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Early Contributors to Healthy Arterial Aging Versus Premature Atherosclerosis in Young Adults: The Bogalusa Heart Study.

ABSTRACT: Background Early identification of healthy arterial aging versus premature atherosclerosis is important for optimal atherosclerotic cardiovascular disease risk stratification and prevention. We sought to identify predictors for the long-term absence of carotid plaque among young adults. Methods and Results We included 508 participants from the Bogalusa Heart Study without clinical atherosclerotic cardiovascular disease who were free of carotid plaque at baseline (2001-2002) and underwent ultrasound imaging at follow-up (2013-2016). Modified Poisson regression estimated the persistent absence of plaque over 12.8 years. Participants were on average age 36.2 years at baseline, 64% were women, and 29% were Black. Although nearly all participants (97%) had a 10-year atherosclerotic cardiovascular disease risk <7.5%, there were 162 people (32%) who developed premature atherosclerosis. Aside from younger age (risk ratio [RR], 1.21; 95% CI, 1.07-1.36, per 10 years) and a total cholesterol/high-density lipoprotein cholesterol ratio <3.5 (RR, 1.15; 95% CI, 1.01-1.30), normal values of traditional risk factors did not predict long-term absence of plaque. Independent from traditional markers including glomerular filtration rate, serum calcium-phosphate product (RR, 1.07; 95% CI, 1.01-1.14, per 1-SD lower), phosphate (RR, 1.15; 95% CI, 1.03-1.29, per 1 mg/dL lower), and dietary sodium <2300 mg/day (RR, 1.20; 95% CI, 1.02-1.41) were significantly associated with the non-development of plaque. Conclusions Nearly one third of young adults with a low burden of traditional risk factors developed premature atherosclerosis. Beyond younger age and an ideal lipoprotein profile, lower calcium-phosphate homeostasis and low sodium intake were associated with long-term absence of carotid plaque. These results suggest that dietary and intrinsic minerals are early contributors to the development of arterial aging phenotypes.

SUBMITTER: Razavi AC

PROVIDER: S-EPMC8477892 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:INTRODUCTION:Chronic kidney disease (CKD) is a major public health challenge given its high global prevalence and associated risks of cardiovascular disease and progression to end stage renal disease. Although it is known that numerous metabolic changes occur in CKD patients, identifying novel metabolite associations with kidney function may enhance our understanding of the physiologic pathways relating to CKD. OBJECTIVES:The objective of this study was to elucidate novel metabolite associations with kidney function among participants of two community-based cohorts with carefully ascertained metabolomics, kidney function, and covariate data. METHODS:Untargeted ultrahigh-performance liquid chromatography-tandem mass spectrometry was used to detect and quantify blood metabolites. We used multivariate adjusted linear regression to examine associations between single metabolites and creatinine-based estimated glomerular filtration rate (eGFRcr) among 1243 Bogalusa Heart Study (BHS) participants (median eGFRcr: 94.4, 5th-95th percentile: 66.0-119.6 mL/min/1.73 m2). Replication, determined by statistical significance and consistent effect direction, was tested using gold standard measured glomerular filtration rate (mGFR) among 260 Multi-Ethnic Study of Atherosclerosis (MESA) participants (median mGFR: 72.0, 5th-95th percentile: 43.5-105.0 mL/min/1.73 m2). All analyses used Bonferroni-corrected alpha thresholds. RESULTS:Fifty-one novel metabolite associations with kidney function were identified, including 12 from previously unrelated sub-pathways: N6-carboxymethyllysine, gulonate, quinolinate, gamma-CEHC-glucuronide, retinol, methylmalonate, 3-hydroxy-3-methylglutarate, 3-aminoisobutyrate, N-methylpipecolate, hydroquinone sulfate, and glycine conjugates of C10H12O2 and C10H14O2(1). Significant metabolites were generally inversely associated with kidney function and smaller in mass-to-charge ratio than non-significant metabolites. CONCLUSION:The 51 novel metabolites identified may serve as early, clinically relevant, kidney function biomarkers.

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Early Contributors to Healthy Arterial Aging Versus Premature Atherosclerosis in Young Adults: The Bogalusa Heart Study.

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