Age-related structural remodelling of the coronary microcirculation

ABSTRACT Background While it is broadly accepted that ageing is associated with impairment of coronary microvascular function, little is known on the underlying mechanisms. Diastolic microcirculatory conductance (DMVC) and the backward expansion wave (BEW) derived from wave intensity analysis (WIA) are two physiological indices derived from post-analysis of coronary pressure and flow that have been previously validated against endomyocardial biopsy micromorphometry, thus serving as metrics of structural microcirculatory remodelling applicable to in vivo assessment of the human coronary microcirculation. We investigated age-related changes in coronary microvascular structure in patients with stable angina without epicardial coronary stenoses. Methods This is an analysis of the IDEAL registry, including a total of 165 vessels without coronary stenosis interrogated with combined pressure/Doppler guidewires in non-diabetic patients. We calculated DMVCs and BEWs using dedicated software, and we compared them between patient groups according to age tertiles. We also calculated the prevalence of CMD, defined by reduced Coronary Flow Reserve (CFR <2.5), and calculated the prevalence of low BEW and low DMVC (values below the 25 th percentile) in each group. Results The three study groups were defined as having 37-53; 54-66 and 67-77 years of age, respectively. Oldest (3 rd tertile) patients show lower hyperemic flow velocity (46.7±14.4 vs 45.1±12.4 vs 38.4±11.5 cm.s-1, p=0.019), lower DMVC (1.90±0.71 vs 1.44±0.56 vs 1.37±0.67 cm.s -1 .mmHg -1 , p<0.001) and lower BEW intensity (5.9 [2.9-8.4] vs 4.8 [2.9-6.8] vs 4.4 [3.4-6.3] x10 6 W.m -2 .s -1 , p=0.094). Older age was also found to be an independent predictor of lower cumulative BEW intensity (B −0.10, 95% CI: −0.17 to −0.09, p=0.021) and lower DMVC (B −0.25 95% CI: −0.45 to −0.09, p=0.027). In patients with CMD as determined by CFR <2.5, the prevalence of BEW intensity and DMVC below the 25 th percentile increased with age (25.0%, vs 52.0% vs 72.7%, for the 1 st , 2 nd and 3 rd age tertiles, respectively, p=0.010). Conclusions Ageing is independently associated with structural microcirculatory remodelling that is reflected in BEW intensity and DMVC measurements and increased prevalence of structural CMD. These results are important in understanding non-obstructive mechanisms of myocardial ischemia in the elderly. CLINICAL PERSPECTIVE What is new? Ageing is independently associated with structural remodelling of the coronary microcirculation. Coronary structural microcirculatory remodelling is reflected by reductions in the Backward Expansion Wave intensity and in Diastolic Microvascular Conductance. What are the clinical implications? lder patients exhibit lower hyperemic flow response to pharmacological hyperemia. can explain the observed age-related differences between hyperemic and non-hyperemic indices of functional stenosis classification.