Dataset Information

ADP Platelet Hyperreactivity Predicts Cardiovascular Disease in the FHS (Framingham Heart Study).

ABSTRACT: BACKGROUND:Platelet function is associated with adverse events in patients with cardiovascular disease (CVD). METHODS AND RESULTS:We examined associations of baseline platelet function with incident CVD events in the community-based FHS (Framingham Heart Study). Participants free of prevalent CVD and without recent aspirin treatment with available data in the Framingham Offspring cohort (1991-1995) and Omni cohort (1994-1998) were included. Platelet function was measured with light transmission aggregometry using collagen (1.9 ?g/mL), ADP (0.05-15 ?mol/L), and epinephrine (0.01-15 ?mol/L). We used proportional hazards models to analyze incident outcomes (myocardial infarction/stroke, CVD, and CVD mortality) with respect to platelet measures. The study sample included 2831 participants (average age, 54.3 years; 57% women). During follow-up (median, 20.4 years), we observed 191 composite incident myocardial infarction or stroke events, 432 incident CVD cases, and 117 CVD deaths. Hyperreactivity to ADP and platelet aggregation at ADP concentration of 1.0 ?mol/L were significantly associated with incident myocardial infarction/stroke in a multivariable model (hazard ratio, 1.68 [95% confidence interval, 1.13-2.50] [P=0.011] for hyperreactivity across ADP doses; and hazard ratio, 1.16 [95% confidence interval, 1.02-1.33] [P=0.029] for highest quartile of ADP response at 1.0 ?mol/L versus others). No association was observed for collagen lag time or any epinephrine measures with incident myocardial infarction or stroke. CONCLUSIONS:Intrinsic hyperreactivity to low-dose ADP in our community-based sample, who were free of CVD and any antiplatelet therapy, is associated with future arterial thrombosis during a 20-year follow-up. These findings reinforce ADP activation inhibition as a critical treatment paradigm and encourage further study of ADP inhibitor-refractive populations.

SUBMITTER: Puurunen MK

PROVIDER: S-EPMC5866343 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

ADP Platelet Hyperreactivity Predicts Cardiovascular Disease in the FHS (Framingham Heart Study).

Puurunen Marja K MK Hwang Shih-Jen SJ Larson Martin G MG Vasan Ramachandran S RS O'Donnell Christopher J CJ Tofler Geoffrey G Johnson Andrew D AD

Journal of the American Heart Association 20180303 5

<h4>Background</h4>Platelet function is associated with adverse events in patients with cardiovascular disease (CVD).<h4>Methods and results</h4>We examined associations of baseline platelet function with incident CVD events in the community-based FHS (Framingham Heart Study). Participants free of prevalent CVD and without recent aspirin treatment with available data in the Framingham Offspring cohort (1991-1995) and Omni cohort (1994-1998) were included. Platelet function was measured with ligh ...[more]

PMID: 29502103

Similar Datasets

Project description:The Framingham Heart Study (FHS) has conducted seminal research defining cardiovascular disease (CVD) risk factors and fundamentally shaping public health guidelines for CVD prevention over the past five decades. The success of the Original Cohort, initiated in 1948, paved the way for further epidemiological research in preventive cardiology. Due to the keen observations suggesting the role of shared familial factors in the development of CVD, in 1971 the FHS began enroling the second generation cohort, comprising the children of the Original Cohort and the spouses of the children. In 2002, the third generation cohort, comprising the grandchildren of the Original Cohort, was initiated to additionally explore genetic contributions to CVD in greater depth. Additionally, because of the predominance of White individuals of European descent in the three generations of FHS participants noted above, the Heart Study enrolled the OMNI1 and OMNI2 cohorts in 1994 and 2003, respectively, aimed to reflect the current greater racial and ethnic diversity of the town of Framingham. All FHS cohorts have been examined approximately every 2-4 years since the initiation of the study. At these periodic Heart Study examinations, we obtain a medical history and perform a cardiovascular-focused physical examination, 12-lead electrocardiography, blood and urine samples testing and other cardiovascular imaging studies reflecting subclinical disease burden.The FHS has continually evolved along the cutting edge of cardiovascular science and epidemiological research since its inception. Participant studies now additionally include study of cardiovascular imaging, serum and urine biomarkers, genetics/genomics, proteomics, metabolomics and social networks. Numerous ancillary studies have been established, expanding the phenotypes to encompass multiple organ systems including the lungs, brain, bone and fat depots, among others. Whereas the FHS was originally conceived and designed to study the epidemiology of cardiovascular disease, it has evolved over the years with staggering expanded breadth and depth that have far greater implications in the study of the epidemiology of a wide spectrum of human diseases. The FHS welcomes research collaborations using existing or new collection of data. Detailed information regarding the procedures for research application submission and review are available at [http://www.framinghamheartstudy.org/researchers/index.php].

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.

Dataset Information

ADP Platelet Hyperreactivity Predicts Cardiovascular Disease in the FHS (Framingham Heart Study).

Publications

ADP Platelet Hyperreactivity Predicts Cardiovascular Disease in the FHS (Framingham Heart Study).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets