Effects of Caffeine and Coffee on Incident Heart Failure in General Population. Role of the CYP1A2 -163C>A Polymorphism

AbstractCirculating cardiac troponin proteins are associated with structural heart disease and predict incident cardiovascular disease in the general population. However, the genetic contribution to cardiac troponin I (cTnI) concentrations and its causal effect on cardiovascular phenotypes is unclear. We combine data from two large population-based studies, the Trøndelag Health Study and the Generation Scotland Scottish Family Health Study and perform a genome-wide association study of high-sensitivity cTnI concentrations with 48 115 individuals. We further used two-sample Mendelian randomization to investigate the causal effects of circulating cTnI on acute myocardial infarction and heart failure.We identified 12 genetic loci (8 novel) associated with cTnI concentrations. Associated protein-altering variants highlighted putative functional genes: CAND2, HABP2, ANO5, APOH, FHOD3, TNFAIP2, KLKB1 and LMAN1. Phenome-wide association tests in 1283 phecodes and 274 continuous traits in UK Biobank showed associations between a polygenic risk score for cTnI and cardiac arrhythmias, aspartate aminotransferase 1 and anthropometric measures. Excluding individuals with a known history of comorbidities did not materially change associations with cTnI. Using two-sample Mendelian randomization we confirmed the non-causal role of cTnI in acute myocardial infarction (5 948 cases, 355 246 controls). We found some indications for a causal role of cTnI in heart failure (47 309 cases and 930 014 controls), but this was not supported by secondary analyses using left ventricular mass as outcome (18 257 individuals).Our findings clarify the biology underlying the heritable contribution to circulating cTnI and support cTnI as a non-causal biomarker for acute myocardial infarction and heart failure development in the general population. Using genetically informed methods for causal inference of cTnI helps inform the role and value of measuring cTnI in the general population.

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Matrix Gla Protein Levels Are Associated With Arterial Stiffness and Incident Heart Failure With Preserved Ejection Fraction

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.121.316664 ◽

2021 ◽

Author(s):

Rajeev Malhotra ◽

Christopher J. Nicholson ◽

Dongyu Wang ◽

Vijeta Bhambhani ◽

Samantha Paniagua ◽

...

Keyword(s):

Heart Failure ◽

Cardiovascular Disease ◽

Arterial Stiffness ◽

Ejection Fraction ◽

Vascular Calcification ◽

Matrix Gla Protein ◽

Preserved Ejection Fraction ◽

Wild Type ◽

Incident Heart Failure

Objective: Arterial stiffness is a risk factor for cardiovascular disease, including heart failure with preserved ejection fraction. MGP (matrix Gla protein) is implicated in vascular calcification in animal models, and circulating levels of the uncarboxylated, inactive form of MGP (ucMGP) are associated with cardiovascular disease-related and all-cause mortality in human studies. However, the role of MGP in arterial stiffness is uncertain. Approach and Results: We examined the association of ucMGP levels with vascular calcification, arterial stiffness including carotid-femoral pulse wave velocity (PWV), and incident heart failure in community-dwelling adults from the Framingham Heart Study. To further investigate the link between MGP and arterial stiffness, we compared aortic PWV in age- and sex-matched young (4-month-old) and aged (10-month-old) wild-type and Mgp +/− mice. Among 7066 adults, we observed significant associations between higher levels of ucMGP and measures of arterial stiffness, including higher PWV and pulse pressure. Longitudinal analyses demonstrated an association between higher ucMGP levels and future increases in systolic blood pressure and incident heart failure with preserved ejection fraction. Aortic PWV was increased in older, but not young, female Mgp +/− mice compared with wild-type mice, and this augmentation in PWV was associated with increased aortic elastin fiber fragmentation and collagen accumulation. Conclusions: This translational study demonstrates an association between ucMGP levels and arterial stiffness and future heart failure with preserved ejection fraction in a large observational study, findings that are substantiated by experimental studies showing that mice with Mgp heterozygosity develop arterial stiffness. Taken together, these complementary study designs suggest a potential role of therapeutically targeting MGP in heart failure with preserved ejection fraction.

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The Role of Reproductive Factors in Risk Prediction of Incident Heart Failure in White and Black Women: The Women's Health Initiative

Journal of Cardiac Failure ◽

10.1016/j.cardfail.2020.09.233 ◽

2020 ◽

Vol 26 (10) ◽

pp. S80

Author(s):

Priya P. Mehta ◽

Hongyan Ning ◽

Amanda M. Perak ◽

Abbi Lane-Cordova ◽

Mercedes Carnethon ◽

...

Keyword(s):

Heart Failure ◽

Black Women ◽

Women's Health ◽

Risk Prediction ◽

Reproductive Factors ◽

Women's Health Initiative ◽

Health Initiative ◽

Incident Heart Failure ◽

The Women’S Health Initiative

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Incident heart failure risk after bariatric surgery: the role of epicardial fat

European Heart Journal ◽

10.1093/eurheartj/ehaa072 ◽

2020 ◽

Vol 41 (18) ◽

pp. 1775-1775 ◽

Cited By ~ 1

Author(s):

Gijs van Woerden ◽

Sophie L van Veldhuisen ◽

Michiel Rienstra

Keyword(s):

Heart Failure ◽

Bariatric Surgery ◽

Epicardial Fat ◽

Failure Risk ◽

Incident Heart Failure

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The metabolites urobilin and sphingomyelin (30:1) are associated with incident heart failure in the general population

ESC Heart Failure ◽

10.1002/ehf2.12453 ◽

2019 ◽

Vol 6 (4) ◽

pp. 764-773 ◽

Cited By ~ 6

Author(s):

Markus Stenemo ◽

Andrea Ganna ◽

Samira Salihovic ◽

Christoph Nowak ◽

Johan Sundström ◽

...

Keyword(s):

Heart Failure ◽

General Population ◽

Incident Heart Failure

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Serum NT-pro-BNP Levels Predict Cardiovascular Events in Acromegaly Patients

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/a-1540-5009 ◽

2021 ◽

Author(s):

Marta Ragonese ◽

Gianluca Di Bella ◽

Federica Spagnolo ◽

Loredana Grasso ◽

Angela Alibrandi ◽

...

Keyword(s):

Heart Failure ◽

General Population ◽

Brain Natriuretic Peptide ◽

Roc Curve ◽

Cardiovascular Events ◽

Roc Analysis ◽

Middle Term ◽

Increased Risk

Abstract Background Acromegaly is associated with an increased risk of fatal and non-fatal cardiovascular (CV) events. Controlling acromegaly decreases, but does not normalize this risk. Brain natriuretic peptide (BNP) assessment is used in the general population for the diagnosis of heart failure and to predict ischemic recurrences and mortality. This is a retrospective, longitudinal, monocenter study that evaluates the role of serum N-terminal fragment of BNP (NT-pro-BNP) for predicting CV events in acromegaly patients. Methods Serum NT-pro-BNP levels were measured in 76 patients with acromegaly (23 males, 57.7±1.5 years), and compared with other predictors of CV events. NT-pro-BNP cut-off value discriminating the occurrence of CV events was determined by ROC analysis. CV events were recorded during a follow-up of 78.6±6.4 months. Results CV events occurred in 9.2% of patients. Mean log(NT-pro-BNP) concentration was higher in patients who experienced CV events than in those who did not (p<0.01) and in patients who died due to CV events than in those who died due to other causes (p<0.01). Based on the ROC curve, a cut-off value of 91.55 pg/mL could predict CV events (OR 19.06). Log(NT-pro-BNP) was lower in surgically treated patients by surgery (p<0.05), and in those cured by neurosurgery (p<0.02). Conclusions High NT-pro-BNP value is an independent middle-term predictor of fatal or non-fatal CV events in patients with acromegaly. According to this parameter, surgically treated patients show lower CV risk than those managed with medical therapy, especially if the disease is cured.

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