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Fatty liver predicts the risk for cardiovascular events in middle-aged population: a population-based cohort study.

ABSTRACT: We investigated if the differences in liver fat content would predict the development of non-fatal and fatal atherosclerotic endpoints (coronary heart disease and stroke).Our study group is a population-based, randomly recruited cohort (Oulu Project Elucidating Risk of Atherosclerosis, OPERA), initiated in 1991. The cohort consisted of 988 middle-aged Finnish participants.Total mortality and hospital events were followed up to 2009 based on the registry of the National Institute for Health and Welfare and the National death registry.The severity of hepatic steatosis was measured by ultrasound and divided into three groups (0-2). Cox regression analysis was used in the statistical analysis.In the follow-up of years 1991-2009, 13.5% of the participants with non-fatty liver, 24.2% of participants having moderate liver fat content and 29.2% of the participants having severe fatty liver experienced a cardiovascular event during the follow-up time (p<0.001). Severe liver fat content predicted the risk for future risk of cardiovascular event even when adjusted for age, gender and study group (HR 1.92, CI 1.32 to 2.80, p<0.01). When further adjustments for smoking, alcohol consumption, low-density lipoprotein-cholesterol, body mass index and systolic blood pressure were conducted, the risk still remained statistically significant (HR 1.74, CI 1.16 to 2.63, p<0.01). Statistical significance disappeared with further adjustment for QUICKI.Liver fat content increases the risk of future cardiovascular disease event in long-term follow-up but it is seems to be dependent on insulin sensitivity.

SUBMITTER: Pisto P

PROVIDER: S-EPMC3963104 | biostudies-other | 2014

REPOSITORIES: biostudies-other

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Fatty liver predicts the risk for cardiovascular events in middle-aged population: a population-based cohort study.

Pisto Pauliina P Santaniemi Merja M Bloigu Risto R Ukkola Olavi O Kesäniemi Y Antero YA

BMJ open 20140320 3

<h4>Objective</h4>We investigated if the differences in liver fat content would predict the development of non-fatal and fatal atherosclerotic endpoints (coronary heart disease and stroke).<h4>Design, setting and participants</h4>Our study group is a population-based, randomly recruited cohort (Oulu Project Elucidating Risk of Atherosclerosis, OPERA), initiated in 1991. The cohort consisted of 988 middle-aged Finnish participants.<h4>Intervention</h4>Total mortality and hospital events were foll ...[more]

PMID: 24650811

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Project description:More than 1.5 million US adults use stimulants and other medications labeled for treatment of attention-deficit/hyperactivity disorder (ADHD). These agents can increase heart rate and blood pressure, raising concerns about their cardiovascular safety.To examine whether current use of medications prescribed primarily to treat ADHD is associated with increased risk of serious cardiovascular events in young and middle-aged adults.Retrospective, population-based cohort study using electronic health care records from 4 study sites (OptumInsight Epidemiology, Tennessee Medicaid, Kaiser Permanente California, and the HMO Research Network), starting in 1986 at 1 site and ending in 2005 at all sites, with additional covariate assessment using 2007 survey data. Participants were adults aged 25 through 64 years with dispensed prescriptions for methylphenidate, amphetamine, or atomoxetine at baseline. Each medication user (n = 150,359) was matched to 2 nonusers on study site, birth year, sex, and calendar year (443,198 total users and nonusers).Serious cardiovascular events, including myocardial infarction (MI), sudden cardiac death (SCD), or stroke, with comparison between current or new users and remote users to account for potential healthy-user bias.During 806,182 person-years of follow-up (median, 1.3 years per person), 1357 cases of MI, 296 cases of SCD, and 575 cases of stroke occurred. There were 107,322 person-years of current use (median, 0.33 years), with a crude incidence per 1000 person-years of 1.34 (95% CI, 1.14-1.57) for MI, 0.30 (95% CI, 0.20-0.42) for SCD, and 0.56 (95% CI, 0.43-0.72) for stroke. The multivariable-adjusted rate ratio (RR) of serious cardiovascular events for current use vs nonuse of ADHD medications was 0.83 (95% CI, 0.72-0.96). Among new users of ADHD medications, the adjusted RR was 0.77 (95% CI, 0.63-0.94). The adjusted RR for current use vs remote use was 1.03 (95% CI, 0.86-1.24); for new use vs remote use, the adjusted RR was 1.02 (95% CI, 0.82-1.28); the upper limit of 1.28 corresponds to an additional 0.19 events per 1000 person-years at ages 25-44 years and 0.77 events per 1000 person-years at ages 45-64 years.Among young and middle-aged adults, current or new use of ADHD medications, compared with nonuse or remote use, was not associated with an increased risk of serious cardiovascular events. Apparent protective associations likely represent healthy-user bias.

Project description:Background FGF21 (fibroblast growth factor 21), a novel hepatokine regulating lipid metabolism, has been linked to atherosclerotic disease. However, whether this relationship exists in patients without nonalcoholic fatty liver disease is unclear. We assessed the association between serum FGF21 levels and atherosclerosis in patients without nonalcoholic fatty liver disease, and investigated whether baseline FGF21 could predict incident atherosclerotic cardiovascular disease in a 7-year prospective cohort. Methods and Results Baseline serum FGF21 was measured in a cross-sectional cohort of 371 patients with type 2 diabetes mellitus without nonalcoholic fatty liver disease (determined by hepatic magnetic resonance spectroscopy), and in a population-based prospective cohort of 705 patients from the Shanghai Diabetes Study. In the cross-sectional study, FGF21 was significantly higher in patients with than in those without subclinical carotid atherosclerosis (P<0.01). The association remained significant after adjusting for demographic and traditional cardiovascular risk factors. In the prospective cohort, 80 patients developed atherosclerotic cardiovascular disease during follow-up. Baseline FGF21 was significantly higher in those who developed ischemic heart disease or cerebral infarction than in those who did not. Using a cutoff serum concentration of 232.0 pg/mL, elevated baseline FGF21 independently predicted incident total atherosclerotic cardiovascular disease events, ischemic heart disease, and cerebral infarction in a nondiabetic population (all P<0.05), and significantly improved the discriminatory and reclassifying abilities of our prediction model after adjustment for established cardiovascular risk factors. Conclusions This study provides the first evidence that FGF21 levels are elevated in patients without nonalcoholic fatty liver disease with subclinical atherosclerosis. Baseline FGF21 is an independent predictor of atherosclerotic cardiovascular disease and represents a novel biomarker for primary prevention in the general population.

Dataset Information

Fatty liver predicts the risk for cardiovascular events in middle-aged population: a population-based cohort study.

Publications

Fatty liver predicts the risk for cardiovascular events in middle-aged population: a population-based cohort study.

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