Obesity and cardiovascular disease: revisiting an old relationship

Highlights

• Obesity is closely linked to CVD

• This relationship is direct and indirect

• Adipose tissue localization and metabolism play a crucial role

• Weight loss confers important risk reduction

Abstract

A wealth of clinical and epidemiological evidence has linked obesity to a broad spectrum of cardiovascular diseases (CVD) including coronary heart disease, heart failure, hypertension, stroke, atrial fibrillation and sudden cardiac death. Obesity can increase CVD morbidity and mortality directly and indirectly. Direct effects are mediated by obesity-induced structural and functional adaptations of the cardiovascular system to accommodate excess body weight, as well as by adipokine effects on inflammation and vascular homeostasis. Indirect effects are mediated by co-existing CVD risk factors such as insulin resistance, hyperglycemia, hypertension and dyslipidemia. Adipose tissue (AT) quality and functionality are more relevant aspects for cardiometabolic risk than its total amount. The consequences of maladaptive AT expansion in obesity are local and systemic: the local include inflammation, hypoxia, dysregulated adipokine secretion and impaired mitochondrial function; the systemic comprise insulin resistance, abnormal glucose/lipid metabolism, hypertension, a pro-inflammatory and pro-thrombotic state and endothelial dysfunction, all of which provide linking mechanisms for the association between obesity and CVD. The present narrative review summarizes the major pathophysiological links between obesity and CVD (traditional and novel concepts), analyses the heterogeneity of obesity-related cardiometabolic consequences, and provides an overview of the cardiovascular impact of weight loss interventions.

Introduction

According to World Health Organization (WHO) estimates, over half of the global adult population is overweight or obese [1]. In many regions of the world, obesity prevalence is still increasing rapidly, and if the current trends continue, it will reach globally 18% in men and surpass 21% in women by 2025, imposing a heavy burden upon individuals, societies and health care systems [2]. Based on these data, obesity has been justifiably characterized as a modern global epidemic disease [3].

A wealth of clinical and epidemiological evidence has linked obesity to a broad spectrum of cardiovascular diseases (CVD) including coronary heart disease (CHD), heart failure (HF), hypertension, cerebrovascular disease, atrial fibrillation (AF), ventricular arrhythmias and sudden cardiac death (SCD). Obesity has been also linked to obstructive sleep apnea and other hypoventilation syndromes, which adversely affect cardiovascular function [4].

Obesity can increase CVD morbidity and mortality directly and indirectly. Direct effects are mediated by obesity-induced structural and functional adaptations of the cardiovascular system to accommodate excess body weight, as well as by adipokine effects on inflammation and vascular homeostasis, leading to a pro-inflammatory and pro-thrombotic milieu. Indirect effects are mediated by concomitant CVD risk factors such as insulin resistance, type 2 diabetes mellitus (T2DM), visceral adiposity, hypertension and dyslipidemia [5].

Body mass index (BMI), defined as body weight in kg divided by height in meters squared, is the most widely used anthropometric index to define obesity [6]. Although simple and reproducible, it has been heavily criticized for its intrinsic weakness to discriminate between fat and lean body mass and its inability to account for different patterns of body composition and regional fat distribution [7]. These limitations partly explain why concepts like the obesity paradox and the metabolically healthy obese (MHO) phenotype have raised scepticism and fuelled controversies in obesity research [8,9]. In support of the problematic use of BMI as an obesity index, various large-scale epidemiological studies including the case-control INTERHEART study, have shown that central adiposity is more strongly related to CVD risk than total adiposity expressed by BMI [[10], [11], [12]]. It has been therefore argued that anthropometric indices of central fat distribution such as waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and imaging measurements of visceral fat by computed tomography (CT) or magnetic resonance imaging (MRI), should be assessed on top of BMI due to their better predictive power for CVD risk [13].

It has been further suggested that adipose tissue (AT) integrity and functionality are more relevant aspects for cardiometabolic risk determination than its total amount [14]. AT can regulate the fate of excess dietary lipids and determine whether metabolic homeostasis will be maintained or a state of low-grade systemic inflammation and insulin resistance will develop with deleterious cardiometabolic consequences. AT may also orchestrate interactions with other vital organs such as the brain, liver, skeletal muscle, heart and blood vessels within the framework of an inter-tissue metabolic cross-talk [15]. The consequences of AT expansion are both local and systemic: the local include inflammation [16], hypoxia [17], fibrosis [18], dysregulated adipokine secretion [19], and impaired mitochondrial function [20]; the systemic comprise insulin resistance, abnormal glucose and lipid metabolism, hypertension, a pro-inflammatory and pro-thrombotic state and endothelial dysfunction, all of which provide linking mechanisms between obesity and CVD [21].

The present narrative review summarizes the major pathophysiological links between obesity and CVD, analyses the heterogeneity of obesity-related cardiometabolic consequences, and provides an overview of the cardiovascular impact of weight loss interventions.