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Chapter Summary

This chapter discusses the pathophysiology and treatment of cardiometabolic disease and obesity. Insulin resistance is at the core of the pathophysiology of cardiometabolic disease and can give rise to metabolic syndrome, prediabetes, and non-alcoholic fatty liver disease (NAFLD) (see Fuster and Hurst’s Central Illustration). Patients with insulin resistance, metabolic syndrome, and/or prediabetes have accelerated atherogenesis and increased risk for cardiovascular disease (CVD). Prediabetes and NAFLD can progress to type 2 diabetes and non-alcoholic steatohepatitis (NASH), respectively; these conditions further amplify the progression of vascular disease and risk of CVD events. Obesity can exacerbate insulin resistance and promote cardiometabolic disease progression, but it can also exist independent of cardiometabolic disease. In the prevention and treatment of cardiometabolic disease, intervention should be early and encompass metabolic and vascular outcomes. Healthy meal plans, aerobic and resistance exercise, and aggressive surveillance and management of CVD risk factors are all warranted. A chronic care model for cardiometabolic disease should be an integral component of health-care systems.

INTRODUCTION: CARDIOMETABOLIC DISEASE AND CARDIOVASCULAR DISEASE RISK

The term cardiometabolic disease (CMD) indicates that there is a common pathophysiological process that results in both metabolic and cardiovascular disease. This chapter will provide the clinical and mechanistic justifications for the term and contextualize cardiovascular disease (CVD) as an end-stage manifestation of this chronic disease process, thus providing opportunities for primordial, primary, secondary, and tertiary prevention and treatment. At the core of CMD is the insulin-resistant state that gives rise to clinically identifiable conditions at high risk for future CVD events—namely, metabolic syndrome (MetS), prediabetes, and non-alcoholic fatty liver disease (NAFLD). Obesity can exacerbate insulin resistance and impel this disease progression. Thus, insulin resistance, prediabetes, and MetS all represent states of accelerated atherogenesis and mark patients at higher risk for CVD.1–3 Furthermore, once metabolic disease becomes overt, with the development of type 2 diabetes (T2D) and/or non-alcoholic steatohepatitis (NASH), there is further amplification of vascular disease progression and risk of CVD events. Within the context of CMD, treatment and prevention must concomitantly encompass both metabolic and vascular outcomes. Given the increasing burden of patient suffering and social costs exacted by this nexus of diseases interrelated via CMD pathophysiology, it becomes imperative to intervene early to halt CMD progression.

The acceleration of atherosclerosis by the insulin-resistant state is analogous to the impact of elevated low-density lipoprotein cholesterol (LDL-C) or cigarette smoking, which are emphasized as major targets for the primary prevention of CVD using a variety of dietary, behavioral, and pharmacological interventions. There is, perhaps, less of a concerted effort for prevention focused on the insulin-resistant state. The lowering of LDL-C levels in statin cardiovascular outcome trials results in an average risk reduction of approximately 30%, leaving a preponderant degree of “residual” risk.4 Insulin resistance may account for the bulk of this residual risk and may be responsible for ...

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