The Natural History of Congestive Heart Failure: The Framingham Study

McKee, Patrick A.; Castelli, William P.; McNamara, Patricia; Kannel, William B.

doi:10.1056/nejm197112232852601

Cited by 3,027 publications

(1,717 citation statements)

References 19 publications

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“…We now extend these observations and show that IGFBP1 predicts incident HF, all‐cause mortality, and CVD mortality in our cohort, along with 3 other regulators of metabolic disease and adipocyte function: IGFBP2, adipsin, and leptin. IGFBP2 is the predominant insulin‐like growth factor binding protein (IGFBP) produced by white adipose tissue and is thought to protect against obesity and insulin resistance in mice 8, 22. Previous studies, however, did not demonstrate any relation to CVD outcomes 10, 21.…”

Section: Discussionmentioning

confidence: 99%

“…Cardiovascular events were adjudicated by a 3‐physician panel. Primary outcomes were (1) ASCVD, a composite end point of nonfatal myocardial infarction, revascularization (percutaneous coronary intervention or bypass surgery), atherothrombotic stroke, and coronary heart disease death, (2) HF,8 and (3) all‐cause mortality, with a secondary end point of CVD‐related death.…”

Section: Methodsmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

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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“…Symptomatic HF was defined based on the Framingham criteria,21 and left ventricular ejection fraction (LVEF) was more than 50% 22. Blood samples and echocardiography were obtained at hospital discharge.…”

Section: Methodsmentioning

confidence: 99%

Liver fibrosis score predicts mortality in heart failure patients with preserved ejection fraction

et al. 2017

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AimsHeart failure with preserved ejection fraction (HFpEF) has several pathophysiological aspects, including stiffness and/or congestion of multiple organs. Poor prognosis is expected in heart failure patients with liver stiffness, which has recently been assessed by non‐alcoholic fatty liver disease fibrosis score (NFS; based on aspartate aminotransferase to alanine aminotransferase ratio, platelet counts, and albumin). We aimed to investigate the impact of NFS on prognosis of HFpEF patients, with consideration for the peripheral collagen markers such as procollagen type III peptide (PIIIP), type IV collagen 7S, and hyaluronic acid.Methods and resultsWe performed a prospective observational study. Consecutive 492 hospitalized HFpEF patients were divided into four groups based on their NFS: first–fourth quartiles (n = 123). The fourth quartile group had the highest levels of PIIIP, type IV collagen 7S, hyaluronic acid, and B‐type natriuretic peptide (P<0.001 each). In addition, there were significant positive correlations between PIIIP, type IV collagen 7S, hyaluronic acid, B‐type natriuretic peptide, and NFS (P < 0.001 each). In the follow‐up period (mean 1107 days), 93 deaths occurred. All‐cause mortality increased in all four quartiles (8.1%, 12.2%, 23.6%, and 31.7%, P < 0.001). In the multivariable Cox proportional hazard analysis, NFS was an independent predictor of all‐cause mortality in the HFpEF patients.ConclusionsNFS, a novel indicator of liver fibrosis, correlates with circulating systemic markers of fibrosis and congestion and is associated with higher all‐cause mortality in HFpEF patients. NFS can be calculated simply and may be a useful tool to assess liver stiffness and prognosis in HFpEF patients.

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“…Each suspected CVD event is adjudicated by a panel of 3 physicians who review data from examinations at the Framingham Heart Study, hospitalization records, and physician office visit records 26. Here, we specified 3 primary outcomes of interest: new‐onset CHD (comprising fatal or nonfatal myocardial infarction [MI], coronary insufficiency, and angina pectoris); HF (defined by published criteria27); and all‐cause mortality.…”

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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The Natural History of Congestive Heart Failure: The Framingham Study

Cited by 3,027 publications

References 19 publications

Protein Biomarkers of Cardiovascular Disease and Mortality in the Community

Protein Biomarkers of Cardiovascular Disease and Mortality in the Community

Liver fibrosis score predicts mortality in heart failure patients with preserved ejection fraction

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

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