Dataset Information

Proteomic Mediators of Overall Cardiovascular Health on All-Cause Mortality.

ABSTRACT: Measures of cardiovascular health (CVH) assessed by a combination of behavioral and biological factors has shown protective associations with all-cause mortality. The mechanisms underlying these associations have not been fully elucidated. In this study, we characterized the plasma proteomics profile of CVH and tested whether specific proteins mediated the associations between CVH and all-cause mortality in participants of the InCHIANTI study. Of the 1301 proteins tested, 92 proteins were associated with CVH (22 positively, 70 negatively). Proteins most strongly associated with CVH included leptin (LEP), fatty acid binding protein 3 (FABP3), Angiopoietin-2 (ANGPT2), and growth-differential factor 15 (GDF15). Of the 92 CVH-associated proteins, 33 proteins significantly mediated the associations between CVH and all-cause mortality, with percent mediation ranging from 5 to 30%. The most significant mediating proteins were GDF15 and insulin-like growth factor 2 (IGFBP2). Proteins associated with better CVH were enriched for proteins that reflect the suppression of the complement coagulation and GH/IGF pathways.

SUBMITTER: Tanaka T

PROVIDER: S-EPMC9921082 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Proteomic Mediators of Overall Cardiovascular Health on All-Cause Mortality.

Tanaka Toshiko T Talegawkar Sameera A SA Jin Yichen Y Candia Julián J Fantoni Giovanna G Bandinelli Stefania S Ferrucci Luigi L

Nutrients 20230203 3

Measures of cardiovascular health (CVH) assessed by a combination of behavioral and biological factors has shown protective associations with all-cause mortality. The mechanisms underlying these associations have not been fully elucidated. In this study, we characterized the plasma proteomics profile of CVH and tested whether specific proteins mediated the associations between CVH and all-cause mortality in participants of the InCHIANTI study. Of the 1301 proteins tested, 92 proteins were associ ...[more]

PMID: 36771486

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Project description:RATIONALE:Although the health effects of beta carotene have been studied extensively, a systematic examination of serum concentrations and long-term mortality, including cardiovascular disease mortality, has not been reported. OBJECTIVE:Explore whether serum beta carotene is associated with overall and cause-specific mortality and to elucidate the strength and dose-response of the association. METHODS AND RESULTS:We conducted a prospective serological analysis of 29?103 men in the ATBC study (Alpha-Tocopherol, Beta-Carotene Cancer Prevention). During 31 years of follow-up, 23?796 deaths occurred, including deaths because of cardiovascular disease (9869), cancer (7692), respiratory disease (2161), diabetes mellitus (119), injuries and accidents (1255), and other causes (2700). Serum beta carotene was assayed using high-performance liquid chromatography. Adjusting for major risk factors measured, men with higher serum beta carotene had significantly lower all-cause mortality (hazard ratios=0.81, 0.71, 0.69, and 0.64 for quintile 2 (Q2)-Q5 versus Q1, respectively; Ptrend<0.0001). Serum beta carotene was significantly associated with risk of death from cardiovascular disease, heart disease, stroke, cancer, respiratory disease, diabetes mellitus, injuries and accidents, and other causes (Q5 versus Q1, hazard ratio=0.21-0.73, all Ptrend<0.0001). The all-cause mortality association was not materially impacted by adjustment for fruit and vegetable consumption (albeit, estimated with some measurement error) and was generally similar across subgroups of smoking intensity, alcohol consumption, trial supplementation, and duration of follow-up, but was significantly modified by age, years of smoking, and body mass index, with stronger inverse associations among men who were younger, smoked fewer years, and had a lower body mass index (all Pinteraction?0.0025). CONCLUSIONS:This study provides evidence that higher beta carotene biochemical status is associated with lower overall, cardiovascular disease, heart disease, stroke, cancer, and other causes of mortality. The dose-response associations over a 30-year period were not attenuated by adjustment for other important risk factors and support greater fruit and vegetable consumption as a means to increase beta carotene status and promote longevity.

Project description:ImportanceAlthough cumulative evidence suggests that elevated urinary albumin-to-creatinine ratio (UACR) in the normal range (<30 mg/g) may be associated with an increased risk of mortality, few studies have investigated whether cardiovascular health (CVH) modifies the harmful outcomes of high-normal UACR.ObjectiveTo investigate associations of traditionally normal UACR and CVH with all-cause mortality.Design, setting, and participantsThis cohort study used National Health and Nutrition Examination Survey data from 2005 through 2018 and linked mortality information until 2019. Data were analyzed from March 1 through October 31, 2023. The study included adult participants aged 20 to 79 years with a normal UACR (<30 mg/g) based on Kidney Disease: Improving Global Outcomes criteria.ExposuresThe UACR was treated as a continuous variable and categorized into tertiles delineated as low (<4.67 mg/g), medium (4.67-7.67 mg/g), and high (7.68 to <30 mg/g). Cardiovascular health was assessed using Life's Essential 8 scores and grouped as poor (0-49 points), moderate (50-79 points), and ideal (80-100 points).Main outcomes and measuresMultivariable Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for associations of UACR with all-cause mortality in total participants and as stratified by CVH groups.ResultsThe study included 23 697 participants (mean [SD] age, 45.58 [15.44] years; 11 806 women [49.7%] and 11 891 men [50.3%]). During the median 7.8 years (range, 4.5-11.1 years) of follow-up, 1403 deaths were recorded. Near-linear associations were observed for continuous UACR and CVH with all-cause mortality. Compared with the low UACR group, high UACR in the normal range showed an increased mortality risk in the moderate and poor CVH groups (CVH [50-79]: HR, 1.54 [95% CI, 1.26-1.89]; CVH [0-49]: HR, 1.56 [95% CI, 1.10-2.20]), with a significant multiplicative interaction of UACR and CVH (P < .001).Conclusions and relevanceThe findings suggest that high UACR within the normal range is associated with a significantly increased risk of all-cause mortality, with the association more pronounced in adults with poor CVH status. These findings highlight the importance of risk management for early kidney dysfunction, particularly among individuals with poor CVH.

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Project description:PurposeConduct a systematic umbrella review to evaluate the relationship of physical activity (PA) with all-cause mortality, cardiovascular mortality, and incident cardiovascular disease (CVD); to evaluate the shape of the dose-response relationships; and to evaluate these relationships relative to the 2008 Physical Activity Guidelines Advisory Committee Report.MethodsPrimary search encompassing 2006 to March, 2018 for existing systematic reviews, meta-analyses, and pooled analyses reporting on these relationships. Graded the strength of evidence using a matrix developed for the Physical Activity Guidelines Advisory Committee.ResultsThe association of self-reported moderate-to-vigorous physical activity (MVPA) on all-cause mortality, CVD mortality, and atherosclerotic CVD-including incident coronary heart disease, ischemic stroke and heart failure-are very similar. Increasing MVPA to guidelines amounts in the inactive US population has the potential to have an important and substantial positive impact on these outcomes in the adult population. The following points are clear: the associations of PA with beneficial health outcomes begin when adopting very modest (one-third of guidelines) amounts; any MVPA is better than none; meeting the 2008 PA guidelines reduces mortality and CVD risk to about 75% of the maximal benefit obtained by physical activity alone; PA amounts beyond guidelines recommendations amount reduces risk even more, but greater amounts of PA are required to obtain smaller health benefits; and there is no evidence of excess risk over the maximal effect observed at about three to five times the amounts associated with current guidelines. When PA is quantified in terms of energy expenditure (MET·h·wk), these relationships hold for walking, running, and biking.ConclusionsTo avoid the risks associated with premature mortality and the development of ischemic heart disease, ischemic stroke, and all-cause heart failure, all adults should strive to reach the 2008 Physical Activity Guidelines for Americans.

Dataset Information

Proteomic Mediators of Overall Cardiovascular Health on All-Cause Mortality.

Publications

Proteomic Mediators of Overall Cardiovascular Health on All-Cause Mortality.

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