An Investigation of Coronary Heart Disease in Families

Kannel, William B.; Feinleib, Manning; McNamara, Patricia; Garrison, Robert J.; Castelli, William P.

doi:10.1093/oxfordjournals.aje.a112813

Cited by 1,548 publications

(1,197 citation statements)

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“…The Offspring cohort was recruited beginning in 1971 and the Third Generation cohort started in 2002. We included participants in the Offspring cohort attending the seventh examination cycle (1998–2001, n=3539) and Third Generation participants attending their first examination (2002–2005, n=4095) 4, 5. Because deaths and CVD events were exceedingly rare in individuals aged <50 years, we excluded individuals below this age (n=3833).…”

Section: Methodsmentioning

confidence: 99%

Protein Biomarkers of Cardiovascular Disease and Mortality in the Community

Lyass

Courchesne

et al. 2018

JAHA

221

228

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BackgroundThe discovery of novel and highly predictive biomarkers of cardiovascular disease (CVD) has the potential to improve risk‐stratification methods and may be informative regarding biological pathways contributing to disease.Methods and ResultsWe used a discovery proteomic platform that targeted high‐value proteins for CVD to ascertain 85 circulating protein biomarkers in 3523 Framingham Heart Study participants (mean age, 62 years; 53% women). Using multivariable‐adjusted Cox models to account for clinical variables, we found 8 biomarkers associated with incident atherosclerotic CVD, 18 with incident heart failure, 38 with all‐cause mortality, and 35 with CVD death (false discovery rate, q<0.05 for all; P‐value ranges, 9.8×10−34 to 3.6×10−2). Notably, a number of regulators of metabolic and adipocyte homeostasis were associated with cardiovascular events, including insulin‐like growth factor 1 (IGF1), insulin‐like growth factor binding protein 1 (IGFBP1), insulin‐like growth factor binding protein 2 (IGFBP2), leptin, and adipsin. In a multimarker approach that accounted for clinical factors, growth differentiation factor 15 (GDF15) was associated with all outcomes. In addition, N‐terminal pro‐b‐type natriuretic peptide, C‐reactive protein, and leptin were associated with incident heart failure, and C‐type lectin domain family 3 member B (CLEC3B; tetranectin), N‐terminal pro‐b‐type natriuretic peptide, arabinogalactan protein 1 (AGP1), soluble receptor for advanced glycation end products (sRAGE), peripheral myelin protein 2 (PMP2), uncarboxylated matrix Gla protein (UCMGP), kallikrein B1 (KLKB1), IGFBP2, IGF1, leptin receptor, and cystatin‐C were associated with all‐cause mortality in a multimarker model.ConclusionsWe identified numerous protein biomarkers that predicted cardiovascular outcomes and all‐cause mortality, including biomarkers representing regulators of metabolic homeostasis and inflammatory pathways. Further studies are needed to validate our findings and define clinical utility, with the ultimate goal of improving strategies for CVD prevention.

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Section: Methodsmentioning

confidence: 99%

Protein Biomarkers of Cardiovascular Disease and Mortality in the Community

Lyass

Courchesne

et al. 2018

JAHA

221

228

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“…The study design and selection criteria of the Framingham Offspring cohort has been described elsewhere 32. We included 2035 participants from the Offspring cohort seventh examination (1998–2001) and/or eighth examination (2005–2008) who were not current smokers and had at least one valid measurement of plasma myeloperoxidase or urinary creatinine‐indexed 8‐epi‐PGF 2α (3386 observations in total).…”

Section: Methodsmentioning

confidence: 99%

Short‐Term Exposure to Air Pollution and Biomarkers of Oxidative Stress: The Framingham Heart Study

Wilker

Dorans

et al. 2016

JAHA

122

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BackgroundShort‐term exposure to elevated air pollution has been associated with higher risk of acute cardiovascular diseases, with systemic oxidative stress induced by air pollution hypothesized as an important underlying mechanism. However, few community‐based studies have assessed this association.Methods and ResultsTwo thousand thirty‐five Framingham Offspring Cohort participants living within 50 km of the Harvard Boston Supersite who were not current smokers were included. We assessed circulating biomarkers of oxidative stress including blood myeloperoxidase at the seventh examination (1998–2001) and urinary creatinine‐indexed 8‐epi‐prostaglandin F2α (8‐epi‐PGF 2α) at the seventh and eighth (2005–2008) examinations. We measured fine particulate matter (PM 2.5), black carbon, sulfate, nitrogen oxides, and ozone at the Supersite and calculated 1‐, 2‐, 3‐, 5‐, and 7‐day moving averages of each pollutant. Measured myeloperoxidase and 8‐epi‐PGF 2α were loge transformed. We used linear regression models and linear mixed‐effects models with random intercepts for myeloperoxidase and indexed 8‐epi‐PGF 2α, respectively. Models were adjusted for demographic variables, individual‐ and area‐level measures of socioeconomic position, clinical and lifestyle factors, weather, and temporal trend. We found positive associations of PM 2.5 and black carbon with myeloperoxidase across multiple moving averages. Additionally, 2‐ to 7‐day moving averages of PM 2.5 and sulfate were consistently positively associated with 8‐epi‐PGF 2α. Stronger positive associations of black carbon and sulfate with myeloperoxidase were observed among participants with diabetes than in those without.ConclusionsOur community‐based investigation supports an association of select markers of ambient air pollution with circulating biomarkers of oxidative stress.

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“…The study design and sampling of the Framingham Offspring Study and the Framingham Omni Study have been described 20, 21, 22. Offspring Study participants who attended examination cycle 8 (2005–2008) and Omni Study participants who attended examination cycle 3 (2007–2008) underwent a standardized medical history and examination (N=3319) and 3185 underwent routine echocardiography with digital image acquisition.…”

Section: Methodsmentioning

confidence: 99%

Distinct Aspects of Left Ventricular Mechanical Function Are Differentially Associated With Cardiovascular Outcomes and All‐Cause Mortality in the Community

Cheng

McCabe

Larson

et al. 2015

JAHA

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BackgroundThere are few data relating novel measures of left ventricular (LV) mechanical function to cardiovascular disease (CVD) outcomes in the community. Whether distinct components of LV mechanical function provide information regarding risk for different CVD outcomes is unclear.Methods and ResultsWe used speckle tracking echocardiography to quantify distinct components of LV mechanical function (measured as LV strain in multiple planes) in 2831 Framingham Offspring Study participants (mean age, 66 years; 57% women, 97% with LV fractional shortening >0.29). Participants were followed for 6.0±1.2 years for onset of 69 coronary heart disease (CHD), 71 heart failure (HF), and 199 mortality events. Adjusting for CVD risk factors, longitudinal LV strain appeared associated with incident CHD (hazards ratio [HR] per SD increment, 1.29; 95% confidence interval [CI], 1.00–1.67; P=0.05), whereas circumferential and radial strain were not (P>0.37 for both); however, the association of longitudinal strain with CHD was nonsignificant after Bonferroni correction. By contrast, circumferential strain was a significant predictor of incident HF (HR per SD increment, 1.79; 95% CI, 1.35–2.37; P<0.0001). Decrements in circumferential, radial, and longitudinal strain measures were related to all‐cause mortality (P<0.008 for all). Results remained similar in multivariable models adjusting additionally for the conventional echocardiographic measures of LV mass and fractional shortening.ConclusionsIn our large, community‐based sample, distinct components of LV mechanical function were associated with specific CVD outcomes. Additional studies are needed to replicate these findings and investigate the prognostic and therapeutic utility of these novel measures of LV mechanical function.

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An Investigation of Coronary Heart Disease in Families

Cited by 1,548 publications

References 0 publications

Protein Biomarkers of Cardiovascular Disease and Mortality in the Community

Protein Biomarkers of Cardiovascular Disease and Mortality in the Community

Short‐Term Exposure to Air Pollution and Biomarkers of Oxidative Stress: The Framingham Heart Study

Distinct Aspects of Left Ventricular Mechanical Function Are Differentially Associated With Cardiovascular Outcomes and All‐Cause Mortality in the Community

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