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1.  Obesity, Subclinical Myocardial Injury and Incident Heart Failure 
JACC. Heart failure  2014;2(6):600-607.
To evaluate the association of obesity with a novel biomarker of subclinical myocardial injury, cardiac troponin T measured with a new high sensitivity assay (hs-cTnT), among adults without clinical cardiovascular disease (CVD).
Laboratory evidence suggests a relationship between obesity andmyocardial injury that may play a role in the development of heart failure (HF), but there is limited clinical data regarding this association.
We evaluated 9,507 participants in the Atherosclerosis Risk in Communities Study without baseline CVD (Visit 4, 1996-1999). We assessed the cross sectional association of body-mass index (BMI) with high (≥14 ng/L) and measurable (≥3 ng/L) hs-cTnT levels after multivariable regression. We further evaluated the independent and combined associations of BMI and hs-cTnT with incident HF.
Higher BMI was independently associated with a positive, linear increase in the likelihood of high hs-cTnT, with severe obesity (BMI >35 kg/m2) associated with an odds ratio of 2.20 (95% CI: 1.59-3.06) for high hs-cTnT after adjustment. Over 12 years of follow-up, there were 869 incident HF events. Obesity and hs-cTnT were both independently associated with incident HF, and individuals with severe obesity and high hs-cTnT had a greater than 9-fold higher risk of incident HF (HR 9.20 [95% CI: 5.67-14.93]) than individuals with normal weight and undetectable hs-cTnT.
Among individuals without CVD, higher BMI has an independent, linear association with subclinical myocardial injury, as assessed by hs-cTnT levels. Obesity and hscTnT provide independent and complementary prognostic information regarding the risk of incident HF.
PMCID: PMC4345168  PMID: 25443112
obesity; heart failure; epidemiology; troponin
2.  High Sensitivity Troponin T and Cardiovascular Events in Systolic Blood Pressure Categories: Atherosclerosis Risk In Communities Study 
Hypertension  2014;65(1):78-84.
Based on observational studies there is a linear increase in cardiovascular risk with higher systolic blood pressure, yet clinical trials have not shown benefit across all systolic blood pressure categories. We assessed if troponin-T measured using high-sensitivity assay was associated with cardiovascular disease within systolic blood pressure categories in 11191 Atherosclerosis Risk in Communities study participants. Rested sitting systolic blood pressure by 10-mmHg increments and troponin categories were identified. Incident heart failure hospitalization, coronary heart disease and stroke were ascertained over a median of 12 years after excluding individuals with corresponding disease. Approximately 53% of each type of cardiovascular event occurred in individuals with systolic blood pressure<140 mmHg and troponin-T≥3ng/L. Higher troponin-T was associated with increasing cardiovascular events across most systolic blood pressure categories. The association was strongest for heart failure and least strong for stroke. There was no similar association of systolic blood pressure with cardiovascular events across troponin-T categories. Individuals with troponin-T≥3ng/L and systolic blood pressure<140mmHg had higher cardiovascular risk compared to those with troponin-T<3ng/L and systolic blood pressure 140-159 mmHg.
Higher troponin-T levels within narrow systolic blood pressure categories portend increased cardiovascular risk, particularly for heart failure. Individuals with lower systolic blood pressure but measurable troponin-T had greater cardiovascular risk compared to those with suboptimal systolic blood pressure but undetectable troponin-T. Future trials of systolic hypertension may benefit by using high-sensitivity troponin-T to target high-risk patients.
PMCID: PMC4268376  PMID: 25350984
High-sensitivity troponin-T; Hypertension; Atherosclerosis Risk In Communities (ARIC) Study; Cardiovascular disease; Heart failure
3.  NH2-Terminal Pro–Brain Natriuretic Peptide and Risk of Diabetes 
Diabetes  2013;62(9):3189-3193.
Brain natriuretic peptide (BNP) has an established role in cardiovascular disease (CVD). However, recent animal studies suggest direct metabolic effects of BNP. To determine the association of BNP with the risk of diabetes, we conducted a prospective analysis of participants from the Atherosclerosis Risk in Communities (ARIC) study. We included 7,822 men and women without history of diabetes, CVD, or reduced kidney function at baseline. At baseline, NH2-terminal (NT)-proBNP, a cleavage product of BNP, was inversely associated with adiposity, fasting glucose, insulin, and cholesterol but positively associated with blood pressure and C-reactive protein levels. During a median follow-up of 12 years, 1,740 participants reported a new diagnosis of diabetes or medication use for diabetes. Baseline quartiles of NT-proBNP were inversely associated with diabetes risk, even after multivariable adjustment including fasting glucose. The adjusted HRs for diabetes were 1.0 (reference), 0.84 (95% CI 0.74–0.96), 0.79 (95% CI 0.68–0.90), and 0.75 (95% CI 0.64–0.87) for the 1st, 2nd, 3rd, and 4th quartiles of baseline NT-proBNP, respectively (P for trend <0.001). This inverse association was robust across sex, race, and obesity subgroups. Our results extend animal studies and support a direct and important metabolic role of BNP in humans.
PMCID: PMC3749338  PMID: 23733199
4.  The Association of Framingham and Reynolds Risk Scores with Incidence and Progression of Coronary Artery Calcification in the Multi-Ethnic Study of Atherosclerosis 
To compare the association of the Framingham Risk Score (FRS) and Reynolds Risk Score (RRS) with subclinical atherosclerosis, assessed by incidence and progression of coronary artery calcium (CAC).
The comparative effectiveness of competing risk algorithms for indentifying subclinical atherosclerosis is unknown.
The Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective cohort study of 6,814 participants free of baseline CVD. All participants underwent risk factor assessment, as well as baseline and follow-up CAC testing. We assessed the performance of the FRS and RRS to predict CAC incidence and progression using relative risk and robust linear regression.
The study population included 5,140 individuals (61±10 years, 47% males, mean follow-up: 3.1±1.3 years). Among 53% of subjects (n=2,729) with no baseline CAC, 18% (n=510) developed incident CAC. Both the FRS and RRS were significantly predictive of incident CAC [RR 1.40 (95% CI 1.29 – 1.52), and RR 1.41 (95% CI 1.30 – 1.54) per 5% increase in risk, respectively] and CAC progression [mean CAC score change 6.92 (95% CI 5.31 – 8.54) and 6.82 (95% CI 5.51 – 8.14) per 5% increase]. Discordance in risk category classification (< or > 10% 10-year CHD risk) occurred in 13.7%, with only the RRS consistently adding predictive value for incidence and progression of CAC. These subclinical atherosclerosis findings are supported by a CHD events analysis over 5.6±0.7 year follow-up.
Both the RRS and FRS predict onset and progression of subclinical atherosclerosis. However, the RRS may provide additional predictive information when discordance between the scoring systems exists.
PMCID: PMC4079464  PMID: 22051329
coronary artery calcium progression; subclinical atherosclerosis; risk prediction; Reynolds Risk Score; Framingham Risk Score
5.  Hepatic Steatosis, Obesity and the Metabolic Syndrome Are Independently and Additively Associated With Increased Systemic Inflammation 
To assess the independent and collective associations of hepatic steatosis, obesity, and the metabolic syndrome with elevated high-sensitivity CRP (hs-CRP) levels.
Methods and Results
We evaluated 2,388 individuals without clinical cardiovascular disease between December 2004 and December 2006. Hepatic steatosis was diagnosed by ultrasound, and the metabolic syndrome was defined using NHLBI criteria. The cutpoint of ≥ 3 mg/L was used to define “high” hs-CRP. Multivariate logistic regression was used to assess the independent and collective associations of hepatic steatosis, obesity, and the metabolic syndrome with high hs-CRP. Steatosis was detected in 32% of participants, 23% met criteria for metabolic syndrome, and 17% of individuals were obese. After multivariate regression, hepatic steatosis (OR 2.07; 95% CI: 1.68-2.56), obesity (OR 3.00; 95% CI: 2.39-3.80), and the metabolic syndrome (2.39; 95% CI: 1.88-3.04) were all independently associated with high hs-CRP. Combinations of these factors were associated with an additive increase in the odds of high hs-CRP, with individuals with 1, 2, and 3 factors having ORs for high hs-CRP of 1.92 (1.49-2.48), 3.38 (2.50-4.57) and 4.53 (3.23-6.35), respectively.
Hepatic steatosis, obesity, and the metabolic syndrome are independently and additively associated with increased odds of high hs-CRP levels.
PMCID: PMC3148106  PMID: 21546603
Hepatic Steatosis; Obesity; Metabolic Syndrome; Inflammation; Cytokines
6.  Usefulness of Baseline Obesity to Predict Development of a High Ankle Brachial Index (From the Multi-Ethnic Study of Atherosclerosis) 
The American journal of cardiology  2011;107(9):1386-1391.
An abnormally high ankle brachial index (ABI) is associated with increased all-cause and cardiovascular mortality. The relationship of obesity to incident high-ABI has not been characterized. We investigated the hypothesis that increased obesity—quantified by body weight, BMI, waist circumference, and waist-to-hip-ratio—is positively associated with a high-ABI (ABI ≥ 1.3) and with mean ABI increases over a four year follow-up. Prevalence and incidence ratios for a high-ABI were obtained for 6540 and 5045 participants respectively in the Multi-Ethnic Study of Atherosclerosis (MESA), using log-binomial regression models adjusted for demographic, cardiovascular, and inflammatory/novel risk factors. Linear regression was used to analyze mean ABI change. Both prevalence and incidence of a high-ABI were significantly higher for the highest versus the lowest quartile of every baseline measure of obesity, with weight and BMI demonstrating the highest incidence ratios (2.7 and 2.4, respectively). All prevalence and incidence ratios were positive and graded across obesity quartiles, and were persistent in the subpopulation without diabetes. Among those with normal baseline ABI values, one MESA-standard deviation increase in every baseline measure of obesity was associated with significant increases in mean ABI values. In conclusion, we observed an independent, positive and graded association of increasing obesity to both prevalent and incident high-ABI, and to mean increases in ABI values over time. Weight and BMI seemed to be at least as strongly, if not more strongly, associated with a high-ABI than were measures of abdominal obesity.
PMCID: PMC3079000  PMID: 21377643
obesity; anthropometric measures; peripheral vascular disease; ankle-brachial index; epidemiology

Results 1-6 (6)