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Hyperlipidemia in early adulthood increases long-term risk of coronary heart disease.

ABSTRACT: BACKGROUND:Many young adults with moderate hyperlipidemia do not meet statin treatment criteria under the new American Heart Association/American College of Cardiology cholesterol guidelines because they focus on 10-year cardiovascular risk. We evaluated the association between years of exposure to hypercholesterolemia in early adulthood and future coronary heart disease (CHD) risk. METHODS AND RESULTS:We examined Framingham Offspring Cohort data to identify adults without incident cardiovascular disease to 55 years of age (n=1478), and explored the association between duration of moderate hyperlipidemia (non-high-density lipoprotein cholesterol ? 160 mg/dL) in early adulthood and subsequent CHD. At median 15-year follow-up, CHD rates were significantly elevated among adults with prolonged hyperlipidemia exposure by 55 years of age: 4.4% for those with no exposure, 8.1% for those with 1 to 10 years of exposure, and 16.5% for those with 11 to 20 years of exposure (P<0.001); this association persisted after adjustment for other cardiac risk factors including non-high-density lipoprotein cholesterol at 55 years of age (hazard ratio, 1.39; 95% confidence interval, 1.05-1.85 per decade of hyperlipidemia). Overall, 85% of young adults with prolonged hyperlipidemia would not have been recommended for statin therapy at 40 years of age under current national guidelines. However, among those not considered statin therapy candidates at 55 years of age, there remained a significant association between cumulative exposure to hyperlipidemia in young adulthood and subsequent CHD risk (adjusted hazard ratio, 1.67; 95% confidence interval, 1.06-2.64). CONCLUSIONS:Cumulative exposure to hyperlipidemia in young adulthood increases the subsequent risk of CHD in a dose-dependent fashion. Adults with prolonged exposure to even moderate elevations in non-high-density lipoprotein cholesterol have elevated risk for future CHD and may benefit from more aggressive primary prevention.

SUBMITTER: Navar-Boggan AM

PROVIDER: S-EPMC4370230 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Hyperlipidemia in early adulthood increases long-term risk of coronary heart disease.

Navar-Boggan Ann Marie AM Peterson Eric D ED D'Agostino Ralph B RB Neely Benjamin B Sniderman Allan D AD Pencina Michael J MJ

Circulation 20150126 5

<h4>Background</h4>Many young adults with moderate hyperlipidemia do not meet statin treatment criteria under the new American Heart Association/American College of Cardiology cholesterol guidelines because they focus on 10-year cardiovascular risk. We evaluated the association between years of exposure to hypercholesterolemia in early adulthood and future coronary heart disease (CHD) risk.<h4>Methods and results</h4>We examined Framingham Offspring Cohort data to identify adults without inciden ...[more]

PMID: 25623155

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Project description:BackgroundAtherosclerosis is a multifactorial disorder of the heart vessels that develops over decades, coupling inflammatory mechanisms and elevated total cholesterol levels under the influence of genetic and environmental factors. Without effective intervention, atherosclerosis consequently causes coronary heart disease (CHD), which leads to increased risk of sudden death. Polymorphonuclear neutrophils play a pivotal role in inflammation and atherogenesis. Human neutrophil peptides (HNPs) or alpha (α)-defensins are cysteine-rich cation polypeptides that are produced and released from activated polymorphonuclear neutrophil granules during septic inflammation and acute coronary vascular disorders. HNPs cause endothelial cell dysfunction during early atherogenesis. In this cross-sectional study, control, hyperlipidemia and CHD groups were representative as atherosclerosis development and CHD complications. We aimed to assess the correlation between α-defensin expression and the development of CHD, and whether it was a useful predictive indicator for CHD risk.MethodsFirst, DNA microarray analysis was performed on peripheral blood mononuclear cells (PBMCs) from Thai control, hyperlipidemia and CHD male patients (n = 7). Gene expression profiling revealed eight up-regulated genes common between hyperlipidemia and CHD patients, but not controls. We sought to verify and compare α-defensin expression among the groups using: 1) real-time quantitative RT-PCR (qRT-PCR) to determine α-defensin mRNA expression (n = 10), and 2) enzyme-linked immunosorbent assay to determine plasma HNP 1-3 levels (n = 17). Statistically significant differences and correlations between groups were determined by the Mann-Whitney U test or the Kruskal-Wallis test, and the Rho-Spearman correlation, respectively.ResultsWe found that α-defensin mRNA expression increased (mean 2-fold change) in the hyperlipidemia (p = 0.043) and CHD patients (p = 0.05) compared with the controls. CHD development moderately correlated with α-defensin mRNA expression (r = 0.429, p = 0.023) and with plasma HNP 1-3 levels (r = 0.486, p = 0.000).ConclusionsIncreased α-defensin expression is a potential inflammatory marker that may predict the risk of CHD development in Thai hyperlipidemia patients.

Project description:Objective To examine the association of long term intake of gluten with the development of incident coronary heart disease.Design Prospective cohort study.Setting and participants 64 714 women in the Nurses' Health Study and 45 303 men in the Health Professionals Follow-up Study without a history of coronary heart disease who completed a 131 item semiquantitative food frequency questionnaire in 1986 that was updated every four years through 2010.Exposure Consumption of gluten, estimated from food frequency questionnaires.Main outcome measure Development of coronary heart disease (fatal or non-fatal myocardial infarction).Results During 26 years of follow-up encompassing 2 273 931 person years, 2431 women and 4098 men developed coronary heart disease. Compared with participants in the lowest fifth of gluten intake, who had a coronary heart disease incidence rate of 352 per 100 000 person years, those in the highest fifth had a rate of 277 events per 100 000 person years, leading to an unadjusted rate difference of 75 (95% confidence interval 51 to 98) fewer cases of coronary heart disease per 100 000 person years. After adjustment for known risk factors, participants in the highest fifth of estimated gluten intake had a multivariable hazard ratio for coronary heart disease of 0.95 (95% confidence interval 0.88 to 1.02; P for trend=0.29). After additional adjustment for intake of whole grains (leaving the remaining variance of gluten corresponding to refined grains), the multivariate hazard ratio was 1.00 (0.92 to 1.09; P for trend=0.77). In contrast, after additional adjustment for intake of refined grains (leaving the variance of gluten intake correlating with whole grain intake), estimated gluten consumption was associated with a lower risk of coronary heart disease (multivariate hazard ratio 0.85, 0.77 to 0.93; P for trend=0.002).Conclusion Long term dietary intake of gluten was not associated with risk of coronary heart disease. However, the avoidance of gluten may result in reduced consumption of beneficial whole grains, which may affect cardiovascular risk. The promotion of gluten-free diets among people without celiac disease should not be encouraged.

Project description:BackgroundUnderstanding the predictive utility of previously derived polygenic risk scores (PRSs) for long-term risk of coronary heart disease (CHD) and its additive value beyond traditional risk factors can inform prevention strategies.MethodsData from adults 20 to 59 years of age who were free of CHD from the FOS (Framingham Offspring Study) and the ARIC (Atherosclerosis Risk in Communities) study were analyzed. Because the PRS was derived from samples of predominantly European ancestry, individuals who self-reported White race were included. The sample was stratified by age and cohort: young (FOS, 20-39 years [median, 30 years] of age), early midlife (FOS, 40-59 years [median, 43] years of age), and late midlife (ARIC, 45-59 years [median, 52 years] of age). Two previously derived and validated prediction tools were applied: (1) a 30-year traditional risk factor score and (2) a genome-wide PRS comprising >6 million genetic variants. Hazard ratios for the association between each risk estimate and incident CHD were calculated. Predicted and observed rates of CHD were compared to assess discrimination for each model individually and together with the optimism-corrected C index (95% CI).ResultsAmong 9757 participants, both the traditional risk factor score (hazard ratio per 1 SD, 2.60 [95% CI, 2.08-3.27], 2.09 [95% CI, 1.83-2.40], and 2.11 [95% CI, 1.96-2.28]) and the PRS (hazard ratio, 1.98 [95% CI, 1.70-2.30], 1.64 [95% CI, 1.47-1.84], and 1.22 [95% CI, 1.15-1.30]) were significantly associated with incident CHD in young, early midlife, and late midlife, respectively. Discrimination was similar or better for the traditional risk factor score (C index, 0.74 [95% CI, 0.70-0.78], 0.70 [95% CI, 0.67-0.72], and 0.72 [95% CI, 0.70-0.73]) compared with an age- and sex-adjusted PRS (0.73 [95% CI, 0.69-0.78], 0.66 [95% CI, 0.62-0.69], and 0.66 [95% CI, 0.64-0.67]) in young, early-midlife, and late-midlife participants, respectively. The ΔC index when PRS was added to the traditional risk factor score was 0.03 (95% CI, 0.001-0.05), 0.02 (95% CI, -0.002 to 0.037), and 0.002 (95% CI, -0.002 to 0.006) in young, early-midlife, and late-midlife participants, respectively.ConclusionsDespite a statistically significant association between PRS and 30-year risk of CHD, the C statistic improved only marginally with the addition of PRS to the traditional risk factor model among young adults and did not improve among midlife adults. PRS, an immutable factor that cannot be directly intervened on, has minimal clinical utility for long-term CHD prediction when added to a traditional risk factor model.

Dataset Information

Hyperlipidemia in early adulthood increases long-term risk of coronary heart disease.

Publications

Hyperlipidemia in early adulthood increases long-term risk of coronary heart disease.

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