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The recent epidemic of obesity has led to an increasing incidence of the cardiometabolic syndrome defined by the NCEP ATP III guidelines as a cluster of abdominal obesity, low HDL, high triglycerides, HTN, and impaired fasting glucose. Obesity predisposes the body to a state of inflammation, insulin resistance, and hyperinsulinemia, and individuals with the metabolic syndrome are at increased risk for developing CAD, stroke, PVD, CKD, and T2DM. There are various mechanisms by which these complications of the metabolic syndrome occur, and activation of systemic and local renin angiotensin aldosterone system (RAAS) and resultant oxidative stress in different organ systems is probably the most important one. Finally, based on recent trials, the approach toward management of the metabolic syndrome is usually multifactorial and multiagent and studies are still being performed to assess the efficacy of newer drugs.

The prevalence of the cardiometabolic syndrome (CMS), a cluster of cardiovascular disease (CVD) risk factors which include central obesity, dysglycemia, atherogenic dyslipidemia, hypertension (hypertension), and microalbuminuria (MAU), has increased. Obesity largely drives the dramatic increase in the incidence and prevalence of the CMS worldwide. Recently there has been increasing interest in the association between CMS, obesity, and chronic kidney disease (CKD), which is multifactorial and includes genetic as well as environmental factors. Obesity, hypertension, and dysglycemia are strongly associated with a systemic chronic low-grade inflammation, inappropriate activation of the renin–angiotensin–aldosterone system (RAAS), and increased oxidative stress. The link between RAAS activation and oxidative stress has been a subject of great interest over the past several years.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in women in the USA. Women with diabetes are at a greater risk of CVD than men with diabetes. In this chapter we review the various mechanisms by which hyperglycemia potentiates this increased CVD risk, including coagulation abnormalities as well as endothelial dysfunction. Where applicable, sex-specific differences in these mechanisms are highlighted. Finally, the impact and burden of diabetes on CVD as well as screening for CVD in women are discussed.

Renin angiotensin aldosterone system (RAAS) activation plays an essential role in the development of cardiovascular disease (CVD). Multiple pathophysiologic processes are able to activate RAAS, among which hypertension, obesity, diabetes mellitus 2, and chronic kidney disease deserve special attention, because they are the main contributors to CVD. Adding to the well-known effects of RAAS overactivity on the vasculature and water and electrolyte balance, current evidence links abnormal activation of the RAAS to increased production of reactive oxygen species (ROS) and oxidative stress. This association is mediated at least partially through interaction of angiotensin II (Ang II) with its receptor angiotensin receptor 1 (AT1R) in cardiovascular tissue, and subsequent activation of the nicotinamide adenine dinucleotide phosphate (NADPH) enzymatic complex, which finally leads to increased ROS production. This resulting state of enhanced oxidative stress contributes largely to generalized atherosclerosis and finally to CVD. The generation of animal models of increased RAAS and Ang II expression, in particular the Ren2 rodent model, provides important opportunities to better characterize the relationship between this system and the production of ROS. This chapter describes methods to evaluate, characterize, and quantify the activity of the RAAS and NADPH oxidase, as well as the production of ROS production in animal model of RAAS.