Metabolic Predictors of Change in Vascular Function

Abstract

A rterial stiffness measures predict the onset of hypertension and incident cardiovascular disease (CVD) events. [1][2][3][4][5] Cross-sectional correlates of vascular stiffness include age, sex, weight, blood pressure, height, and metabolic features like fasting glucose and lipid levels. 6 Our previous work demonstrated strong, nonlinear relations between age and aortic stiffness measures, suggesting that aortic stiffness increases over time, particularly after midlife.7 Prior work has shown that age-related trends in average values for risk factors, such as blood pressure, may include effects from aging itself, age-related changes in other risk factor levels, birth cohort effects, or other factors. [8][9][10] CVD risk factors found to be associated with aging-related phenotypes in cross-sectional analyses can differ from observed associations in longitudinal analyses.11 Therefore, we sought to assess the prospective associations of changes in large and small vessel function (as dependent variables) with changes in metabolic traits (as the independent variables) in a large community-based, multiethnic sample of middle-aged and older adults. Based on previously identified cross-sectional associations between metabolic risk factors and vascular function and between older age and worsening vascular function, we hypothesized that longitudinal worsening of metabolic traits would be associated with worsening of large and small vessel function. MethodsData, analytic methods, and study materials are available to other researchers through National Heart, Lung, and Blood Institute BioLINCC repository at https://biolincc.nhlbi.nih.gov/studies/ framcohort/. The study sample consisted of participants in the Framingham Offspring, Omni 1, Third Generation, and Omni 2 cohorts, which have been described in detail. Worsening of each metabolic trait was associated with increases in CFPWV and MAP (P<0.0001 for all associations) and an increase in MAP was associated with an increase in CFPWV. Overall, worsening metabolic traits were associated with worsening aortic stiffness and MAP. Opposite net change in aortic stiffness and MAP suggests that factors other than distending pressure contributed to the observed increase in aortic stiffness. Change in metabolic traits explained a greater proportion of the change in CFPWV and MAP than baseline metabolic values.

Triglycerides and aortic pulse wave velocity in patients with chronic inflammation

“…Moreover, an association between arterial stiffness and triglycerides was also confirmed in subjects with rheumatoid arthritis, as previously reported 3 . Similar results were also reported in a sample of the general population and in patients with metabolic syndrome 4, 5. The relationship between triglycerides and arterial stiffness may involve local and systemic inflammation, oxidative stress and endothelial dysfunction.…”

Aortic stiffness, pressure and flow pulsatility, and target organ damage

“…Furthermore, a 1-unit increase in the American Heart Association's Life's Simple 7 was associated with 1.55-fold odds for the presence of HVA. The components of Life's Simple 7 most closely associated with HVA were obesity and diabetes, which are also associated with longitudinal change in aortic stiffness (103), suggesting that relatively straightforward lifestyle interventions may prevent stiffening (53), promote HVA, and reduce CVD risk.…”

Determinants of pulse wave velocity trajectories from youth to young adulthood

“…Longitudinal studies on PWV progression in adults and the elderly have been reported [19–26]. The majority of these studies measured PWV at baseline and one follow-up, which does not provide a sufficient basis for studying PWV development with age.…”