Severe-1 Study Protocol: Secondary Prevention and Extreme Cardiovascular Risk Evaluation, Focus on Prevalence and Associated Risk Factors

Abstract

Objective: Despite significant improvement in secondary CV prevention strategies, some Acute and Chronic Coronary Sindrome (ACS and CCS) patients will suffer recurrent CV events (also called “extreme CV risk”). Recently new biochemical markers, such as Uric Acid (UA), Lipoprotein A (LpA) and several markers of inflammation, have been described to be associated with CV events recurrence. We proposed a study (SEVERE-1) for the accurate characterization of extreme CV risk patients enrolled in Cardiac Rehabilitation (CR) programs. Our aims are to describe the prevalence of extreme CV risk and its association with newly described CV risk factors. Design and method: We will evaluate 730 ACS patients enrolled in a CR program. Extreme CV risk will be defined as the presence of a previous (within 2 years) CV events in the patients clinical hystory. UA, LpA and inflammatory markers (interleukin-6 and -18, tumor necrosys factor alpha, C-reactive protein, calprotectin and osteoprotegerin) will be assessed in ACS/CCS patients with extreme CV risk and compared with ACS/CCS patients without extreme CV risk and two control groups: 1180 hypertensives and 765 healthy subjects. Results: Then we will assess the association between newly described CV risk factors and extreme CV risk with multivariable model and, for biomarkers selected as relevant, we will create two score system for the identification of extreme CV risk patients. The first one will use only clinical variables while the second one will introduce biochemical markers on top. The AUC values will be used to compare the diagnostic accuracy. Finally, by exome sequencing we ill both evaluate polygenic risk score ability to predict recurrent events and we will do mendellian randomization analysis on CV biomarkers Conclusions: Our study proposal was granted by the PNRR M6/C2 call. With this study we will give definitive data on extreme CV risk prevalence (probably higher than what actually believed) rising attention on this condition and leading cardiologist to better diagnose this condition and to carry out a more intensive treatment optimization that will leads to a reduction of future ACS recurrence.