Dataset Information

Soluble Neprilysin in the General Population: Clinical Determinants and Its Relationship to Cardiovascular Disease.

ABSTRACT: Background Neprilysin is a metalloprotease involved in proteolysis of numerous peptides, including natriuretic peptides, and is of prognostic and therapeutic importance in heart failure with reduced ejection fraction. No studies have investigated circulating neprilysin in the community, its clinical correlates, or its relationship to cardiovascular disease in the general population. Methods and Results Plasma neprilysin was measured in 1536 participants from Olmsted County, Minnesota, using a commercially available sandwich ELISA assay. Clinical and echocardiographic correlates and subsequent outcomes were determined. Soluble neprilysin is non-normally distributed in the community (median: 3.9 ng/mL; interquartile range: 1.0-43.0 ng/mL). There was no relationship between plasma neprilysin and age (Spearman correlation: -0.04, P=0.16); body mass index (Spearman correlation: -0.04, P=0.16); glomerular filtration rate (Spearman correlation: -0.007, P=0.8); or A-, B-, or C-type natriuretic peptides (Spearman correlation: 0.03, P=0.22; -0.001, P=0.96; 0.01, P=0.67, respectively). Among tertiles of neprilysin, the lowest tertile group had the highest prevalence of smokers (P<0.001), hypertension (P=0.04), dyslipidemia (P=0.03), and diastolic dysfunction (P=0.02). Soluble neprilysin was not prospectively associated with death or heart failure over a median of 10.7 years. Conclusions In a large community-based cohort, for the first time, we described the distribution of circulating neprilysin in the general community. We observed that neprilysin does not correlate with natriuretic peptide levels and is not independently associated with adverse outcomes. The novel associations observed between low soluble neprilysin levels and an adverse cardiometabolic and smoking profile requires further investigation.

SUBMITTER: Reddy YNV

PROVIDER: S-EPMC6761669 | biostudies-other | 2019 Aug

REPOSITORIES: biostudies-other

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Soluble Neprilysin in the General Population: Clinical Determinants and Its Relationship to Cardiovascular Disease.

Reddy Yogesh N V YNV Iyer Seethalakshmi R SR Scott Christopher G CG Rodeheffer Richard J RJ Bailey Kent K Jenkins Gregory G Batzler Anthony A Redfield Margaret M MM Burnett John C JC Pereira Naveen L NL

Journal of the American Heart Association 20190726 15

Background Neprilysin is a metalloprotease involved in proteolysis of numerous peptides, including natriuretic peptides, and is of prognostic and therapeutic importance in heart failure with reduced ejection fraction. No studies have investigated circulating neprilysin in the community, its clinical correlates, or its relationship to cardiovascular disease in the general population. Methods and Results Plasma neprilysin was measured in 1536 participants from Olmsted County, Minnesota, using a co ...[more]

PMID: 31345101

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Project description:Objective To provide an overview of prediction models for risk of cardiovascular disease (CVD) in the general population.Design Systematic review.Data sources Medline and Embase until June 2013.Eligibility criteria for study selection Studies describing the development or external validation of a multivariable model for predicting CVD risk in the general population.Results 9965 references were screened, of which 212 articles were included in the review, describing the development of 363 prediction models and 473 external validations. Most models were developed in Europe (n=167, 46%), predicted risk of fatal or non-fatal coronary heart disease (n=118, 33%) over a 10 year period (n=209, 58%). The most common predictors were smoking (n=325, 90%) and age (n=321, 88%), and most models were sex specific (n=250, 69%). Substantial heterogeneity in predictor and outcome definitions was observed between models, and important clinical and methodological information were often missing. The prediction horizon was not specified for 49 models (13%), and for 92 (25%) crucial information was missing to enable the model to be used for individual risk prediction. Only 132 developed models (36%) were externally validated and only 70 (19%) by independent investigators. Model performance was heterogeneous and measures such as discrimination and calibration were reported for only 65% and 58% of the external validations, respectively.Conclusions There is an excess of models predicting incident CVD in the general population. The usefulness of most of the models remains unclear owing to methodological shortcomings, incomplete presentation, and lack of external validation and model impact studies. Rather than developing yet another similar CVD risk prediction model, in this era of large datasets, future research should focus on externally validating and comparing head-to-head promising CVD risk models that already exist, on tailoring or even combining these models to local settings, and investigating whether these models can be extended by addition of new predictors.

Project description:BackgroundWhile data from primary care suggest an insufficient control of vascular risk factors, little is known about vascular risk factor control in the general population. We therefore aimed to investigate the adoption of adequate risk factor control and its determinants in the general population free of cardiovascular disease (CVD).MethodsData from the Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB) Cohort Study, a population-based study of inhabitants aged 30 to 79 years from the general population of Würzburg (Germany), were used. Proportions of participants without established CVD meeting targets for risk factor control recommended by 2016 ESC guideline were identified. Determinants of the accumulation of insufficiently controlled vascular risk factors (three or more) were assessed.ResultsBetween December 2013 and April 2015, 1379 participants without CVD were included; mean age was 53.1 ± 11.9 years and 52.9% were female; 30.8% were physically inactive, 55.2% overweight, 19.3% current smokers. Hypertension, dyslipidemia, and diabetes mellitus were prevalent in 31.8%, 57.6%, and 3.9%, respectively. Treatment goals were not reached despite medication in 52.7% of hypertensive, in 37.3% of hyperlipidemic and in 44.0% of diabetic subjects. Insufficiently controlled risk was associated with male sex (OR 1.94, 95%CI 1.44-2.61), higher age (OR for 30-39 years vs. 70-79 years 4.01, 95%CI 1.94-8.31) and lower level of education (OR for primary vs. tertiary 2.15, 95%CI 1.48-3.11).ConclusionsIn the general population, prevalence of vascular risk factors was high. We found insufficient identification and control of vascular risk factors and a considerable potential to improve adherence to cardiovascular guidelines for primary prevention. Further studies are needed to identify and overcome patient- and physician-related barriers impeding successful control of vascular risk factors in the general population.

Dataset Information

Soluble Neprilysin in the General Population: Clinical Determinants and Its Relationship to Cardiovascular Disease.

Publications

Soluble Neprilysin in the General Population: Clinical Determinants and Its Relationship to Cardiovascular Disease.

Similar Datasets

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