Dataset Information

APOE and the Association of Fatty Acids With the Risk of Stroke, Coronary Heart Disease, and Mortality.

ABSTRACT: Background and Purpose- The role of dietary fat on cardiovascular health and mortality remains under debate. Because the APOE is central to the transport and metabolism of lipids, we examined associations between plasma fatty acids and the risk of stroke, coronary heart disease, and mortality by APOE-?4 genotype. Methods- We included 943 FHS (Framingham Heart Study) and 1406 3C (Three-City) Bordeaux Study participants. Plasma docosahexaenoic, linoleic, arachidonic, and palmitic fatty acids were measured at baseline by gas chromatography. All-cause stroke, ischemic stroke, coronary heart disease, and all-cause mortality events were identified prospectively using standardized protocols. Each cohort used Cox models to separately relate fatty acid levels to the risk of developing each event during ?10 years of follow-up adjusting for potential confounders and stratifying by APOE genotype (?4 carriers versus noncarriers). We then meta-analyzed summary statistics using random-effects models. Results- On average, participants had a mean age of 74 years, 61% were women, and 21% (n=483) were APOE-?4 carriers. Meta-analysis results showed that, only among APOE-?4 carriers, every SD unit increase in linoleic acid was associated with a reduced risk of all-cause stroke (hazard ratio [HR], 0.54 [95% CI, 0.38-0.78]), ischemic stroke (HR, 0.48 [95% CI, 0.33-0.71]), and all-cause mortality (HR, 0.70 [95% CI, 0.57-0.85]). In contrast, every SD unit increase in palmitic acid was related to an increased risk of all-cause stroke (HR, 1.58 [95% CI, 1.16-2.17]), ischemic stroke (HR, 1.76 [95% CI, 1.26-2.45]), and coronary heart disease (HR, 1.48 [95% CI, 1.09-2.01]), also in APOE-?4 carriers only. Results for docosahexaenoic acid and arachidonic acid were heterogeneous between cohorts. Conclusions- These exploratory results suggest that APOE-?4 carriers may be more susceptible to the beneficial or adverse impact of fatty acids on cardiovascular disease and mortality. In this subgroup, higher linoleic acid was protective for stroke and mortality, whereas palmitic acid was a risk factor for stroke and coronary heart disease. The mechanisms underlying these novel findings warrant further investigation.

SUBMITTER: Satizabal CL

PROVIDER: S-EPMC6310220 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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APOE and the Association of Fatty Acids With the Risk of Stroke, Coronary Heart Disease, and Mortality.

Satizabal Claudia L CL Samieri Cécilia C Davis-Plourde Kendra L KL Voetsch Barbara B Aparicio Hugo J HJ Pase Matthew P MP Romero José Rafael JR Helmer Catherine C Vasan Ramachandran S RS Kase Carlos S CS Debette Stéphanie S Beiser Alexa S AS Seshadri Sudha S

Stroke 20181201 12

Background and Purpose- The role of dietary fat on cardiovascular health and mortality remains under debate. Because the APOE is central to the transport and metabolism of lipids, we examined associations between plasma fatty acids and the risk of stroke, coronary heart disease, and mortality by APOE-ε4 genotype. Methods- We included 943 FHS (Framingham Heart Study) and 1406 3C (Three-City) Bordeaux Study participants. Plasma docosahexaenoic, linoleic, arachidonic, and palmitic fatty acids were ...[more]

PMID: 30571417

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Project description:BACKGROUND:Intraindividual blood pressure (BP) fluctuates dynamically over time. Previous studies suggested an adverse link between greater visit-to-visit variability in systolic blood pressure (SBP) and various outcomes. However, these studies have significant limitations, such as a small size, inclusion of selected populations, and restricted outcomes. OBJECTIVES:This study investigated the association of increased visit-to-visit variability and all-cause mortality, cardiovascular events, and end-stage renal disease (ESRD) in a large cohort of U.S. veterans. METHODS:From among 3,285,684 U.S. veterans with and without hypertension and normal estimated glomerular filtration rates (eGFR) during 2005 and 2006, we identified 2,865,157 patients who had 8 or more outpatient BP measurements. Systolic blood pressure variability (SBPV) was measured using the SD of all SBP values (normally distributed) in 1 individual. Associations of SD quartiles (<10.3, 10.3 to 12.7, 12.7 to 15.6, and ?15.6 mm Hg) with all-cause mortality, incident coronary heart disease (CHD), stroke, and ESRD was examined using Cox models adjusted for sociodemographic characteristics, baseline eGFR, comorbidities, body mass index, SBP, diastolic BP, and antihypertensive medication use. RESULTS:Several sociodemographic variables (older age, male sex, African-American race, divorced or widowed status) and clinical characteristics (lower baseline eGFR, higher SBP and diastolic BP), and comorbidities (presence of diabetes, hypertension, cardiovascular disease, and lung disease) were all associated with higher intraindividual SBPV. The multivariable adjusted hazard ratios and 95% confidence intervals for SD quartiles 2 through 4 (compared with the first quartile) associated with all-cause mortality, CHD, stroke, and ESRD were incrementally higher. CONCLUSIONS:Higher SBPV in individuals with and without hypertension was associated with increased risks of all-cause mortality, CHD, stroke, and ESRD. Further studies are needed to determine interventions that can lower SBPV and their impact on adverse health outcomes.

Project description:Background We aimed at investigating the association of circulating fatty acids with coronary heart disease (CHD) and stroke risk. Methods and Results We conducted an individual-participant data meta-analysis of 5 UK-based cohorts and 1 matched case-control study. Fatty acids (ie, omega-3 docosahexaenoic acid, omega-6 linoleic acid, monounsaturated and saturated fatty acids) were measured at baseline using an automated high-throughput serum nuclear magnetic resonance metabolomics platform. Data from 3022 incident CHD cases (13 104 controls) and 1606 incident stroke cases (13 369 controls) were included. Logistic regression was used to model the relation between fatty acids and odds of CHD and stroke, adjusting for demographic and lifestyle variables only (ie, minimally adjusted model) or with further adjustment for other fatty acids (ie, fully adjusted model). Although circulating docosahexaenoic acid, but not linoleic acid, was related to lower CHD risk in the fully adjusted model (odds ratio, 0.85; 95% CI, 0.76-0.95 per standard unit of docosahexaenoic acid), there was evidence of high between-study heterogeneity and effect modification by study design. Stroke risk was consistently lower with increasing circulating linoleic acid (odds ratio for fully adjusted model, 0.82; 95% CI, 0.75-0.90). Circulating monounsaturated fatty acids were associated with higher CHD risk across all models and with stroke risk in the fully adjusted model (odds ratio, 1.22; 95% CI, 1.03-1.44). Saturated fatty acids were not related to increased CHD risk in the fully adjusted model (odds ratio, 0.94; 95% CI, 0.82-1.09), or stroke risk. Conclusions We found consistent evidence that linoleic acid was associated with decreased risk of stroke and that monounsaturated fatty acids were associated with increased risk of CHD. The different pattern between CHD and stroke in terms of fatty acids risk profile suggests future studies should be cautious about using composite events. Different study designs are needed to assess which, if any, of the associations observed is causal.

Project description:CONTEXT:Circulating concentration of lipoprotein(a) (Lp[a]), a large glycoprotein attached to a low-density lipoprotein-like particle, may be associated with risk of coronary heart disease (CHD) and stroke. OBJECTIVE:To assess the relationship of Lp(a) concentration with risk of major vascular and nonvascular outcomes. STUDY SELECTION:Long-term prospective studies that recorded Lp(a) concentration and subsequent major vascular morbidity and/or cause-specific mortality published between January 1970 and March 2009 were identified through electronic searches of MEDLINE and other databases, manual searches of reference lists, and discussion with collaborators. DATA EXTRACTION:Individual records were provided for each of 126,634 participants in 36 prospective studies. During 1.3 million person-years of follow-up, 22,076 first-ever fatal or nonfatal vascular disease outcomes or nonvascular deaths were recorded, including 9336 CHD outcomes, 1903 ischemic strokes, 338 hemorrhagic strokes, 751 unclassified strokes, 1091 other vascular deaths, 8114 nonvascular deaths, and 242 deaths of unknown cause. Within-study regression analyses were adjusted for within-person variation and combined using meta-analysis. Analyses excluded participants with known preexisting CHD or stroke at baseline. DATA SYNTHESIS:Lipoprotein(a) concentration was weakly correlated with several conventional vascular risk factors and it was highly consistent within individuals over several years. Associations of Lp(a) with CHD risk were broadly continuous in shape. In the 24 cohort studies, the rates of CHD in the top and bottom thirds of baseline Lp(a) distributions, respectively, were 5.6 (95% confidence interval [CI], 5.4-5.9) per 1000 person-years and 4.4 (95% CI, 4.2-4.6) per 1000 person-years. The risk ratio for CHD, adjusted for age and sex only, was 1.16 (95% CI, 1.11-1.22) per 3.5-fold higher usual Lp(a) concentration (ie, per 1 SD), and it was 1.13 (95% CI, 1.09-1.18) following further adjustment for lipids and other conventional risk factors. The corresponding adjusted risk ratios were 1.10 (95% CI, 1.02-1.18) for ischemic stroke, 1.01 (95% CI, 0.98-1.05) for the aggregate of nonvascular mortality, 1.00 (95% CI, 0.97-1.04) for cancer deaths, and 1.00 (95% CI, 0.95-1.06) for nonvascular deaths other than cancer. CONCLUSION:Under a wide range of circumstances, there are continuous, independent, and modest associations of Lp(a) concentration with risk of CHD and stroke that appear exclusive to vascular outcomes.

Project description:AimTo analyze the risk of coronary heart disease in patients with type 2 diabetes mellitus (T2DM) receiving standard medical treatment.MethodsWe performed a retrospective chart analysis of 269 middle-aged patients (age 45-64 years, mean age, 53.9 ± 5.5 years) with T2DM and without atherosclerotic cardiovascular events who underwent typing to determine their apolipoprotein E (apoE) isoforms. The apoE isoforms were determined using isoelectric focusing, followed by immunoblotting. We retrospectively evaluated the charts of the 269 patients, recorded between their first visit to the hospital (the study's start point, between 1987 and 1992) and the occurrence of an atherosclerotic cardiovascular event (the study's endpoint) or January 2004, whichever came first. The age-adjusted mean values and the prevalences of covariates were calculated to compare the laboratory data among the apoE phenotypes. To investigate the association of risk factors with the incidence of coronary heart disease during the follow-up period, monovariate and multivariate Cox regression models were used.ResultsAt enrollment, the mean serum low density lipoprotein (LDL) cholesterol levels were lowest (2.92 ± 0.89 mmol/L) among the subjects with apoE2 (apoE2/2 or apoE2/3) and highest (3.52 ± 0.77 mmol/L) among the subjects with apoE4 (apoE3/4 or apoE4/4). No significant differences in mean age or the percentage of smokers were observed among the three groups. Furthermore, no significant differences were observed in the systolic and diastolic blood pressures, body mass index, HbA1c level or serum triglyceride levels among the three groups. There were 47 cases of coronary heart disease over 3285 person-years of follow-up. An age-adjusted multivariate Cox proportional model identified diabetic retinopathy (hazard ratio, 2.38, 95% CI: 1.28-4.43, P = 0.006), a high systolic blood pressure (hazard ratio, 1.04, 95% CI: 1.02-1.06, P < 0.001) and high HbA1c values (hazard ratio, 1.19, 95% CI: 1.02-1.38, P = 0.0029), but not the LDL cholesterol value at enrollment (hazard ratio, 1.01, 95% CI: 0.97-1.05, P = 0.77) nor the specific apoE isoform, as significant predictors of coronary heart disease.ConclusionUnder standard medical treatment of diabetes, including the control of LDL cholesterol levels, the apoE4 isoform was not associated with coronary heart disease among T2DM patients.

Project description:BACKGROUND: The relationship between dietary glycemic index, glycemic load and risk of coronary heart disease (CHD), stroke, and stroke-related mortality is inconsistent. METHODS: We systematically searched the MEDLINE, EMBASE, and Science Citation Index Expanded databases using glycemic index, glycemic load, and cardiovascular disease and reference lists of retrieved articles up to April 30, 2012. We included prospective studies with glycemic index and glycemic load as the exposure and incidence of fatal and nonfatal CHD, stroke, and stroke-related mortality as the outcome variable. Pooled relative risks (RR) and 95% confidence intervals (CI) were calculated using random-effects models. RESULTS: Fifteen prospective studies with a total of 438,073 participants and 9,424 CHD cases, 2,123 stroke cases, and 342 deaths from stroke were included in the meta-analysis. Gender significantly modified the effects of glycemic index and glycemic load on CHD risk, and high glycemic load level was associated with higher risk of CHD in women (RR=1.49, 95%CI 1.27-1.73), but not in men (RR=1.08, 95%CI 0.91-1.27). Stratified meta-analysis by body mass index indicated that among overweight and obese subjects, dietary glycemic load level were associated with increased risk of CHD (RR=1.49, 95%CI 1.27-1.76; P for interaction=0.003). Higher dietary glycemic load, but not glycemic index, was positively associated with stroke (RR=1.19, 95% CI 1.00-1.43). There is a linear dose-response relationship between dietary glycemic load and increased risk of CHD, with pooled RR of 1.05 (95%CI 1.02-1.08) per 50-unit increment in glycemic load level. CONCLUSION: High dietary glycemic load is associated with a higher risk of CHD and stroke, and there is a linear dose-response relationship between glycemic load and CHD risk. Dietary glycemic index is slightly associated with risk of CHD, but not with stroke and stroke-related death. Further studies are needed to verify the effects of gender and body weight on cardiovascular diseases.

Project description:We investigated the association of dietary intake of major types of fatty acids with heart disease mortality in a general adult cohort with or without a prior diagnosis of myocardial infarction (MI). This cohort study included US adults who attended the National Health and Nutrition Examination Surveys from 1988 to 2014. Heart disease mortality was ascertained by linkage to the National Death Index records through 31 December 2015. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of fatty acid intake for heart disease mortality. This cohort included 45,820 adults among which 1,541 had a prior diagnosis of MI. Participants were followed up for 532,722 person-years (mean follow-up, 11.6 years), with 2,313 deaths recorded from heart disease being recorded. Intake of saturated (SFAs) and monounsaturated fatty acids (MUFAs) was associated with heart disease mortality after adjustment for all the tested confounders. In contrast, a 5% higher calorie intake from polyunsaturated fatty acids (PUFAs) was associated with a 9% (HR, 0.91; 95% CI 0.83–1.00; P = 0.048) lower multivariate-adjusted risk of heart disease mortality. Sub-analyses showed that this inverse association was present in those without a prior diagnosis of MI (HR,0.89; 95% CI 0.80–0.99) but not in those with the condition (HR, 0.94; 95% CI 0.75–1.16). The lack of association in the MI group could be due to a small sample size or severity and procedural complications (e.g., stenting and medication adherence) of the disease. Higher PUFA intake was associated with a favourable lipid profile. However, further adjustment for plasma lipids did not materially change the inverse association between PUFAs and heart disease mortality. Higher intake of PUFAs, but not SFAs and MUFAs, was associated with a lower adjusted risk of heart disease mortality in a large population of US adults supporting the need to increase dietary PUFA intake in the general public.

Dataset Information

APOE and the Association of Fatty Acids With the Risk of Stroke, Coronary Heart Disease, and Mortality.

Publications

APOE and the Association of Fatty Acids With the Risk of Stroke, Coronary Heart Disease, and Mortality.

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