate the intervention's 2 core components. After establishing baseline activity during a blinded run-in (week 1), in phase I (weeks 2 to 3), we randomized 2:1 to unblinded versus blinded tracking. Unblinding allowed continuous access to activity data through a smartphone interface. In phase II (weeks 4 to 5), we randomized unblinded participants 1:1 to smart texts versus no texts. Smart texts provided smartphone-delivered coaching 3 times/day aimed at individual encouragement and fostering feedback loops by a fully automated, physician-written, theory-based algorithm using real-time activity data and 16 personal factors with a 10 000 steps/day goal. Forty-eight outpatients (46% women,...

A single measurement of 25-hydroxyvitamin D [25(OH)D] may not accurately reflect long-term vitamin D status. Little is known about change in 25(OH)D levels over time, particularly among blacks. To determine longitudinal changes in 25(OH)D levels among Atherosclerosis Risk in Communities (ARIC) study participants. Longitudinal study. General community. 9890 white and 3222 black participants at visit 2 (1990-1992), 888 whites and 876 blacks at visit 3 (1993-1994), and 472 blacks at the brain visit (2004-2006). 25(OH)D levels were measured, and regression models were used to assess associations between clinical factors and longitudinal changes in 25(OH)D. Vitamin D deficiency [<50 nmol/L (<20 ng/ml)] was seen in 23% and 25% of whites at visits 2 and 3, and in 61%, 70%, and 47% of blacks at visits 2, 3, and the brain visit, respectively. 25(OH)D levels were correlated between visits 2 and 3 (3-year interval) among whites (r=0.73) and blacks (r=0.66). Among blacks, the correlation ...

Cardiovascular disease is the leading cause of death among women in the U.S., exceeding breast cancer mortality in women of all ages. Women present with cardiovascular disease a decade after men, and this has been attributed to the protective effect of female ovarian sex hormones that is lost after menopause. Animal and observational studies have shown beneficial effects of hormone therapy when it is initiated early in the perimenopausal period or before the development of significant atherosclerosis. However, randomized, placebo-controlled trials in older women have not shown any benefit in either primary prevention or secondary prevention of cardiovascular events, with a concerning trend toward harm. This review outlines the lessons learned from the basic science, animal, observational, and randomized trials, and then summarizes yet-unanswered questions of hormone therapy and cardiovascular risk.

It is unclear whether antihypertensive treatment can restore cardiovascular disease risk to the risk level of persons with ideal blood pressure (BP) levels. Data from the Multi-Ethnic Study of Atherosclerosis (MESA) and the Coronary Artery Risk Development in Young Adults (CARDIA) study were analyzed. Outcomes were compared among participants without or with antihypertensive treatment at 3 BP levels: <120/<80 mm Hg, systolic BP 120 to 139 mm Hg or diastolic BP 80 to 89 mm Hg (120 to 129/≤80 mm Hg for participants with diabetes), and systolic BP ≥140 or diastolic BP ≥90 mm Hg (systolic BP ≥130 or diastolic BP ≥80 mm Hg for participants with diabetes). Among MESA participants aged ≥50 years at baseline, those with BP <120/<80 mm Hg on treatment had higher left ventricular mass index, prevalence of estimated glomerular filtration rate <60 mL/min per 1.73 m(2), prevalence of coronary calcium score >100, and twice the incident cardiovascular disease rate over 9.5 years of follow-up than those with BP <120/<80 mm Hg without treatment. In CARDIA at year 25, persons with BP <120/<80 mm Hg with treatment had much longer exposure to higher BP and higher risk of end-organ damage and subclinical atherosclerosis than those with BP <120/<80 mm Hg without treatment. An exploratory analysis suggested that when cumulative systolic BP was high (eg, >3000 mm Hg-years in 25 years), the increase in left ventricular mass index accelerated. The data suggest that based on the current approach, antihypertensive treatment cannot restore cardiovascular disease risk to ideal levels. Emphasis should be placed on primordial prevention of BP increases to further reduce cardiovascular disease morbidity and mortality.

The impact of replacing the National Cholesterol Education Program (NCEP)/Adult Treatment Program (ATP) III cholesterol guidelines with the new 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for primary prevention of cardiovascular disease is unclear. We used risk factor and 10-year clinical event rate data from MESA, combined with estimates of efficacy of moderate and high-intensity statin therapy from meta-analyses of statin primary prevention trials to estimate (a) the change in number of subjects eligible for drug therapy and (2) the anticipated reduction in atherosclerotic cardiovascular disease (ASCVD) events and increment in type 2 diabetes mellitus (T2DM) associated with the change in cholesterol guidelines. Of the 6,814 MESA participants, 5,437 were not on statins at baseline and had complete data for analysis (mean age 61.4±10.3). Using the NCEP/ATP III guidelines, 1,334 (24.5%) would have been eligible for statin therapy compared wit...

Given that sympathetic tone is associated with hypertension, we sought to determine whether resting heart rate (RHR), as a surrogate for cardiac autonomic function, was associated with incident hypertension. We analyzed 21,873 individuals without a history of hypertension who underwent a clinically indicated exercise stress test. Baseline RHR was assessed prior to testing and was categorized as <70, 70-85, and >85 beats-per-minute (bpm). Incident hypertension was defined by subsequent diagnosis codes for new-onset hypertension from three or more encounters. We tested for effect modification by age (<60 vs. ≥60 years), sex, race, and history of coronary heart disease (CHD). Mean (±SD) age was 49 (±12) years, 55% were men and 21% were Black. Compared to the lowest RHR (<70 bpm) category, patients in the highest category (>85 bpm) were younger, more likely to be female, heavier, diabetic, and achieve lower metabolic equivalents (METS). Over a median of 4 years follow-up,...

Smoking-related microvascular loss causes end-organ damage in the kidneys, heart and brain. Basic research suggests a similar process in the lungs but no large studies have assessed pulmonary microvascular blood flow (PMBF) in early chronic lung disease. We hypothesized that PMBF is reduced in mild as well as more severe COPD and emphysema. PMBF was measured using gadolinium-enhanced magnetic resonance imaging (MRI) among smokers with COPD and controls age 50-79 years without clinical cardiovascular disease. COPD severity was defined by standard criteria. Emphysema on computed tomography (CT) was defined by percent of lung regions <-950 Hounsfield units and radiologists using a standard protocol. We adjusted for potential confounders including smoking, oxygenation and left ventricular cardiac output. Among 144 participants, PMBF was reduced by 30% in mild COPD, 29% in moderate COPD and 52% in severe COPD (all P<0.01 vs. controls). PMBF was reduced with greater percent emphysem...

In observational studies, low 25-hydroxyvitamin D (25(OH)D) has been associated with increased risk of coronary heart disease (CHD), and this association may vary by race. Racial differences in the frequency of vitamin D binding protein (DBP) single nucleotide polymorphisms (SNPs) might account for similar bioavailable vitamin D in blacks despite lower mean 25(OH)D. We hypothesized that the associations of low 25(OH)D with CHD risk would be stronger among whites and among persons with genotypes associated with higher DBP levels. We measured 25(OH)D by mass spectroscopy in 11,945 participants in the ARIC Study (baseline 1990-1992, mean age 57 years, 59% women, 24% black). Two DBP SNPs (rs7041; rs4588) were genotyped. We used adjusted Cox proportional hazards models to examine the association of 25(OH)D with adjudicated CHD events through December 2011. Over a median of 20 years, there were 1230 incident CHD events. Whites in the lowest quintile of 25(OH)D (<17 ng/ml) compared to t...

Diabetics are at high risk for atherosclerotic cardiovascular disease (ASCVD) and are considered a coronary heart disease risk equivalent. The utility of aspirin in primary prevention of ASCVD in diabetic patients has been widely studied and is still debated. Overall, the current evidence suggests a modest benefit for reduction in ASCVD events with the greatest benefit among those with higher baseline risk, but at the cost of increased risk of gastrointestinal bleeding. Diabetic patients at higher risk (with 10-year ASCVD risk >10 %) are generally recommended for aspirin therapy if bleeding risk is felt to be low. A patient-provider discussion is recommended before prescribing aspirin therapy. Novel markers such as coronary artery calcium scores and high-sensitivity C-reactive protein may help refine ASCVD risk prediction and guide utility for aspirin therapy. This article will review the literature for the most up-to-date studies evaluating aspirin therapy for primary prevention...

Vitamin D and calcium have traditionally been viewed in relation to bone health. However, recent research has suggested relations between these nutrients and cardiovascular disease (CVD). Specifically, evidence from both observational studies and clinical trials suggests that vitamin D may be related to lower risk of CVD. The picture for calcium is more complex. Dietary intake of calcium may be associated with lower CVD risk, while calcium supplementation may elevate CVD risk. In this review, we summarize evidence of these relations, and comment on the recent Institute of Medicine (IOM) recommendations regarding use of vitamin D and calcium supplements.

Vitamin D is widely known for its important role in bone health. More recent evidence suggests that vitamin D may also play a protective role in many chronic conditions, including cancer, autoimmune, kidney, and cardiovascular diseases (CVDs). Observational studies have associated low vitamin D levels with CVD risk factors, including hypertension, hyperlipidemia, diabetes, and metabolic syndrome, as well as with

Women have less risk of atherosclerotic cardiovascular disease compared with men up until midlife (ages 50 to 60), after which the gap begins to narrow post menopause. We hypothesized that the average lipid profile of women undergoes unfavorable changes compared with men after midlife. We examined lipids by sex and age in the Very Large Database of Lipids 10B (VLDL 10B) study. The analysis included 1 350 908 unique consecutive patients clinically referred for lipoprotein testing by density gradient ultracentrifugation from 2009 to 2011. Ratio variables were created for density subclasses of LDL-C, HDL-C, and VLDL-C (LLDR, LHDR, LVDR, respectively). Men showed higher median LDL-C values than women for ages 20 to 59, with the greatest difference in their 30s: 146 mg/dL in men versus 130 mg/dL in women. In contrast, women consistently had higher values after midlife (age 60), for example ages 70 to 79: 129 mg/dL in women versus 112 mg/dL in men. After age 50, women had higher LDL-C eac...

Clinicians face uncertainty about the prognostic value of troponin testing in patients with chronic kidney disease (CKD) without suspected acute coronary syndrome (ACS). To systematically review the literature on troponin testing in patients with CKD without ACS. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through May 2014. Studies examining elevated versus normal troponin levels in patients with CKD without ACS. Paired reviewers selected articles for inclusion, extracted data, and graded strength of evidence (SOE). Meta-analyses were conducted when studies had sufficient homogeneity of key variables. Ninety-eight studies met inclusion criteria. Elevated troponin levels were associated with all-cause and cardiovascular mortality among patients receiving dialysis (moderate SOE). Pooled hazard ratios (HRs) for all-cause mortality from studies that adjusted for age and coronary artery disease or a risk equivalent were 3.0 (95% CI, 2.4 to 4.3) for troponin T ...

A number of metabolic syndrome (MS) definitions exist, and one's cardiovascular disease risk may depend on the definition used. The authors compared the association of subclinical atherosclerosis (coronary artery calcification [CAC] score >0] and inflammation (white blood cell [WBC] count greater than or equal to the highest quartile) with 3 definitions of MS (those of the National Cholesterol Education Program Adult Treatment Panel III [NCEP ATP III], the American Heart Association/National Heart, Lung and Blood Institute [AHA/NHLBI], and the International Diabetes Federation [IDF]) in 458 asymptomatic men (mean age, 46+/-7 years). MS was present in 28%, 29%, and 34% according to NCEP ATP III, AHA/NHLBI, and IDF criteria, respectively. CAC was observed in 40% and high WBC count in 24%. After adjustment for age, smoking, and low-density lipoprotein cholesterol, the odds ratios for CAC scores >0 with MS by NCEP ATP III, AHA/NHLBI, and IDF definitions were 1.67 (95% confidence interval [CI], 1.02-2.72), 1.67 (95% CI, 1.03-2.70), and 1.63 (95% CI, 1.03-2.57), respectively. The multivariate odds ratios for high WBC count with MS by NCEP ATP III, AHA/NHLBI, and IDF definitions were 1.69 (95% CI, 1.04-2.73), 1.84 (95% CI, 1.14-2.95), and 1.66 (95% CI, 1.05-2.62), respectively. MS is associated with increased subclinical atherosclerosis and inflammation irrespective of various definitions.

Whether resting heart rate (RHR) predicts mortality independent of fitness is not well established, particularly among women. We analyzed data from 56,634 subjects (49% women) without known coronary artery disease or atrial fibrillation who underwent a clinically indicated exercise stress test. Baseline RHR was divided into 5 groups with <60 beats/min as reference. The Social Security Death Index was used to ascertain vital status. Cox hazard models were performed to determine the association of RHR with all-cause mortality, major adverse cardiovascular events, myocardial infarction, or revascularization after sequential adjustment for demographics, cardiovascular disease risk factors, medications, and fitness (metabolic equivalents). The mean age was 53 ± 12 years and mean RHR was 73 ± 12 beats/min. More than half of the participants were referred for chest pain; 81% completed an adequate stress test and mean metabolic equivalents achieved was 9.2 ± 3. There were 6,255 deaths ov...

Coronary artery calcium (CAC), carotid intima-media thickness (CIMT), and reduced ankle brachial indices (ABI) are markers of subclinical vascular disease strongly associated with aging. The authors identified factors associated with low levels of subclinical vascular disease in 1824 participants 70 years and older in the Multi-Ethnic Study of Atherosclerosis. A total of 452 had low CAC (<25th percentile), 441 had low CIMT (<25th percentile), 1636 had normal ABI (>0.9), and 165 had a combination index indicating favorable values for all 3 parameters. This combination index was independently associated with younger age (odds ratio [OR] 2.5 per 1 SD [95% confidence interval (CI), 1.8-3.6]), female sex (OR 3.0 [95% CI, 1.9-4.8]), lower body mass index (OR 1.6 per 1 SD [95% CI, 1.2-2.0]), absence of hypertension (OR 1.8 [95% CI, 1.2-2.6]), absence of dyslipidemia (OR 1.6 [95% CI, 1.04-2.4]), and never-smoking (OR 1.7 [95% CI, 1.1-2.6]). No significant associations were observed for C-reactive protein, education, diet, or physical activity. Favorable levels of multiple traditional risk factors, but not several novel risk factors, were associated with subclinical markers of successful cardiovascular aging.

Evidence on the association of vitamin D with cardiovascular risk factors in youth is very limited. We examined whether low serum vitamin D levels (25-hydroxyvitamin D [25(OH)D]) are associated with cardiovascular risk factors in US adolescents aged 12 to 19 years. We conducted a cross-sectional analysis of 3577 fasting, nonpregnant adolescents without diagnosed diabetes who participated in the 2001-2004 National Health and Nutrition Examination Survey. Cardiovascular risk factors were measured using standard methods and defined according to age-modified Adult Treatment Panel III definitions. Mean 25(OH)D was 24.8 ng/mL; it was lowest in black (15.5 ng/mL), intermediate in Mexican American (21.5 ng/mL), and highest in white (28.0 ng/mL) adolescents (P < .001 for each pairwise comparison). Low 25(OH)D levels were strongly associated with overweight status and abdominal obesity (P for trend < .001 for both). After adjustment for age, gender, race/ethnicity, BMI, socioeconomic status, and physical activity, 25(OH)D levels were inversely associated with systolic blood pressure (P = .02) and plasma glucose concentrations (P = .01). The adjusted odds ratio (95% confidence interval) for those in the lowest (<15 ng/mL) compared with the highest quartile (>26 ng/mL) of 25(OH)D for hypertension was 2.36 (1.33-4.19); for fasting hyperglycemia it was 2.54 (1.01-6.40); for low high-density lipoprotein cholesterol it was 1.54 (0.99-2.39); for hypertriglyceridemia it was 1.00 (0.49-2.04); and for metabolic syndrome it was 3.88 (1.57-9.58). Low serum vitamin D in US adolescents is strongly associated with hypertension, hyperglycemia, and metabolic syndrome, independent of adiposity.

Sex hormones are thought to play an important role in the pathophysiology of depressive disorders in women. This study assessed the associations of total testosterone (T), bioavailable T, estradiol, dehydroepiandrosterone, and sex hormone-binding globulin (SHBG) with depressive symptoms stratified on postmenopausal stage to determine whether the associations were strongest for early postmenopausal women. Women (N = 1,824) free of depressive symptoms at baseline (2000-2002) in the Multiethnic Study of Atherosclerosis were categorized into tertiles of years postmenopause: T1, 0 to 10 years; T2, 11 to 20 years; and T3, 21 to 58 years. Multivariable-adjusted relative risks (RRs) and 95% CIs were computed for the incidence of depressive symptoms, as defined by a score of 16 or higher on the Center for Epidemiologic Studies Depression scale at examination 3 (2004-2005). In analysis including all sex hormones, the RR for incident depressive symptoms associated with 1 unit higher log total T was 0.57 (P = 0.13), with log estradiol was 0.78 (P = 0.04), with log SHBG was 1.84 (P = 0.003), and with log dehydroepiandrosterone was 1.45 (P = 0.08) in T1. Without adjustment for SHBG, the RR for log bioavailable T was 0.16 (P = 0.04). However, in T2 and T3, there were no meaningful associations of hormone or SHBG levels with incident depressive symptoms. When stratified by HT use, results were consistent for HT users but attenuated for HT nonusers. In early postmenopausal women, sex hormones were associated with incident depressive symptoms.

Three levels of risk (low, intermediate, and high) are identified. The 2001 NCEP ATP-III guidelines define intermediate risk as a 10% to 20% risk of a nonfatal myocardial infarction or CHD death over the next 10 years, whereas the 2003 American College of Cardiology Bethesda ...

Evaluation of: Knekt P, Laaksonen M, Mattila C et al.: Serum vitamin D and subsequent occurrence of Type 2 diabetes. Epidemiology 19, 666-671 (2008). Cross-sectional studies have demonstrated that lower serum 25-hydroxyvitamin D (25[OH]D) levels are associated with obesity, the metabolic syndrome, impaired glucose tolerance and diabetes. However, as in all cross-sectional studies, the direction of causation is unclear. The article by Knekt et al. was the first prospective study to demonstrate that low 25(OH)D levels predict incident diabetes. This study utilized a nested case-control design of 412 incident diabetes cases and 986 age/sex matched controls drawn from two large Finnish cohorts totaling 7503 participants aged 40 years and over followed for up to 22 years. In men, although not in women, higher baseline 25(OH)D reduced the risk of incident diabetes by 72%. Recently, other prospective cohort studies have shown that baseline 25(OH)D deficiency is associated with incident cardiovascular disease events and mortality over follow-up, a relationship that may be mediated, in part, through incident diabetes. While animal studies and smaller interventional trials in humans suggest that vitamin D supplementation improves measures of insulin sensitivity and glucose tolerance, larger interventional trials are warranted to determine if vitamin D treatment at adequate doses can prevent diabetes.

Vitamin D deficiency has been linked to an increased risk of hypertension, diabetes, congestive heart failure, peripheral arterial disease, myocardial infarction, stroke, and related mortality, even after adjustment for traditional cardiovascular risk factors. Accumulating evidence from experimental, clinical, and epidemiological studies suggests that vitamin D may also be associated with several indices of vascular function, including the development and progression of atherosclerotic cardiovascular disease. These findings may provide at least a partial explanation for several recent epidemiologic studies implicating low vitamin D status in the pathogenesis of cardiovascular disease. However, many questions still remain. Only a handful of studies are currently available, and the results of these studies have generally been mixed. Additionally, it is unknown whether findings differ across varied subpopulations, including minority subgroups in the United States, younger adults, and those residing in areas with varying amounts of regular sunlight. Furthermore, the exact mechanism by which vitamin D may influence the atherosclerotic disease process has not yet been completely elucidated. In addition, if vitamin D is important in the etiology of atherosclerosis, it is unclear at what stage(s) in the atherosclerotic disease process vitamin D may exert its effects. Large-scale, well-conducted, placebo controlled clinical trials testing the efficacy of vitamin D supplementation in delaying, slowing, or reverting the atherosclerotic disease process have not yet been conducted. Until the results of these studies are available, we believe it is premature to recommend vitamin D as a therapeutic option in atherosclerosis.

ABSTRACT Background: Patients with chronic kidney disease (CKD) not requiring dialysis have a high prevalence of 25-hydroxyvitamin D (25(OH)D) deficiency but the relationship between 25(OH)D levels and metabolic syndrome is unknown in this population. Methods: This study analyzed stored plasma samples from 495 non-diabetic subjects with severe kidney disease, not yet on dialysis, who participated in the homocysteine in kidney and end stage renal disease study. Metabolic syndrome was defined as the presence of all three of the following: (1) Serum triglycerides ≥ 150 mg/dl or drug treatment for hypertriglyceridemia; (2) serum high density lipoprotein-cholesterol (HDL-C) < 50 mg/dl for women or < 40 mg/dl for men or drug treatment for dyslipidemia; and (3) blood pressure ≥ 130/85 mmHg or drug treatment for hypertension. Multivariate logistic regression models were used to evaluate the cross-sectional association between plasma 25(OH)D levels and metabolic syndrome. Results: The prevalence of metabolic syndrome increased as 25(OH)D levels declined, with the highest prevalence in participants with 25(OH)D levels < 20 ng/ml. Participants with 25(OH)D levels < 20 ng/ml had a significantly increased risk of metabolic syndrome compared to subjects with levels > 30 ng/ml after adjustment for multiple confounders (OR 2.25, 95% CI 1.25 - 4.07). Plasma 25(OH)D levels were inversely associated with diastolic blood pressure (R = -0.10, p = 0.029) and serum triglyceride levels (R = -0.14, p = 0.002). Conclusion: 25(OH)D deficiency is strongly associated with an increased risk of metabolic syndrome in non-diabetic patients with severe CKD not yet on dialysis, independent of cardiometabolic risk factors and other important regulators of mineral metabolism.