NHLBI TOPMed: Trans-Omics for Precision Medicine (TOPMed) Whole Genome Sequencing Project: Cardiovascular Health Study

Participants from the Cardiovascular Health Study (CHS), a large population-based longitudinal cohort study (phs000287), have been included in the TOPMed project. Whole genome sequencing will be performed to contribute to multiple analyses, including cardiovascular disease risk factors, subclinical disease measures, the occurrence of myocardial infarction (MI) and stroke, and analyses of venous thromboembolism (VTE).Comprehensive phenotypic and pedigree data for study participants are available through dbGaP phs000287.]]>
TOPMed Whole Genome Sequencing Methods: Freeze 9TOPMed Whole Genome Sequencing Methods: Freeze 10For TOPMed, CHS participants were initially included if they had appropriate consent, available DNA, and met any of the following criteria: had an adjudicated idiopathic VTE event during follow-up were African American had an incident MI or definite fatal coronary heart disease (CHD) event during follow-up had a probable fatal CHD event during follow-up had an incident stroke during follow-up had a prevalent MI or stroke at baseline, or were part of a random sample of "healthy elderly" participants who survived free of an MI or stroke. Selection of participants proceeded in a hierarchical manner from criteria a-g without replacement. Each participant was thus assigned to one, and only one, of the seven groups. Additional CHS participants were included in a second set if they had appropriate consent, had available DNA, and had no TOPMed sequencing. This second set of participants was assigned to an eighth “other” group. Follow-up for MI, stroke, and CHD events occurred from baseline in 1989-1990 or 1992-1993 through June 30, 2014. Follow-up for VTE events occurred from baseline (1989-1990 or 1992-1993) through December 31, 2001. CHS publications describe the methods for prevalent (PMID: 8520708) and incident events (PMID: 26538580). VTE includes both deep vein thrombosis (DVT) in which a blood clot forms in a vein deep in the body, and pulmonary embolism (PE) where a blood clot travels to the lungs and blocks blood flow. The objectively diagnosed DVT and PE cases were confirmed by venous or pulmonary imaging, pathology examination of the thrombus removed at surgery, or by autopsy. In addition, many CHS participants have had other cardiovascular events, including atrial fibrillation (AF), angina, and heart failure (HF). ]]>
The Cardiovascular Health Study is an NHLBI-funded observational study of risk factors for cardiovascular disease in adults 65 years of age or older conducted across four US field centers. The original cohort of 5201 persons was recruited in 1989-1990 from random samples of the Medicare eligibility lists. An additional 687 participants, nearly all African Americans, were enrolled in 1992-1993, for a total sample of 5888. Starting in 1989, and continuing through 1999, participants underwent annual extensive clinical examinations. Follow-up for events remains ongoing through the present. The identification of VTE in CHS was conducted as part of the Longitudinal Investigation of Thromboembolism Etiology (LITE), a collaboration between the Atherosclerosis Risk in Communities (ARIC) Study and CHS.]]>