UC Irvine

Cardiovascular disease (CVD) stands as the predominant cause of mortality on a global scale, with diabetes mellitus (DM) emerging as a prominent risk factor for CVD. Notably, adults afflicted by DM face a nearly twofold increased risk of CVD-related mortality compared to their non-DM counterparts. The present dissertation undertakes the task of formulating pre- ventive strategies for CVD within the DM patient population. The first chapter of this study endeavors to ascertain the residual risk of CVD stemming from hypertriglyceridemia (HTG) in the DM population, drawing data from the National Health Nutrition and Examination Survey (NHANES) spanning the years 2007 to 2014. Interestingly, it is observed that despite the implementation of first-line lipid-lowering therapy involving statin usage and optimal low- density lipoprotein cholesterol (LDL-C) control, approximately one-fifth of this population continues to exhibit HTG. Additionally, three-quarters of DM patients possess a moderate to high 10-year risk for CVD. The second chapter aims to assess the potential impact of two novel DM medications, namely liraglutide (glucagon-like peptide-1 receptor agonists (GLP-1 RAs)) (Chapter 2) and empagliflozin (sodium-glucose cotransporter 2 inhibitor (SGLT-2i)) (Chapter 3), on CVD prevention. The evaluation is conducted in terms of the preventive capacity for CVD events while on treatment, utilizing the NAHNES database. Followingix the meticulous application of key inclusion and exclusion criteria derived from corresponding clinical trials, an estimated 4.2 million and 1.86 million US DM patients are deemed eligi- ble for these treatments, respectively. Moreover, approximately 21,209 and 12,066 major cardiovascular events, comprising a composite outcome of cardiovascular death, myocardial infarction, and stroke, could be averted annually, respectively. The forth chapter endeav- ors to explore the impact of multifactorial risk control—encompassing body mass index, blood glucose, blood pressure, blood lipid levels, physical activity, nicotine exposure, sleep health, and dietary patterns—on the relative risk of CVD development among DM patients based on the UK Biobank database. Notably, a strikingly low percentage of only 2.2% of DM patients demonstrate ideal control over at least six of the above risk factors, and this achievement is associated with an 84% lower risk of incident CVD when compared to individ- uals without any risk factor control. The combined findings of the four chapters underscore the paramount importance of adopting an integrative approach to CVD prevention, partic- ularly in the context of DM patients. The insights gained from this research endeavor hold significant implications for shaping comprehensive strategies aimed at mitigating CVD risks and enhancing patient outcomes within this vulnerable population.