HIGHER BLOOD PRESSURE ACROSS THE LIFE COURSE CAN BE LINKED TO REDUCED MYOCARDIAL PERFUSION IN OLDER AGE

Abstract

Background High blood pressure (BP) leads to coronary artery disease, yet the impact of life course BP on later-life myocardial blood flow (MBF) and perfusion reserve (MPR) remains elusive. In this study, we aimed to explore the link between life course BP and older-age global stress MBF normalized (STRESSMBFgN) to contemporaneous rate pressure product (RPP, where RPP = heart rate x central aortic systolic BP SBP]) and global MPRg. Methods National Survey of Health and Development (NSHD) is a 1946 birth cohort with continuous follow-up. MyoFit46 recruited ~500 NSHD participants for a cardiovascular magnetic resonance (CMR) scan at 74-78 years, assessing left ventricular (LV) structure and function, perfusion (STRESSMBFgN and MPRg), and late gadolinium enhancement (LGE). BPs were recorded at 36, 43, 53, 60-64, 69, and 74- 78 years. BP step changes between two ages, BP trajectories, mean life course BPs, and areas under the BP trajectory curve (AUC-BP) were derived using a mixed-effects natural cubic spline model. Participants were clustered based on their BP trajectories using a latent class mixed model. Associations between these BPs and CMR metrics were tested using generalized linear and additive models (GLMs, GAMs), adjusted for demographics, lifestyle, comorbidities, and antihypertensive use. Mediation analyses explored mechanistic pathways. Results 459 MyoFit46 participants aged 74-78 (53% male) were included. Using GLMs, each 1 mmHg SBP increase at 43, 53, 60-64, 69, and 74-78 years independently associated with a 0.2-0.6% lower STRESSMBFgN (table 1). For 53-69 years SBPs, relationships were non-linear using GAMs, with the steepest STRESSMBFgN decrease observed as SBP rose from 120 to 140mmHg (figure 1). Each 1 mmHg rise in mean life course SBP associated with a 0.9% lower STRESSMBFgN, while each decade spent at 10 mmHg higher SBP (as per AUC-SBP) associated with a 2.1% lower STRESSMBFgN (p<0.001). Each 1 mmHg SBP rise from 43 to 53 years, and from 53 to 60- 64 years, was linked to a 0.3% and 0.5% lower STRESSMBFgN respectively, independent of AUC-SBP (table 2). LV maximal wall thickness (WT) mediated 12-17% of the relationships between life course SBPs and STRESSMBFgN. STRESSMBFgN mediated 21-31% of the SBPs-LV LGE associations. Results were similar when using MPRg (tables 1 and 2), STRESSMBFg (not normalized), or after excluding those on antihypertensives. Figure 2 shows participant clusters based on BP trajectories. Those with steep SBP increases from 36 to 53 years and slower increases after (red line) had worse MPRg (2.5 vs 2.9, p=0.046) compared to those with stable SBPs until 60-64 years, followed by steep increases (orange line). Effect sizes were larger for diastolic and pulse pressures. Conclusion Higher life course BPs, steeper increases, and spending more years with a higher BP associate with worse myocardial perfusion in older-age, partially explained by high BP increasing LV WT. Reduced myocardial perfusion associates with fibrosis, suggesting that certain individuals (e.g., those with higher midlife BP) may benefit from stricter control.