Cardiovascular Disease in People with and without Diabetes: Current Trends and Emerging Risk Factors

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide. That can be ascribed to population growth and aging as well as to the ever-increasing prevalence of type 2 diabetes (T2D) and obesity. While death rates from atherosclerotic CVD (ASCVD) among older age groups are falling, the number of persons with heart failure (HF) is projected to increase, and more than half of them have HF with preserved ejection faction (HFpEF). Within this framework, it is necessary to develop incrementally sophisticated risk scores implementing emerging risk factors, for an improved cardiovascular risk estimation and stratification both in people with and without diabetes. This would allow to identify people with higher risk of developing CVD and thus to apply preventive strategies. Such strategies should take into account important sex-differences that concern cardiac and vascular responses to risk factors, CVD burden and mortality. Besides, because the HFpEF epidemic continue to grow and therapeutic interventions being tested are failing, efforts should be directed towards a more accurate diagnosis and definition and improved categorization of phenotypes and stages. The main objectives of this thesis were: 1) to describe trends of CVD in people with diabetes; 2) to evaluate the association between established and emerging risk factors, cardiovascular outcomes and mortality in people with and without diabetes; 3) to investigate the pathophysiological mechanisms of HFpEF in people with and without diabetes and how novel markers can improve its detection. Overall, this thesis indicated that the ongoing epidemics of diabetes and CVD call for improved risk stratification models implementing emerging risk factors, in order to identify people at higher cardiovascular risk. We found that several emerging cardiovascular risk factors such as kidney function measures, vitamin D and K status, could indeed be potentially useful in this regard, as significantly and prospectively associated to measures of cardiovascular health, cardiovascular outcomes and mortality. Some of these associations differed between men and women, suggesting important sex differences in cardiovascular pathophysiology, CVD risk and burden. HFpEF gained a prominent role among CVD both in people with and without diabetes and has emerged as a critical public health problem with increasing prevalence. Accordingly, innovative integrated approaches for the diagnosis of diastolic dysfunction and HFpEF that take into account its phenotypic diversity as well as sex disparities are urgently needed.