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Long-Term Burden of Higher Body Mass Index and Adult Arterial Stiffness Are Linked Predominantly Through Elevated Blood Pressure.

ABSTRACT: Obesity and hypertension are important risk factors of arterial stiffness. However, the complex relationship between increased body mass index (BMI), elevated blood pressure (BP), and arterial stiffness is largely unknown. We aim to examine the mediation effect of elevated BP on the association of early life BMI, long-term burden, and trend of BMI with arterial stiffness in midlife. The longitudinal study cohort consisted of 1190 participants (829 whites and 361 blacks, 518 males, mean age=40.0 years at follow-up) who had been examined for BMI and BP 4 to 15 times from childhood and aortic-femoral pulse wave velocity (afPWV) in adulthood, with a mean follow-up period of 30.3 years. Total area under the curve (AUCt) and incremental AUC (AUCi) were calculated in random-effects models and used as long-term measures of BMI and BP. Total effects of BMI measures on adult afPWV, adjusted for covariates were all significant without adult BMI and systolic BP (SBP) measures included in the models. The mediation effects of adult SBP (20.2%) and SBP AUCi (16.9%) were significant on the childhood BMI-afPWV association. Adult SBP showed significant mediation effects of 36.7% on the BMI AUCi-afPWV association and 36.4% on the BMI AUCt-afPWV association. The mediation effect of SBP AUCi was estimated at 63.3% ( P<0.01) on the BMI AUCi-afPWV association. Diastolic BP had similar total and mediation effects. These findings suggest that the association of increased childhood BMI and its cumulative burden with adult arterial stiffness measured as afPWV is predominantly mediated through the long-term and increasing trend of BP.

SUBMITTER: Liu Y

PROVIDER: S-EPMC6310035 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Project description:BackgroundAging is the primary risk factor for cardiovascular diseases, the leading cause of death worldwide. Age-related increases in systolic blood pressure (SBP) link advancing age to cardiovascular disease risk. A key mechanism mediating the increase in SBP with aging is stiffening of the large elastic arteries, which occurs due to increases in oxidative stress, inflammation, and vascular smooth muscle tone. Nicotinamide adenine dinucleotide (NAD+) is a key molecule in energy metabolism and cellular functioning which declines with advancing age and chronic disease. Dietary supplementation with NAD+ precursors, such as nicotinamide riboside, boosts NAD+ bioavailability and may improve cardiovascular health. Here, we present the protocol for a randomized, controlled trial investigating the efficacy of 3 months of oral supplementation with nicotinamide riboside for decreasing SBP and arterial stiffness in midlife and older adults with initial above-normal (120-159 mmHg) SBP (ClinicalTrials.gov Identifier: NCT03821623). The primary outcome is casual (resting) SBP and secondary outcomes include 24-h SBP and aortic stiffness. Other outcomes include assessment of safety; tolerability; adherence; diastolic BP; systemic NAD+ bioavailability; and circulating biomarkers of oxidative stress, inflammation, and sympathoadrenal activity.MethodsA randomized, double-blind, placebo-controlled, single-site parallel-group design clinical trial will be conducted in 94 (47/group) midlife and older (age ≥ 50 years) adults with initial above-normal SBP. Participants will complete baseline testing and then will be randomized to either nicotinamide riboside (500 mg, 2×/day, NIAGEN®; ChromaDex Inc.) or placebo supplementation. Outcome measures will be assessed again after 3 months of treatment.DiscussionThis study is designed to establish the safety and efficacy of the NAD+ boosting compound, nicotinamide riboside, for reducing casual and 24-h SBP and aortic stiffness in midlife and older adults with above-normal SBP at baseline, a population at increased risk of cardiovascular diseases.Clinical trial registration[www.ClinicalTrials.gov], identifier [NCT03821623].

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Long-Term Burden of Higher Body Mass Index and Adult Arterial Stiffness Are Linked Predominantly Through Elevated Blood Pressure.

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