Microvascular Inflammation and Cardiovascular Prevention: The Role of Microcirculation as Earlier Determinant of Cardiovascular Risk

Healthcare systems encumbered by cardiovascular diseases demand adequate cardiovascular prevention. Indeed, even with the most novel therapies, the residual cardiovascular risk still fuels morbidity and mortality. Addressing inflammation as a putative mediator of this risk has brought along promising in vitro results, though large clinical trials have only in part confirmed them. To fully exploit the therapeutic potential between the inflammatory hypothesis, a change of viewpoint is required. Focus on microcirculation, whose dysfunction is the primary driver of cardiometabolic disease, is mandatory. Several factors play a pivotal role in the capacity of microvascular inflammation to promote a health-to-disease transition: the adipose tissue (in particular, perivascular and epicardial), the mitochondria function, the hyperglycemic damage and their epigenetic signature. Indeed, the low-grade inflammatory response, which is now an acknowledged hallmark of cardiometabolic disease, is promoted by these mediators and leaves a permanent epigenetic scar on the microvasculature. Even if a more profound knowledge about the mechanisms of metabolic memory has been brought to light by recent evidence, we still have to fully understand its mechanisms and clinical potential. Addressing the detrimental role of inflammation by targeting the microvascular phenotype and leveraging epigenetics is the road down which we must go to achieve satisfactory cardiovascular prevention, ultimately leading to disease-free ageing