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70-year legacy of the Framingham Heart Study

Abstract

The Framingham Heart Study (FHS) was established in 1948 to improve understanding of the epidemiology of coronary heart disease (CHD) in the USA. In 1961, seminal work identified major risk factors for CHD (high blood pressure, high cholesterol levels and evidence on the electrocardiogram of left ventricular hypertrophy), which later formed the basis for multivariable 10-year and 30-year risk-prediction algorithms. The FHS cohorts now comprise three generations of participants (n ≈ 15,000) and two minority cohorts. The FHS cohorts are densely phenotyped, with recurring follow-up examinations and surveillance for cardiovascular and non-cardiovascular end points. Assessment of subclinical disease and physiological profiling of these cohorts (with the use of echocardiography, ambulatory electrocardiographic monitoring, exercise stress testing, cardiac CT, heart and brain MRI, serial vascular tonometry and accelerometry) have been performed repeatedly. Over the past decade, the FHS cohorts have undergone deep ‘omics’ profiling (including whole-genome sequencing, DNA methylation analysis, transcriptomics, high-throughput proteomics and metabolomics, and microbiome studies). The FHS is a rich, longitudinal, transgenerational and deeply phenotyped cohort study with a sustained focus on state-of-the-art epidemiological methods and technological advances to facilitate scientific discoveries.

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Acknowledgements

The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the US National Heart, Lung, and Blood Institute (NHLBI), the NIH or the US Department of Health and Human Services. The Framingham Heart Study (FHS) acknowledges the support of contracts NO1-HC-25195 and HHSN268201500001I from the NHLBI and grant supplement R01 HL092577-06S1 for this research. The authors also acknowledge the dedication of the FHS study participants, without whom this research would not be possible. E.J.B. is supported by NIH grants R01 HL128914, 2R01 HL092577, 2U54 HL120163 and 1R01 HL141434 01A1 and AHA grant 18SFRN34110082. R.S.V. is supported in part by the Evans Medical Foundation and the Jay and Louis Coffman Endowment from the Department of Medicine, Boston University School of Medicine, USA.

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All the authors researched data for the article. C.A. and R.S.V. discussed its content. C.A. wrote the initial version of the manuscript, and the other authors reviewed and edited the manuscript before submission.

Correspondence to Charlotte Andersson or Ramachandran S. Vasan.

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Nature Reviews Cardiology thanks B. Psaty, C. Torp-Pedersen, and the other anonymous reviewer(s), for their contribution to the peer review of this work.

Related links

Biologic Specimen and Data Repository Information Coordinating Center: https://biolincc.nhlbi.nih.gov/studies/framcohort/

Cross-Cohort Collaboration Consortium: https://chs-nhlbi.org/node/6539

Database of Genotypes and Phenotypes: https://www.ncbi.nlm.nih.gov/gap

Grand Opportunity Exome Sequencing Project: https://esp.gs.washington.edu/

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Fig. 1: Timeline of the Framingham Heart Study.
Fig. 2: Major publications from the Framingham Heart Study.
Fig. 3: Temporal developments in molecular epidemiology in the Framingham Heart Study.