Abstract
BACKGROUND: Elevated blood pressure (BP) is a major contributor to coronary artery disease. We explored the impact of life-course BP on later-life normalized stress myocardial blood flow (sMBF(N)) and myocardial perfusion reserve by cardiovascular magnetic resonance (CMR). METHODS: MyoFit46 prospectively recruited ≈500 National Survey of Health and Development 1946 birth cohort participants, aged ≈77 years, to undergo stress perfusion and late gadolinium enhancement CMR. Systolic (SBPs) and diastolic BPs were recorded at 36, 43, 53, 63, 69, and 77 years. For each participant, the annual rates of BP change (steepness of BP increase) and area under the BP trajectory curve (cumulative life-course BP burden) were derived using mixed-effects models. The associations between BP measures and CMR metrics were tested using generalized linear and additive models, adjusted for antihypertensive use, demographics, lifestyle choices, and comorbidities. Cross-sectional associations between CMR metrics and major adverse cardiovascular events (myocardial infarction, stroke, and heart failure) were also tested. Mediation analyses explored the mechanistic pathways linking life-course BPs, myocardial perfusion, and myocardial fibrosis. RESULTS: Among 459 included MyoFit46 participants, each 10 mm Hg higher SBP at 36 to 69 years was associated with 3% to 6% lower sMBF(N) by CMR at 77 years. At 43 to 63 years, as SBPs rose from 120 to 140 mm Hg, sMBF(N) was 18% to 24% lower. Having a sustained higher SBP by 10 mm Hg from 36 to 77 years was associated with 11% (95% CI, 8-14) lower sMBF(N) at 77 years. Each 1 mm Hg/y steeper SBP rise during age intervals 36 to 43, 43 to 53, 53 to 63, and 63 to 69 years was associated with 2% to 6% lower sMBF(N) at 77 years, associations not conditional on baseline or final BPs in each age interval. Associations may be clinically relevant as each 1% lower sMBF(N) was associated with 3% higher odds of major adverse cardiovascular events. sMBF(N) mediated ≈20% to ≈40% of the associations between life-course SBPs and late gadolinium enhancement at 77 years. Results were similar for diastolic BP, myocardial perfusion reserve, or sMBF (not normalized). CONCLUSIONS: Higher life-course BPs, steeper increases, and greater cumulative BP burden associate with lower myocardial perfusion by CMR at 77 years, which can be linked with higher odds of major adverse cardiovascular events and greater myocardial fibrosis burden. This underscores the importance of early life BP screening and guiding hyperetension treatment based on longitudinal BP trajectories (rather than relying solely on cross-sectional BPs). REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05455125.