Clinical significance of vascular ageing patterns and blood pressure responses to submaximal exercise in the community

Abstract Background Exaggerated or hypotensive blood pressure (BP) responses to submaximal exercise are associated with increased risk for cardiovascular disease.1 However, beyond cardiorespiratory fitness, the risk factors of these abnormal BP responses to submaximal exercise are poorly known. We hypothesized that vascular ageing (VA) patterns that encompass several functional and structural changes could contribute to these abnormal exercise BP responses. Purpose To examine the contribution and clinical significance of VA patterns to submaximal exercise BP responses in the community. Methods Carotid echotracking was performed in a large community-based cohort of the Paris Prospective Study III. Hierarchical clustering was used to identify VA patterns among ten VA manifestations including carotid pulse wave velocity, Young’s elastic modulus, β stiffness, central pulse pressure, distensibility coefficient, intima-media thickness, circumferential wall stress, wall cross-sectional area, plaque presence, and external diameter. Identified patterns were: healthy vascular ageing (HVA; less stiffness/atherosclerosis); arteriosclerosis (ART; greater stiffness); or atherosclerosis (ATH; greater atherosclerosis). BP was measured at rest and immediately after a 2-minute submaximal step-test. Multivariable multinomial regression evaluated associations between VA patterns and exaggerated (≥150 mmHg systolic BP) and hypotensive (systolic BP below resting level) exercise responses. Clinical significance was determined by multivariable Cox analysis estimating associations (hazard ratios, HRs) between group combinations of VA patterns and BP responses to exercise and major adverse cardiovascular events (MACE). Results Among the 7,689 participants (39% female, mean age 59.2 years, 32.3% hypertensive), 50.5% had HVA, 23.4% ART, and 26.1% ATH. Compared to HVA, ART and ATH patterns were more likely to have hypotensive (ATH:OR 1.69,95% CI 1.22-2.34; ART:OR 2.41; 95% CI 1.77-3.29) and exaggerated (ATH:OR 1.50, 95% CI 1.31-1.71; ART:OR 1.70, 95% CI 1.48-1.96) exercise BP responses after adjusting for age, sex, BMI, smoking status, alcohol intake, total cholesterol, high-density cholesterol, resting heart rate, antihypertensive medication, exercise intensity and cardiorespiratory fitness. Compared to participants with HVA and normal BP response, those with abnormal BP responses and VA patterns of HVA (HR 1.45:95% CI: 1.01-2.15), ATH (HR 2.03;95% CI 1.43-2.89) and ART (HR 2.06; 95% CI 1.44-2.94) had an increased risk of MACE (n=354) over 12 years of follow-up (Figure 1). Conclusions VA patterns reflecting greater arteriosclerosis and greater atherosclerosis are associated with abnormal BP responses to sub maximal exercise including hypotensive and exaggerated BP responses. The significant increased risk of MACE associated with unhealthy VA patterns and abnormal BP responses to submaximal exercise support the clinical significance of the study findings.