Age-related structural remodelling of the coronary microcirculation

BackgroundWhile 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. MethodsThis 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 25th percentile) in each group. ResultsThe three study groups were defined as having 37-53; 54-66 and 67-77 years of age, respectively. Oldest (3rd 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] x106 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 25th percentile increased with age (25.0%, vs 52.0% vs 72.7%, for the 1st, 2nd and 3rd age tertiles, respectively, p=0.010). ConclusionsAgeing 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 PERSPECTIVEWhat is new? O_LIAgeing is independently associated with structural remodelling of the coronary microcirculation. C_LIO_LICoronary structural microcirculatory remodelling is reflected by reductions in the Backward Expansion Wave intensity and in Diastolic Microvascular Conductance. C_LI What are the clinical implications? O_LIlder patients exhibit lower hyperemic flow response to pharmacological hyperemia. C_LIO_LIcan explain the observed age-related differences between hyperemic and non-hyperemic indices of functional stenosis classification. C_LI