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Hepatic steatosis and cardiovascular disease outcomes: An analysis of the Framingham Heart Study.

ABSTRACT: BACKGROUND & AIMS:Non-alcoholic fatty liver disease (NAFLD) is highly prevalent and is associated with development of metabolic disease including atherosclerotic cardiovascular disease (CVD). Our aim is to examine the association of hepatic steatosis with prevalent clinical and subclinical CVD outcomes in a large community-based sample, the Framingham Heart Study. METHODS:Hepatic steatosis was measured in 3529 participants using multidetector computed tomography scanning. Multivariable logistic regression was used to determine whether hepatic steatosis is associated with prevalent CVD adjusted for covariates. We also tested whether associations were independent of other metabolic diseases/traits. The primary clinical outcome was composite prevalent clinical CVD defined by prior non-fatal myocardial infarction, stroke, transient ischemic attack, heart failure, or peripheral arterial disease. Subclinical cardiovascular outcomes were coronary artery calcium (CAC) and abdominal artery calcium (AAC). RESULTS:3014 participants were included (50.5% women). There was a non-significant association of hepatic steatosis with clinical CVD (OR 1.14 [p=0.07]). Hepatic steatosis was associated with both CAC and AAC (OR 1.20 [p<0.001] and OR 1.16 [p<0.001], respectively). Associations persisted for CAC even when controlling for other risk factors/metabolic diseases, but for AAC, the associations became non-significant after adjustment for visceral adipose tissue. The association between hepatic steatosis and AAC was stronger in men than in women (p sex interaction=0.022). CONCLUSION:There was a significant association of hepatic steatosis with subclinical CVD outcomes independent of many metabolic diseases/traits with a trend towards association between hepatic steatosis and clinical CVD outcomes. The association with AAC was stronger in men than in women.

SUBMITTER: Mellinger JL

PROVIDER: S-EPMC5282653 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Hepatic steatosis and cardiovascular disease outcomes: An analysis of the Framingham Heart Study.

Mellinger Jessica L JL Pencina Karol M KM Massaro Joseph M JM Hoffmann Udo U Seshadri Sudha S Fox Caroline S CS O'Donnell Christopher J CJ Speliotes Elizabeth K EK

Journal of hepatology 20150314 2

<h4>Background & aims</h4>Non-alcoholic fatty liver disease (NAFLD) is highly prevalent and is associated with development of metabolic disease including atherosclerotic cardiovascular disease (CVD). Our aim is to examine the association of hepatic steatosis with prevalent clinical and subclinical CVD outcomes in a large community-based sample, the Framingham Heart Study.<h4>Methods</h4>Hepatic steatosis was measured in 3529 participants using multidetector computed tomography scanning. Multivar ...[more]

PMID: 25776891

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Project description:BACKGROUND:Cardiovascular disease (CVD) and its most common manifestations--including coronary heart disease (CHD), stroke, heart failure (HF), and atrial fibrillation (AF)--are major causes of morbidity and mortality. In many industrialized countries, cardiovascular disease (CVD) claims more lives each year than any other disease. Heart disease and stroke are the first and third leading causes of death in the United States. Prior investigations have reported several single gene variants associated with CHD, stroke, HF, and AF. We report a community-based genome-wide association study of major CVD outcomes. METHODS:In 1345 Framingham Heart Study participants from the largest 310 pedigrees (54% women, mean age 33 years at entry), we analyzed associations of 70,987 qualifying SNPs (Affymetrix 100K GeneChip) to four major CVD outcomes: major atherosclerotic CVD (n = 142; myocardial infarction, stroke, CHD death), major CHD (n = 118; myocardial infarction, CHD death), AF (n = 151), and HF (n = 73). Participants free of the condition at entry were included in proportional hazards models. We analyzed model-based deviance residuals using generalized estimating equations to test associations between SNP genotypes and traits in additive genetic models restricted to autosomal SNPs with minor allele frequency > or =0.10, genotype call rate > or =0.80, and Hardy-Weinberg equilibrium p-value > or = 0.001. RESULTS:Six associations yielded p < 10(-5). The lowest p-values for each CVD trait were as follows: major CVD, rs499818, p = 6.6 x 10(-6); major CHD, rs2549513, p = 9.7 x 10(-6); AF, rs958546, p = 4.8 x 10(-6); HF: rs740363, p = 8.8 x 10(-6). Of note, we found associations of a 13 Kb region on chromosome 9p21 with major CVD (p 1.7-1.9 x 10(-5)) and major CHD (p 2.5-3.5 x 10(-4)) that confirm associations with CHD in two recently reported genome-wide association studies. Also, rs10501920 in CNTN5 was associated with AF (p = 9.4 x 10(-6)) and HF (p = 1.2 x 10(-4)). Complete results for these phenotypes can be found at the dbgap website http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007 webcite. CONCLUSION:No association attained genome-wide significance, but several intriguing findings emerged. Notably, we replicated associations of chromosome 9p21 with major CVD. Additional studies are needed to validate these results. Finding genetic variants associated with CVD may point to novel disease pathways and identify potential targeted preventive therapies.

Project description:Background and purposeNovel noninvasive measures of vascular function are emerging as subclinical markers for cardiovascular disease (CVD) and may be useful to predict CVD events. The purpose of our prospective study was to assess associations between digital peripheral arterial tonometry (PAT) measures and first-onset major CVD events in a sample of FHS (Framingham Heart Study) participants.MethodsUsing a fingertip PAT device, we assessed pulse amplitude in Framingham Offspring and Third Generation participants (n=3865; mean age, 55±14 years; 52% women) at baseline and in 30-second intervals for 4 minutes during reactive hyperemia. The PAT ratio (relative hyperemia index) was calculated as the post-to-pre occlusion pulse signal ratio in the occluded arm, relative to the same ratio in the control (nonoccluded) arm, and corrected for baseline vascular tone. Baseline pulse amplitude and PAT ratio during hyperemia are measures of pressure pulsatility and microvascular function in the finger, respectively. We used Cox proportional hazards regression to relate PAT measures in the fingertip to incident CVD events.ResultsDuring follow-up (median, 9.2 years; range, 0.04–10.0 years), 270 participants (7%) experienced new-onset CVD events (n=270). In multivariable models adjusted for cardiovascular risk factors, baseline pulse amplitude (hazard ratio [HR] per 1 SD, 1.04 [95% CI, 0.90–1.21]; P=0.57) and PAT ratio (HR, 0.95 [95% CI, 0.84–1.08]; P=0.43) were not significantly related to incident composite CVD events, including myocardial infarction or heart failure. However, higher PAT ratio (HR, 0.76 [95% CI, 0.61–0.94]; P=0.013), but not baseline pulse amplitude (HR, 1.15 [95% CI, 0.89–1.49]; P=0.29), was related to lower risk for incident stroke. In a sensitivity analysis by stroke subtype, higher PAT ratio was related to lower risk of incident ischemic stroke events (HR, 0.68 [95% CI, 0.53–0.86]; P=0.001).ConclusionsNovel digital PAT measures may represent a marker of stroke risk in the community.

Project description:Background Data are limited on the association of mildly reduced estimated glomerular filtration rate (eGFR 60-89 mL/min per 1.73 m2) with cardiovascular disease (CVD) in the community. Methods and Results We evaluated 3066 Framingham Offspring Study participants (55% women, mean age 58 years), without clinical CVD. Using multivariable regression, we related categories of mildly reduced eGFR (80-89, 70-79, or 60-69 versus ≥90 mL/min per 1.73 m2 [referent]) to prevalent coronary artery calcium, carotid intima media thickness, and left ventricular hypertrophy, and to circulating concentrations of cardiac stress biomarkers. We related eGFR categories to CVD incidence and to progression to ≥Stage 3 chronic kidney disease (eGFR <60 mL/min per 1.73 m2) using Cox regression. Individuals with eGFR 60-69 mL/min per 1.73 m2 (n=320) had higher coronary artery calcium score (odds ratio 1.69; 95% CI 1.02-2.80) compared with the referent group. Individuals with eGFR 60-69 and 70-79 mL/min per 1.73 m2 had higher blood growth differentiating factor-15 concentrations (β=0.131 and 0.058 per unit-increase in log-biomarker, respectively). Participants with eGFR 60-69 and 80-89 mL/min per 1.73 m2 had higher blood B-type natriuretic peptide concentrations (β=0.119 and 0.116, respectively). On follow-up (median 16 years; 691 incident CVD and 252 chronic kidney disease events), individuals with eGFR 60-69 and 70-79 mL/min per 1.73 m2 experienced higher CVD incidence (hazard ratio [HR], 1.40; 95% CI, 1.02-1.93 and 1.45, 95% CI, 1.05-2.00, respectively, versus referent). Participants with eGFR 60-69 mL/min per 1.73 m2 experienced higher chronic kidney disease incidence (HR, 2.94; 95% CI, 1.80-4.78 versus referent). Conclusions Individuals with mildly reduced eGFR 60-69 mL/min per 1.73 m2 have a higher burden of subclinical atherosclerosis cross-sectionally, and a greater risk of CVD and chronic kidney disease progression prospectively. Additional studies are warranted to confirm our findings.

Dataset Information

Hepatic steatosis and cardiovascular disease outcomes: An analysis of the Framingham Heart Study.

Publications

Hepatic steatosis and cardiovascular disease outcomes: An analysis of the Framingham Heart Study.

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