PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (31)
 

Clipboard (0)
None

Select a Filter Below

Year of Publication
1.  Are We Moving Towards Concordance on the Principle That Lipid Discordance Matters? 
Circulation  2013;129(5):539-541.
doi:10.1161/CIRCULATIONAHA.113.007207
PMCID: PMC4286869  PMID: 24345401
Editorials; coronary disease; lipids; lipoproteins; low-density lipoprotein cholesterol
2.  Headed in the Right Direction But at Risk for Miscalculation 
The newly released 2013 ACC/AHA Guidelines for Assessing Cardiovascular Risk makes progress compared with previous cardiovascular risk assessment algorithms. For example, the new focus on total atherosclerotic cardiovascular diseases (ASCVD) is now inclusive of stroke in addition to hard coronary events, and there are now separate equations to facilitate estimation of risk in non-Hispanic white and black individuals and separate equations for women. Physicians may now estimate lifetime risk in addition to 10-year risk. Despite this progress, the new risk equations do not appear to lead to significantly better discrimination than older models. Because the exact same risk factors are incorporated, using the new risk estimators may lead to inaccurate assessment of atherosclerotic cardiovascular risk in special groups such as younger individuals with unique ASCVD risk factors. In general, there appears to be an overestimation of risk when applied to modern populations with greater use of preventive therapy, although the magnitude of overestimation remains unclear. Because absolute risk estimates are directly used for treatment decisions in the new cholesterol guidelines, these issues could result in overuse of pharmacologic management. The guidelines could provide clearer direction on which individuals would benefit from additional testing, such as coronary calcium scores, for more personalized preventive therapies. We applaud the advances of these new guidelines, and we aim to critically appraise the applicability of the risk assessment tools so that future iterations of the estimators can be improved to more accurately assess risk in individual patients.
doi:10.1016/j.jacc.2014.04.010
PMCID: PMC4280905  PMID: 24814487
coronary artery calcium; guidelines; preventive cardiology; risk assessment
3.  Vitamin D and Subclinical Cerebrovascular Disease 
JAMA neurology  2014;71(7):863-871.
IMPORTANCE
Vitamin D deficiency has been associated with hypertension, diabetes mellitus, and incident stroke. Little is known about the association between vitamin D and subclinical cerebrovascular disease.
OBJECTIVE
To examine the relationship of 25-hydroxyvitamin D (25[OH]D) levels with cerebrovascular abnormalities as assessed on brain magnetic resonance imaging (MRI) among participants of the Atherosclerosis Risk in Communities (ARIC) Brain MRI study.
DESIGN, SETTING, AND PARTICIPANTS
Participants were white and black adults aged 55 to 72 years with no history of clinical stroke who underwent a cerebral MRI at ARIC visit 3 (n = 1622) and a second cerebral MRI approximately 10 years later (n = 888).
EXPOSURES
The 25(OH)D level was measured by mass spectrometry at visit 3, with levels adjusted for calendar month and categorized using race-specific quartiles.
MAIN OUTCOMES AND MEASURES
The cross-sectional and prospective associations of 25(OH)D levels with white matter hyperintensities (WMHs) and MRI-defined infarcts were investigated using multivariable regression models.
RESULTS
The mean age of the participants was 62 years, 59.6% were women, and 48.6% were black. Lower 25(OH)D levels were not significantly associated with WMH score of severity, prevalent high-grade WMH score (≥3), or prevalent infarcts in cross-sectional, multivariable-adjusted models (all P > .05). Similarly, no significant prospective associations were found for lower 25(OH)D levels with change in WMH volume, incident high WMH score (≥3), or incident infarcts on the follow-up MRI, which occurred approximately 10 years later.
CONCLUSIONS AND RELEVANCE
A single measure of 25(OH)D was not cross-sectionally associated with WMH grade or prevalent subclinical infarcts and was not prospectively associated with WMH progression or subclinical brain infarcts seen on serial cerebral MRIs obtained approximately 10 years apart. These findings do not support optimizing vitamin D levels for brain health.
doi:10.1001/jamaneurol.2014.755
PMCID: PMC4218739  PMID: 24861877
4.  Current guidelines for high-density lipoprotein cholesterol in therapy and future directions 
Many studies have suggested that a significant risk factor for atherosclerotic cardiovascular disease (ASCVD) is low high-density lipoprotein cholesterol (HDL-C). Therefore, increasing HDL-C with therapeutic agents has been considered an attractive strategy. In the prestatin era, fibrates and niacin monotherapy, which cause modest increases in HDL-C, reduced ASCVD events. Since their introduction, statins have become the cornerstone of lipoprotein therapy, the benefits of which are primarily attributed to decrease in low-density lipoprotein cholesterol. Findings from several randomized trials involving niacin or cholesteryl ester transfer protein inhibitors have challenged the concept that a quantitative elevation of plasma HDL-C will uniformly translate into ASCVD benefits. Consequently, the HDL, or more correctly, HDL-C hypothesis has become more controversial. There are no clear guidelines thus far for targeting HDL-C or HDL due to lack of solid outcomes data for HDL specific therapies. HDL-C levels are only one marker of HDL out of its several structural or functional properties. Novel approaches are ongoing in developing and assessing agents that closely mimic the structure of natural HDL or replicate its various functions, for example, reverse cholesterol transport, vasodilation, anti-inflammation, or inhibition of platelet aggregation. Potential new approaches like HDL infusions, delipidated HDL, liver X receptor agonists, Apo A-I upregulators, Apo A mimetics, and gene therapy are in early phase trials. This review will outline current therapies and describe future directions for HDL therapeutics.
doi:10.2147/VHRM.S45648
PMCID: PMC3986285  PMID: 24748800
high-density lipoprotein; lipids; cholesterol; atherosclerosis; cardiovascular disease; therapy
6.  Vitamin D, Calcium, and Atherosclerotic Risk: Evidence from serum levels and supplementation studies 
Vitamin D and calcium have been 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.
doi:10.1007/s11883-012-0293-5
PMCID: PMC3531793  PMID: 23232985
calcium; vitamin D; supplements; cardiovascular disease; review
7.  Association Between Resting Heart Rate and Inflammatory Biomarkers (High-Sensitivity C-Reactive Protein, Interleukin-6, and Fibrinogen) (from the Multi-Ethnic Study of Atherosclerosis) 
The American journal of cardiology  2013;113(4):644-649.
Heart rate (HR) at rest is associated with adverse cardiovascular events; however, the biologic mechanism for the relation is unclear. We hypothesized a strong association between HR at rest and subclinical inflammation, given their common interrelation with the autonomic nervous system. HR at rest was recorded at baseline in the Multi-Ethnic Study of Atherosclerosis, a cohort of 4 racial or ethnic groups without cardiovascular disease at baseline and then divided into quintiles. Subclinical inflammation was measured using high-sensitivity C-reactive protein, interleukin-6, and fibrinogen. We used progressively adjusted regression models with terms for physical activity and atrioventricular nodal blocking agents in the fully adjusted models. We examined inflammatory markers as both continuous and categorical variables using the clinical cut point of ≥3 mg/L for high-sensitivity C-reactive protein and the upper quartiles of fibrinogen (≥389 mg/dl) and interleukin-6 (≥1.89 pg/ml). Participants had a mean age of 62 years (SD 9.7), mean resting heart rate of 63 beats/min (SD 9.6) and were 47% men. Increased HR at rest was significantly associated with higher levels of all 3 inflammatory markers in both continuous (p for trend <0.001) and categorical (p for trend <0.001) models. Results were similar among all 3 inflammatory markers, and there was no significant difference in the association among the 4 racial or ethnic groups. In conclusion, an increased HR at rest was associated with a higher level of inflammation among an ethnically diverse group of subjects without known cardiovascular disease.
doi:10.1016/j.amjcard.2013.11.009
PMCID: PMC4280910  PMID: 24393259
8.  25(OH)D deficiency is associated with fatal stroke among whites but not blacks: The NHANES-III linked mortality files 
Objective
Deficient 25-hydroxyvitamin D [25(OH)D] levels are associated with cardiovascular disease (CVD) events and mortality. Both 25(OH)D deficiency and stroke are more prevalent among blacks. We examined whether low 25(OH)D contributes to the excess risk of fatal stroke in blacks compared to whites.
Research Methods and Procedures
The Third National Health and Nutrition Examination Survey, a probability sample of US civilians, measured 25(OH)D levels and CVD risk factors between 1988–1994. Vital status through December 2006 was obtained via linkage with the National Death Index. Among white and black adults without CVD reported at baseline (n=7981), Cox regression models were fit to estimate hazard ratios (HR) for fatal stroke by 25(OH)D status and race.
Results
During a median of 14.1 years, there were 116 and 60 fatal strokes among whites and blacks respectively. The risk of fatal stroke was greater in blacks compared to whites in models adjusted for socio-economic status and CVD risk factors, [HR 1.60 (95% CI 1.01–2.53)]. Mean baseline 25(OH)D levels were significantly lower in blacks compared to whites (19.4 vs 30.8 ng/mL, respectively). In multivariable-adjusted models, deficient 25(OH)D levels <15 ng/mL were associated with fatal stroke among whites [HR 2.13 (1.01–4.50)] but not blacks [HR 0.93 (0.49–1.80)].
Conclusions
Vitamin D deficiency was associated with increased risk of stroke death in whites but not blacks. Although blacks had a higher rate of fatal stroke compared to whites, the low 25(OH)D levels in blacks were unrelated to stroke incidence and therefore 25(OH)D levels did not explain this excess risk.
doi:10.1016/j.nut.2011.10.015
PMCID: PMC3304002  PMID: 22261577
vitamin D; stroke; racial differences
9.  Vitamin D Status and Cardiometabolic Risk Factors in the US Adolescent Population 
Pediatrics  2009;124(3):e371-e379.
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(OH)D] are associated with cardiovascular risk factors in US adolescents aged 12–19 years.
METHODS
Cross-sectional analysis of 3,577 fasting, nonpregnant adolescents without diagnosed diabetes who participated in the 2001–2004 National Health and Nutrition Examination Survey (NHANES). Risk factors for cardiovascular disease measured using standard methods and defined according to age-modified Adult Treatment Panel-III definitions.
RESULTS
Mean 25(OH)D in US adolescents was 24.8 ng/mL; 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<0.001, for each pair-wise comparison). Low 25(OH)D levels were strongly associated with overweight status and abdominal obesity (ptrend<0.001, for both). Following adjustment for age, sex, race/ethnicity, body mass index, socioeconomic status, and physical activity, 25(OH)D levels were inversely associated with systolic blood pressure (p=0.02) and plasma glucose concentrations (p=0.01). The adjusted odds ratio (95% CI) for those in the lowest (<15 ng/mL) compared to the highest quartile (>26 ng/mL) of 25(OH)D for hypertension was 2.36 (1.33, 4.19); for fasting hyperglycemia 2.54 (1.01, 6.40); for low HDL-cholesterol 1.54 (0.99, 2.39); for hypertriglyceridemia 1.00 (0.49, 2.04); and for metabolic syndrome 3.88 (1.57, 9.58).
CONCLUSIONS
Low serum vitamin D in US adolescents is strongly associated with an increased prevalence of hypertension, hyperglycemia, and metabolic syndrome, independent of adiposity. Whether the low concentrations of vitamin D among adolescents predicts future adverse health events remains to be determined.
doi:10.1542/peds.2009-0213
PMCID: PMC4222068  PMID: 19661053
cardiovascular; children; dietary supplements
10.  25-hydroxyvitamin D and parathyroid hormone are not associated with carotid intima-media thickness or plaque in the Multi-Ethnic Study of Atherosclerosis 
Objective
Observational evidence supports independent associations between 25-hydroxyvitamin D (25-OHD), parathyroid hormone (PTH) and cardiovascular risk. A plausible hypothesis for these associations is accelerated development of atherosclerosis.
Approach and Results
We evaluated cross-sectional and longitudinal associations of 25-OHD and PTH with carotid intima-media thickness (IMT) and carotid plaques among 3251 participants free of cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis. 25-OHD and PTH were measured at baseline by mass spectrometry and immunoassay, respectively. All subjects underwent a carotid ultrasound exam at baseline and 9.4 years later (median, range 8–11.1y). Multivariable linear and logistic regressions were used to test associations of 25-OHD and PTH with the extent and the progression of IMT and the prevalence and incidence of carotid plaque. Mean (SD) 25-OHD and PTH were 25.8ng/ml (10.6) and 44.2pg/ml (20.2). No independent associations were found between 25-OHD or PTH and IMT at baseline [increment of 1.9µm (95%CI −5.1 to 8.9) per 10ng/ml lower 25-OHD; increment of 0.8µm (95%CI −3.2 to 4.8) per 10pg/ml higher PTH] or progression of IMT [increment of 2.6µm (95%CI −2.5 to 7.8) per 10ng/ml lower 25-OHD, increment of 1.6µm (95%CI −1.9 to 5.2) per 10pg/ml higher PTH]. No associations were found with the baseline prevalence of carotid plaque or the incidence of new plaques over the study period. We did not observe any interaction by race or ethnicity (White, Chinese, Black and Hispanic).
Conclusions
The consistent lack of association of vitamin D and PTH with carotid IMT and plaque suggests that these hormones may influence cardiovascular risk through pathways not reflected by carotid atherosclerosis.
doi:10.1161/ATVBAHA.113.301781
PMCID: PMC3956469  PMID: 23814117
vitamin D; PTH; mineral metabolism; intima-media thickness; plaque; atherosclerosis; carotid
11.  Should Statin Therapy Be Allocated on the Basis of Global Risk or on the Basis of Randomized Trial Evidence? 
The American journal of cardiology  2010;106(6):905-909.
Current clinical guidelines recommend the use of a global risk assessment tool, such as those pioneered by the Framingham Heart Study, to determine eligibility for statin therapy in patients with absolute risk levels greater than a certain threshold. In support of this approach, several randomized trials have reported that patients with high absolute risk clearly benefit from statin therapy. Therefore, the guideline recommendations would seem intuitive and effective, albeit on the core assumption that the mortality and morbidity benefits associated with statin therapy would be greatest in those with high predicted absolute risk. However, if this assumption is incorrect, using predicted absolute risk to guide statin therapy could easily result in underuse in some groups and overuse in others. Herein, the authors question the utility of global risk assessment strategies based on the Framingham risk score for guiding statin therapy in light of current data that have become available from more recent and robust prospective randomized clinical trials since the publication of the National Cholesterol Education Program Adult Treatment Panel III guidelines. Moreover, the Adult Treatment Panel III guidelines do not support treatment of some patients who may benefit from statin therapy. In conclusion, the authors propose an alternative approach for incorporating more recent randomized trial data into future statin allocation algorithms and treatment guidelines.
doi:10.1016/j.amjcard.2010.05.015
PMCID: PMC4201182  PMID: 20816135
12.  Association between Anxiety Levels and Weight Change in the Multiethnic Study of Atherosclerosis 
Journal of Obesity  2014;2014:894627.
Objective. To examine the association between anxiety and weight change in a multiethnic cohort followed for approximately 10 years. Methods. The study population consisted of participants of the multiethnic study of atherosclerosis who met specified inclusion criteria (n = 5,799). Weight was measured at baseline and four subsequent follow-up exams. Anxiety was analyzed as sex-specific anxiety quartiles (QANX). The relationship between anxiety level and weight change was examined using a mixed-effect model with weight as the dependent variable, anxiety and time as the independent variables, and adjusted for covariates. Results. Average annual weight change (range) was −0.17 kg (−6.04 to 4.38 kg) for QANX 1 (lowest anxiety), −0.16 kg (−10.71 to 4.45 kg) for QANX 2, −0.15 kg (−8.69 to 6.39 kg) for QANX 3, and −0.20 kg (−7.12 to 3.95 kg) for QANX 4 (highest anxiety). No significant association was noted between QANX and weight change. However, the highest QANX was associated with a −2.48 kg (95% CI = −3.65, −1.31) lower baseline weight compared to the lowest QANX after adjustment for all covariates. Conclusions. Among adults, age 45–84, higher levels of anxiety, defined by the STPI trait anxiety scale, are associated with lower average baseline weight but not with weight change.
doi:10.1155/2014/894627
PMCID: PMC4206924  PMID: 25374677
13.  Clinical utility of rosuvastatin and other statins for cardiovascular risk reduction among the elderly 
Age is one of the strongest predictors of cardiovascular disease (CVD) risk. Treatment with statins can significantly reduce CVD events and mortality in both primary and secondary prevention. Yet despite the high CVD risk among the elderly, there is underutilization of statins in this population (ie, the treatment-risk paradox). Few studies have investigated the use of statins in the elderly, particularly for primary prevention and, as a result, guidelines for treating the elderly are limited. This is likely due to: uncertainties of risk assessment in older individuals where the predictive value of individual risk factors is decreased; the need to balance the benefits of primary prevention with the risks of polypharmacy, health care costs, and adverse medication effects in a population with decreased life expectancy; the complexity of treating patients with many other comorbidities; and increasingly difficult social and economic concerns. As life expectancy increases and the total elderly population grows, these issues become increasingly important. JUPITER (Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) is the largest primary prevention statin trial to date and enrolled a substantial number of elderly adults. Among the 5695 JUPITER participants ≥70 years of age, the absolute CVD risk reduction associated with rosuvastatin was actually greater than for younger participants. The implications of this JUPITER subanalysis and the broader role of statins among older adults is the subject of this review.
doi:10.2147/CIA.S8101
PMCID: PMC3066250  PMID: 21472089
JUPITER; rosuvastatin; elderly; risk
14.  Fibroblast Growth Factor‐23 and Incident Coronary Heart Disease, Heart Failure, and Cardiovascular Mortality: The Atherosclerosis Risk In Communities Study 
Background
Fibroblast growth factor‐23 (FGF‐23) is a hormone involved in phosphorous regulation and vitamin D metabolism that may be associated with cardiovascular risk, and it is a potential target for intervention. We tested whether elevated FGF‐23 is associated with incident coronary heart disease, heart failure, and cardiovascular mortality, even at normal kidney function.
Methods and Results
A total of 11 638 Atherosclerosis Risk In Communities study participants, median age 57 at baseline (1990–1992), were followed through 2010. Cox regression was used to evaluate the independent association of baseline serum active FGF‐23 with incident outcomes. Models were adjusted for traditional cardiovascular risk factors and estimated glomerular filtration rate. During a median follow‐up of 18.6 years, 1125 participants developed coronary heart disease, 1515 developed heart failure, and 802 died of cardiovascular causes. For all 3 outcomes, there was a threshold, whereby FGF‐23 was not associated with risk at <40 pg/mL but was positively associated with risk at >40 pg/mL. Compared with those with FGF‐23 <40 pg/mL, those in the highest FGF‐23 category (≥58.8 pg/mL) had a higher risk of incident coronary heart disease (adjusted hazard ratio, 95% CIs: 1.65, 1.40 to 1.94), heart failure (1.75, 1.52 to 2.01), and cardiovascular mortality (1.65, 1.36 to 2.01). Associations were modestly attenuated but remained statistically significant after further adjustment for estimated glomerular filtration rate. In stratified analyses, similar results were observed in African Americans and among persons with normal kidney function.
Conclusions
High levels of serum FGF‐23 were associated with increased risk of coronary heart disease, heart failure, and cardiovascular mortality in this large, biracial, population‐based cohort. This association was independent of traditional cardiovascular risk factors and kidney function.
doi:10.1161/JAHA.114.000936
PMCID: PMC4309096  PMID: 24922628
Atherosclerosis Risk In Communities; cardiovascular mortality; coronary heart disease; epidemiology; fibroblast growth factor 23; heart failure
15.  Factors Associated With Low Levels of Subclinical Vascular Disease in Older Adults: Multi-Ethnic Study of Atherosclerosis 
Preventive cardiology  2009;12(2):72-79.
Coronary artery calcium (CAC), carotid intimal medial thickness (cIMT), and reduced ankle brachial indices (ABI) are markers of subclinical vascular disease strongly associated with aging. We identified factors associated with low levels of subclinical vascular disease in 1824 participants ≥70 years in the Multi-Ethnic Study of Atherosclerosis. 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 three parameters. This combination index was independently associated with younger age [OR=2.5 per 1 SD (95%CI 1.8–3.6)], female gender [OR=3.0(1.9–4.8)], lower BMI [OR=1.6 per 1 SD (1.2–2.0)], absence of hypertension [OR=1.8(1.2–2.6)], absence of dyslipidemia [OR=1.6 (1.04–2.4)], and never smoking [OR=1.7(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.
doi:10.1111/j.1751-7141.2008.00023.x
PMCID: PMC2932469  PMID: 19476580
16.  Serum 25-hydroxyvitamin D levels are not associated with subclinical vascular disease or C-reactive protein in the Old Order Amish 
Calcified tissue international  2009;84(3):195-202.
Background
The relationship between vitamin D metabolites and subclinical vascular disease is controversial. Because low serum levels of 25-hydroxyvitamin D [25(OH)D] have been associated with many cardiovascular disease (CVD) risk factors, we hypothesized that serum 25(OH)D levels would be inversely associated with inflammation as measured by C-reactive protein (CRP) and with subclinical vascular disease as measured by carotid intimal medial thickness (cIMT) and coronary artery calcification (CAC).
Methods
We measured 25(OH)D levels in 650 Amish participants. CAC was measured by computed tomography, and cIMT by ultrasound. The associations of 25(OH)D levels with natural log(CAC+1), cIMT, and natural log(CRP) levels were estimated following adjustment for age, sex, family structure, and season of examination. Additional analyses were carried out adjusting for body mass index (BMI) and other CVD risk factors.
Results
25(OH)D deficiency (<20 ng/ml) and insufficiency (21-30 ng/ml) were common among the Amish (38.2% and 47.7%, respectively). 25(OH)D levels were associated with season, age, BMI, and parathyroid hormone levels. In neither the minimally or fully adjusted analyses were significant correlations observed between 25(OH)D levels and CAC, cIMT, or CRP (R2 < 0.01 for all).
Conclusion
Contrary to our hypothesis, this study failed to detect a cross-sectional association between serum 25(OH)D levels and CAC, cIMT, or CRP. Either there is no causal relationship between 25(OH)D and CVD risk, or, if there is, it may be mediated through mechanisms other than subclinical vascular disease severity.
doi:10.1007/s00223-008-9209-3
PMCID: PMC2908302  PMID: 19148561
17.  Pulmonary Hyperinflation and Left Ventricular Mass 
Circulation  2013;127(14):1503-1511e6.
Background
Left ventricular (LV) mass is an important predictor of heart failure and cardiovascular mortality, yet determinants of LV mass are incompletely understood. Pulmonary hyperinflation in chronic obstructive pulmonary disease (COPD) may contribute to changes in intrathoracic pressure that increase LV wall stress. We therefore hypothesized that residual lung volume in COPD would be associated with greater LV mass.
Methods and results
The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study recruited smokers aged 50–79 years who were free of clinical cardiovascular disease. LV mass was measured by cardiac magnetic resonance. Pulmonary function testing was performed according to guidelines. Regression models were used to adjust for age, sex, body size, blood pressure and other cardiac risk factors.
Among 119 MESA COPD Study participants, mean age was 69±6 years, 55% were male and 65% had COPD, mostly of mild or moderate severity. Mean LV mass was 128±34 grams. Residual lung volume was independently associated with greater LV mass (7.2 grams per standard deviation increase in residual volume; 95% CI 2.2 to 12; P=0.004), and was similar in magnitude to that of systolic blood pressure (7.6 grams per standard deviation increase in systolic blood pressure, 95% CI 4.3 to 11 grams; p<0.001). Similar results were observed for LV mass to end-diastolic volume ratio (p=0.02) and with hyperinflation measured as residual volume to total lung capacity ratio (P=0.009).
Conclusions
Pulmonary hyperinflation, as measured by residual lung volume or residual lung volume to total lung capacity ratio, is associated with greater LV mass.
doi:10.1161/CIRCULATIONAHA.113.001653
PMCID: PMC4018203  PMID: 23493320
Left ventricular mass; hyperinflation; chronic obstructive pulmonary disease
18.  The JUPITER and AURORA clinical trials for rosuvastatin in special primary prevention populations: perspectives, outcomes, and consequences 
Statins have emerged at the forefront of preventive cardiology and have significantly reduced cardiovascular events and mortality. Nonetheless, cardiovascular disease remains the leading cause of death in the United States and in other developed countries, as well as the etiology of significant morbidity and health-care expenditure. In an attempt to reduce potentially missed opportunities for instituting preventive therapy, the JUPITER study (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) and the AURORA study (A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis: An Assessment of Survival and Cardiovascular Events) examined the effect of statins in two specific patient populations who currently do not meet the guidelines for statin treatment, but nonetheless, are at high cardiovascular risk. This review outlines the JUPITER and AURORA trials, interprets the data and significance of the results, analyses the drawbacks and impact of both trials and delineates the potential for further clinical trials.
PMCID: PMC2801627  PMID: 20057896
JUPITER; AURORA; rosuvastatin; cardiovascular disease
19.  Sex Hormones, Sex Hormone Binding Globulin, and Abdominal Aortic Calcification in Women and Men in the Multi-Ethnic Study of Atherosclerosis (MESA) 
Atherosclerosis  2008;200(2):432-438.
Background
Conflicting findings exist regarding the associations of sex hormones with subclinical atherosclerosis.
Methods
This is a substudy from MESA of 881 postmenopausal women and 978 men who had both abdominal aortic calcification (AAC) quantified by computed tomography and sex hormone levels assessed [Testosterone (T), estradiol (E2), dehydroepiandrosterone (DHEA), and sex hormone binding globulin (SHBG)]. We examined the association of sex hormones with presence and extent of AAC.
Results
For women, SHBG was inversely associated with both AAC presence [OR=0.62, 95% CI 0.42 to 0.91 for 1 unit greater log(SHBG) level] and extent [0.29 lower log(AAC) for 1 unit greater log(SHBG) level, β= −0.29 (95% CI −0.57 to −0.006)] adjusting for age, race, hypertension, smoking, diabetes, BMI, physical activity, and other sex hormones. After further adjustment for total and HDL-cholesterol, SHBG was not associated with ACC presence or extent. In men, there was no association between SHBG and AAC. In both men and women, neither T, E2, nor DHEA was associated with AAC presence or extent.
Conclusion
After adjustment for non-lipid cardiovascular risk factors, SHBG levels are inversely associated with both the presence and severity of AAC in women but not in men, which may be accounted for by HDL.
doi:10.1016/j.atherosclerosis.2007.12.032
PMCID: PMC2607033  PMID: 18262187
sex hormone binding globulin; abdominal aortic calcification; sex hormones; subclinical atherosclerosis
20.  Impact of Fitness Versus Obesity on Routinely Measured Cardiometabolic Risk in Young, Healthy Adults 
The American journal of cardiology  2013;111(7):991-995.
Obesity demonstrates a direct relation with cardiovascular risk and all-cause mortality, while cardiorespiratory fitness demonstrates an inverse relation. In clinical practice, several cardiometabolic (“CM”) risk factors are commonly measured to gauge cardiovascular risk yet the interaction between fitness and obesity with regard CM risk has not been fully explored. We studied 2,634 Brazilian adults referred for an employer-sponsored heath exam. Obesity was defined as BMI >30 kg/m2 or waist circumference > 102cm (men) or >88cm (women) when BMI 25–30kg/m2. Fitness was quantified by stage achieved on an Ellestad treadmill stress test, with those completing stage 4 considered fit. Hepatic steatosis was determined by ultrasound. We compared CM risk factors after stratifying patients into 4 groups: fit/normal weight, fit/obese, unfit/normal weight & unfit/obese. Approximately 22% of patients were obese; 12% were unfit. Fitness and obesity were moderately correlated (ρ=0.38–50). 6.5% of the sample was unfit/normal weight, and 16% fit/obese. In overweight and obese patients, fitness was negatively associated with CM risk (p<0.01 for all values). In fit patients, increasing BMI was positively associated with CM risk (p<0.01 for all values). In instances of discordance between fitness and obesity, obesity was the stronger determinant of CM risk. Fitness and obesity are independently associated with CM risk. The effects of fitness and obesity are additive but obesity is more strongly associated with CM risk when fitness and obesity are discordant. These findings underscore the need for weight loss in obese individuals and suggest an unmeasured benefit of fitness.
doi:10.1016/j.amjcard.2012.12.022
PMCID: PMC3697077  PMID: 23340029
fitness; obesity; metabolic syndrome; liver fat; inflammation
21.  Narrowing Sex Differences in Lipoprotein Cholesterol Subclasses Following Mid‐Life: The Very Large Database of Lipids (VLDL‐10B) 
Background
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.
Methods and Results
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 each decade, for example 14% higher from their 30s to 50s, while HDL‐C concentrations did not differ. Women had more buoyant LDL‐C and HDL‐C (lower LLDR and LHDR) than men at all ages but the gap closed in higher age groups. In contrast, women had a generally denser VLDL‐C (higher LVDR) leading into midlife, with the gap progressively closing in higher age groups, approximating that of men in their 60s and 70s.
Conclusion
The narrowing sex differential in cardiovascular disease risk after midlife is mirrored by a higher total atherogenic lipoprotein cholesterol burden in women and a closer approximation of the less favorable density phenotype characteristic of men.
doi:10.1161/JAHA.114.000851
PMCID: PMC4187479  PMID: 24755154
aging; lipids; menopause; prevention; statins
22.  C-reactive protein level and the incidence of eligibility for statin therapy: the Multi-Ethnic Study of Atherosclerosis (MESA) 
Clinical cardiology  2012;36(1):15-20.
Introduction
Given the results of the JUPITER trial, statin initiation may be considered for individuals with elevated high sensitivity C-reactive protein (CRP). However, if followed prospectively, many individuals with elevated CRP may become statin-eligible, limiting the impact of elevated CRP as a treatment indication. This analysis estimates the proportion of people with elevated CRP that become statin eligible over time.
Methods
We followed 2,153 Multi-Ethnic Study of Atherosclerosis (MESA) participants free of cardiovascular disease (CVD) and diabetes with LDL-cholesterol (LDL-C) <130 mg/dL at baseline to determine the proportion who become eligible for statins over 4.5 years. The proportion eligible for statin therapy, defined by the National Cholesterol Education Program (NCEP) 2004 updated guidelines, was calculated at baseline and during follow-up stratified by baseline CRP level (≥2 mg/L).
Results
At baseline, 47% of the 2,153 participants had elevated CRP. Among participants with elevated CRP, 29% met NCEP criteria for statins, compared to 28% without elevated CRP at baseline. By 1.5 years later, 26% and 22% (p=0.09) of those with and without elevated CRP at baseline reached NCEP LDL-C criteria and/or had started statins, respectively. These increased to 42% and 39% (p=0.24) at 3 years and 59% and 52% (p=0.01) at 4.5 years following baseline.
Conclusions
A substantial proportion of those with elevated CRP did not achieve NCEP based statin eligibility over 4.5 years of follow-up. These findings suggest that many patients with elevated CRP may not receive the benefits of statins if CRP is not incorporated into the NCEP screening strategy.
doi:10.1002/clc.22046
PMCID: PMC3953418  PMID: 22886783
23.  Neighborhood health-promoting resources and obesity risk (the Multi-Ethnic Study of Atherosclerosis) 
Obesity (Silver Spring, Md.)  2013;21(3):10.1002/oby.20255.
While behavioral change is necessary to reverse the obesity epidemic, it can be difficult to achieve and sustain in unsupportive residential environments. This study hypothesized that environmental resources supporting walking and a healthy diet are associated with reduced obesity incidence. Data came from 4008 adults aged 45–84 at baseline who participated in a neighborhood ancillary study of the Multi-Ethnic Study of Atherosclerosis. Participants were enrolled at 6 study sites at baseline (2000–2002) and neighborhood scales were derived from a supplementary survey that asked community residents to rate availability of healthy foods and walking environments for a one-mile buffer area. Obesity was defined as body mass index (BMI) >=30 kg/m2. Associations between incident obesity and neighborhood exposure were examined using proportional hazards and generalized linear regression. Among 4008 non-obese participants, 406 new obesity cases occurred during 5 years of follow-up. Neighborhood healthy food environment was associated with 10% lower obesity incidence per standard deviation increase neighborhood score. The association persisted after adjustment for baseline BMI and individual level covariates (HR 0.88, 95% CI: 0.79, 0.97), and for correlated features of the walking environment but confidence intervals widened to include the null (HR 0.89, 95% CI: 0.77, 1.03). Associations between neighborhood walking environment and lower obesity were weaker and did not persist after adjustment for correlated neighborhood healthy eating amenities (HR 0.98, 95% CI 0.84, 1.15). Altering the residential environment so that healthier behaviors and lifestyles can be easily chosen may be a pre-condition for sustaining existing healthy behaviors and for adopting new healthy behaviors.
doi:10.1002/oby.20255
PMCID: PMC3511654  PMID: 23592671
Adult; Health Behavior; Obesity/*epidemiology; Residence Characteristics; Longitudinal Studies; Geographic Information Systems; Environment Design; Public Health; Risk Factors
24.  Association of Sex Hormones and SHBG with Depressive Symptoms in Post-menopausal Women: the Multi-Ethnic Study of Atherosclerosis 
Menopause (New York, N.y.)  2012;19(8):877-885.
Objective
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 (E2), dehydroepiandrosterone (DHEA) and sex hormone binding globulin (SHBG) with depressive symptoms stratified on postmenopausal stage to determine whether associations were strongest for early postmenopausal women.
Methods
Women (N=1824) free of depressive symptoms at baseline (2000–2002) in the Multi-Ethnic Study of Atherosclerosis were categorized into tertiles of years postmenopause: T1, 0–10 years; T2, 11–20 years; and T3, 21–58 years. Multivariable-adjusted relative risks (RR) and 95% confidence intervals 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).
Results
In analysis including all sex hormones, the RRs for incident depressive symptoms associated with 1 unit higher log(total T) was 0.57 (p=0.13), log(E2) was 0.78 (p=0.04), log(SHBG) was 1.84 (p=0.003) and log(DHEA) 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 non-users.
Conclusions
In women early postmenopause, sex hormones were associated with incident depressive symptoms.
doi:10.1097/gme.0b013e3182432de6
PMCID: PMC3376685  PMID: 22415566
sex hormones; CES-D; depression; testosterone; estradiol; SHBG
25.  Prediction of Coronary Artery Calcium Progression in Individuals with Low Framingham Risk Score: The Multi-Ethnic Study of Atherosclerosis (MESA) 
Jacc. Cardiovascular Imaging  2012;5(2):144-153.
Objectives
We sought to determine whether novel markers not involving ionizing radiation could predict CAC progression in a low-risk population.
Background
Increase in coronary artery calcium (CAC) scores over time (CAC progression) improves prediction of coronary heart disease (CHD) events. Due to radiation exposure, CAC measurement represents an undesirable method for repeated risk assessment, particularly in low predicted risk individuals (Framingham Risk Score [FRS] <10%).
Methods
From 6814 MESA participants, 2620 individuals were classified as low risk for CHD events (FRS <10%), and had follow-up CAC measurement. In addition to traditional risk factors [(RFs) - base model], various combinations of novel-marker models were selected based on data-driven, clinical, or backward stepwise selection techniques.
Results
Mean follow-up was 2.5 years. CAC progression occurred in 574 participants (22% overall; 214 of 1830 with baseline CAC =0, and 360 of 790 with baseline CAC >0). Addition of various combinations of novel markers to the base model (c-statistic =0.711), showed improvements in discrimination of approximately only 0.005 each (c-statistics 0.7158, 0.7160 and 0.7164) for the best-fit models. All 3 best-fit novel-marker models calibrated well but were similar to the base model in predicting individual risk probabilities for CAC progression. The highest prevalence of CAC progression occurred in the highest compared to the lowest probability quartile groups (39.2–40.3% versus 6.4–7.1%).
Conclusions
In individuals at low predicted risk by FRS, traditional RFs predicted CAC progression in the short term with good discrimination and calibration. Prediction improved minimally when various novel markers were added to the model.
doi:10.1016/j.jcmg.2011.11.008
PMCID: PMC3310187  PMID: 22340820
coronary calcium; Framingham risk score; risk factors; progression

Results 1-25 (31)