Jared P. Reis

Vitamin D Status and Cardiometabolic Risk Factors in the United States Adolescent Population

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: Low serum vitamin D in US adolescents is strongly associated with hypertension, hyperglycemia, and metabolic syndrome, independent of adiposity.

Relation of 25-hydroxyvitamin D and parathyroid hormone levels with metabolic syndrome among US adults

OBJECTIVE Previous research on the combined association of 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone (PTH) with metabolic syndrome may have been limited by restricted age variability and a lack of representation of the general population. This study examined the combined association of 25(OH)D and PTH with Adult Treatment Panel III-defined MetSyn among a nationally representative sample of US adults. DESIGN AND METHODS This population-based cross-sectional study included 834 men and 820 women aged > or =20 years without diagnosed diabetes who completed a physical examination as part of the 2003-2004 US National Health and Nutrition Examination Survey. RESULTS After adjusting for age, sex, race/ethnicity, income, lifestyle factors, total calcium, and energy intake, the odds ratio (OR) for MetSyn in the highest quintile of 25(OH)D (median 88.0 nmol/l) compared with the lowest quintile (median 26.8 nmol/l) was 0.27 (0.15, 0.46; P(trend)<0.001). This relation was unchanged after additional adjustment for PTH level (OR, 0.26; 0.15, 0.44; P(trend)<0.001) and did not differ by sex (P interaction 0.6) or age (< or > or =50 years; P interaction 0.2). In contrast, the multivariable-adjusted odds for MetSyn increased with increasing PTH among older men (P(trend) 0.004), but not younger men (P(trend) 0.4) or women regardless of age (P(trend) 0.4 in younger and older women). CONCLUSIONS These data suggest an inverse association of 25(OH)D with MetSyn, independent of potential confounding factors, calcium intake, and PTH, and a positive association of PTH with MetSyn among older men.

Descriptive epidemiology of pedometer-determined physical activity

PURPOSE The dual purposes of this study were: 1) to provide preliminary descriptive epidemiology data representing pedometer-determined physical activity (PA) and 2) to explore sources of intra-individual variability in steps per day. METHODS All participants (76 males, age = 48.4 +/- 16.3 yr, body mass index (BMI) = 27.1 +/- 5.1 kg x m(-2); 133 females, age = 47.4 +/- 17.5 yr, BMI = 26.9 +/- 5.7 kg x m(-2)) resided in Sumter County, SC, and were recruited by telephone to receive a mailed kit to self-monitor PA for 1 wk. Statistical analyses compared mean steps per day between sexes, races, age groups, education and income levels, and BMI categories. Mean steps per day were also compared between: 1) weekdays versus weekend days, 2) workdays versus nonworkdays, and 3) days of sport/exercise versus no participation. RESULTS The entire sample took 5931 +/- 3664 steps x d(-1) (males = 7192 +/- 3596 vs females = 5210 +/- 3518 steps x d(-1), t = 7.88, P < 0.0001). Significant differences were also indicated by race, age, education, income, and BMI. In addition, weekdays were significantly higher than weekend days, workdays were higher than nonworkdays, and sport/exercise days were higher than nonsport/exercise days. CONCLUSIONS The large standard deviations reflect a wide distribution of ambulatory behavior. Regardless, important differences are still evident by demographic characteristics, BMI categories, day of the week, and reported engagement in work or sport/exercise.

Association of Fitness in Young Adulthood With Survival and Cardiovascular Risk: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

IMPORTANCE Although cardiorespiratory fitness (CRF) is prognostic in older adults, the effect of CRF during early adulthood on long-term cardiovascular structure, function, and prognosis is less clear. OBJECTIVE To examine whether CRF in young adults is associated with long-term clinical outcome and subclinical cardiovascular disease (CVD). DESIGN, SETTING, AND PARTICIPANTS Prospective study of 4872 US adults aged 18 to 30 years who underwent treadmill exercise testing at a baseline study visit from March 25, 1985, to June 7, 1986, and 2472 individuals who underwent a second treadmill test 7 years later. Median follow-up was 26.9 years, with assessment of obesity, left ventricular mass and strain, coronary artery calcification (CAC), and vital status and incident CVD. Follow-up was complete on August 31, 2011, and data were analyzed from recruitment through the end of follow-up. MAIN OUTCOMES AND MEASURES The presence of CAC was assessed by computed tomography at years 15 (2000-2001), 20 (2005-2006), and 25 (2010-2011), and left ventricular mass was assessed at years 5 (1990-1991) and 25 (with global longitudinal strain). Incident CVD and all-cause mortality were adjudicated. RESULTS Of the 4872 individuals, 273 (5.6%) died and 193 (4.0%) experienced CVD events during follow-up. After comprehensive adjustment, each additional minute of baseline exercise test duration was associated with a 15% lower hazard of death (hazard ratio [HR], 0.85; 95% CI, 0.80-0.91; P < .001) and a 12% lower hazard of CVD (HR, 0.88; 95% CI, 0.81-0.96; P = .002). Higher levels of baseline CRF were associated with significantly lower left ventricular mass index (β = -0.24; 95% CI, -0.45 to -0.03; P = .02) and significantly better lobal longitudinal strain (β = -0.09; 95% CI, -0.14 to -0.05; P < .001) at year 25. Fitness was not associated with CAC. A 1-minute reduction in fitness by year 7 was associated with 21% and 20% increased hazards of death (HR, 1.21; 95% CI, 1.07-1.37; P = .002) and CVD (HR, 1.20; 95% CI, 1.06-1.37; P = .006), respectively, along with a more impaired strain (β = 0.15; 95% CI, 0.08-0.23; P < .001). No association between change in fitness and CAC was found. CONCLUSIONS AND RELEVANCE Higher levels of fitness at baseline and improvement in fitness early in adulthood are favorably associated with lower risks for CVD and mortality. Fitness and changes in fitness are associated with myocardial hypertrophy and dysfunction but not CAC. Regular efforts to ascertain and improve CRF in young adulthood may play a critical role in promoting cardiovascular health and interrupting early CVD pathogenesis.

Serum vitamin D, parathyroid hormone levels, and carotid atherosclerosis

Evidence suggests low vitamin D and elevated parathyroid hormone (PTH) concentrations may increase risk for cardiovascular disease. However, little is known about the association between vitamin D or PTH and subclinical atherosclerosis. This cross-sectional study included 654 community-dwelling older adults aged 55-96 years (mean age, 75.5 years) without a history of coronary heart disease, revascularization, or stroke enrolled in the Rancho Bernardo Study who completed a clinic examination in 1997-1999 and provided a blood sample for determination of serum 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)(2)D], and PTH concentrations. Carotid artery intima-media wall thickness (IMT) was measured as an indicator of atherosclerosis at two sites with B-mode ultrasound. After adjusting for age, sex, smoking, alcohol intake, waist-to-hip ratio, exercise, season of blood draw, diabetes, and hypertension, geometric mean internal carotid IMT (p(trend) 0.022), but not common carotid IMT (p(trend) 0.834) decreased in a dose-dependent fashion with increasing concentration of 25(OH)D. There was no association of 1,25(OH)(2)D or PTH with either measure of carotid IMT. In subgroup analyses, 1,25(OH)(2)D was inversely associated with internal carotid IMT among those with hypertension (p for interaction 0.036). These findings from a population-based cohort of older adults suggest a potential role for vitamin D in the development of subclinical atherosclerosis. Additional research is needed to determine whether vitamin D may influence the progression of atherosclerosis, including the effects of supplementation on the atherosclerotic process.

Comparison of Overall Obesity and Body Fat Distribution in Predicting Risk of Mortality

Results of studies comparing overall obesity and abdominal adiposity or body fat distribution with risk of mortality have varied considerably. We compared the relative importance and joint association of overall obesity and body fat distribution in predicting risk of mortality. Participants included 5,799 men and 6,429 women aged 30–102 years enrolled in the third National Health and Nutrition Examination Survey who completed a baseline health examination during 1988–1994. During a 12‐year follow‐up (102,172 person‐years), 1,188 men and 925 women died. In multivariable‐adjusted analyses, waist‐to‐thigh ratio (WTR) in both sexes (Ptrend <0.01 for both) and waist‐to‐hip ratio (WHR) in women (Ptrend 0.001) were positively associated with mortality in middle‐aged adults (30–64 years), while BMI and waist circumference (WC) exhibited U‐ or J‐shaped associations. Risk of mortality increased with a higher WHR and WTR among normal weight (BMI 18.5–24.9 kg/m2) and obese (BMI ≥30.0 kg/m2) adults. In older adults (65–102 years), a higher BMI in both sexes (Ptrend <0.05) and WC in men (Ptrend 0.001) were associated with increased survival, while remaining measures of body fat distribution exhibited either no association or an inverse relation with mortality. In conclusion, ratio measures of body fat distribution are strongly and positively associated with mortality and offer additional prognostic information beyond BMI and WC in middle‐aged adults. A higher BMI in both sexes and WC in men were associated with increased survival in older adults, while a higher WHR or WTR either decreased or did not influence risk of death.

Association Between Duration of Overall and Abdominal Obesity Beginning in Young Adulthood and Coronary Artery Calcification in Middle Age

IMPORTANCE Younger individuals are experiencing a greater cumulative exposure to excess adiposity over their lifetime. However, few studies have determined the consequences of long-term obesity. OBJECTIVE To examine whether the duration of overall and abdominal obesity was associated with the presence and 10-year progression of coronary artery calcification (CAC), a subclinical predictor of coronary heart disease. DESIGN, SETTING, AND PARTICIPANTS Prospective study of 3275 white and black adults aged 18 to 30 years at baseline in 1985-1986 who did not initially have overall obesity (body mass index [BMI] ≥30) or abdominal obesity (men: waist circumference [WC] >102 cm; women: >88 cm) in the multicenter, community-based Coronary Artery Risk Development in Young Adults (CARDIA) study. Participants completed computed tomography scanning for the presence of CAC during the 15-, 20-, or 25-year follow-up examinations. Duration of overall and abdominal obesity was calculated using repeat measurements of BMI and WC, respectively, performed 2, 5, 7, 10, 15, 20, and 25 years after baseline. MAIN OUTCOMES AND MEASURES Presence of CAC was measured by computed tomography at the year 15 (2000-2001), year 20 (2005-2006), or year 25 (2010-2011) follow-up examinations. Ten-year progression of CAC (2000-2001 to 2010-2011) was defined as incident CAC in 2010-2011 or an increase in CAC score of 20 Agatston units or greater. RESULTS During follow-up, 40.4% and 41.0% developed overall and abdominal obesity, respectively. Rates of CAC per 1000 person-years were higher for those who experienced more than 20 years vs 0 years of overall obesity (16.0 vs 11.0, respectively) and abdominal obesity (16.7 vs 11.0). Approximately 25.2% and 27.7% of those with more than 20 years of overall and abdominal obesity, respectively, experienced progression of CAC vs 20.2% and 19.5% of those with 0 years. After adjustment for BMI or WC and potential confounders, the hazard ratios for CAC for each additional year of overall or abdominal obesity were 1.02 (95% CI, 1.01-1.03) and 1.03 (95% CI, 1.02-1.05), respectively. The adjusted odds ratios for CAC progression were 1.04 (95% CI, 1.01-1.06) and 1.04 (95% CI, 1.01-1.07), respectively. Associations were attenuated but largely persisted following additional adjustment for potential intermediate metabolic factors during follow-up. CONCLUSIONS AND RELEVANCE Longer duration of overall and abdominal obesity was associated with subclinical coronary heart disease and its progression through midlife independent of the degree of adiposity. Preventing or at least delaying the onset of obesity in young adulthood may lower the risk of developing atherosclerosis through middle age.

Differences in vitamin D status as a possible contributor to the racial disparity in peripheral arterial disease

BACKGROUND Racial differences in cardiovascular risk factors do not fully explain the higher prevalence of lower-extremity peripheral arterial disease (PAD) in black adults. OBJECTIVE We sought to determine whether any of this excess risk may be explained by vitamin D status, which has been widely documented to be lower in blacks than in whites. DESIGN This population-based cross-sectional study included 2987 white and 866 black persons aged >or=40 y from the 2001-2004 National Health and Nutrition Examination Survey. PAD was defined as an ankle-brachial pressure index of <0.90 in either leg. RESULTS Mean (+/-SEM) 25-hydroxyvitamin D [25(OH)D] concentrations were significantly lower in black than in white adults (39.2 +/- 1.0 and 63.7 +/- 1.1 nmol/L, respectively; P < 0.001). Adjusted odds ratios for PAD decreased in a dose-dependent fashion with increasing quartiles of 25(OH)D in white adults [1.00 (referent), 0.86, 0.67, and 0.53; P for trend < 0.001]. In black adults, the association was nonlinear; models with cubic splines suggested evidence of greater odds for PAD and a trend for lower odds for PAD at the lowest and highest concentrations of 25(OH)D, respectively. After adjustment for racial differences in socioeconomic status and for traditional and novel risk factors, odds for PAD in black compared with white adults were reduced from 2.11 (95% CI: 1.55, 2.87) to 1.67 (1.11, 2.51). After additional adjustment for 25(OH)D, the odds were further reduced to 1.33 (0.84, 2.10). CONCLUSIONS Racial differences in vitamin D status may explain nearly one-third of the excess risk of PAD in black compared with white adults. Additional research is needed to confirm these findings.

Vitamin D in Atherosclerosis, Vascular Disease, and Endothelial Function

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.

Cardiovascular health through young adulthood and cognitive functioning in midlife

A study was undertaken to examine the association between overall cardiovascular health as recently defined by the American Heart Association in young adulthood to middle age and cognitive function in midlife. Overall ideal cardiovascular health incorporates 7 metrics, including the avoidance of overweight or obesity, a healthful diet, nonsmoking, and physical activity, total cholesterol, blood pressure, and fasting glucose at goal levels.