Obesity and acute cardiovascular events

The prevalence of overweight and obesity has increased dramatically worldwide over the last decades. According to the World Health Organization, worldwide obesity has nearly tripled since 1975. In 2016, more than 1.9 billion adults, 18 years and older, were overweight. Of these over 650 million were obese. Prevalence is particularly high in the United States (US) with a high proportion of obesity (33% in both sexes) while South East Asia shows the lowest prevalence ranging between 1.7% obesity in Vietnam and 14% obesity in Malaysia. 1 Moreover, the prevalence of obesity in rural areas of China also increased rapidly between 1985 and 2014 (from 0.03 to 17.2% in boys and from 0.12 to 9.11% in girls).2 High body mass index (BMI) is associated with the development of cardiovascular risk factors such as hypertension, dyslipidemia, insulin resistance, and diabetes mellitus which are leading causes of death.3 The development of these comorbidities is proportionate to BMI and obesity is considered as an independent risk factor for cardiovascular events. Several studies have documented that a high BMI is significantly associated, in both men and women, with cardiovascular events such as angina, myocardial infarction, heart failure (HF) and sudden cardiac death (SCD).4 Although obesity is generally accepted as a risk factor for cardiovascular events, some studies showed that obesity could decrease mortality. This association seems blunted in some chronic condition with obese individuals presenting with a survival advantage over their counterparts, a phenomenon termed the ‘obesity paradox'.5 The use of BMI as a health risk phenotype has several limitations. BMI accounts for about two-thirds of individual variability in total adiposity. In spite of the high correlation of BMI with adiposity, a two to three-fold variation in visceral adiposity is observed at any given BMI, illustrating how BMI is not a specific index of abnormal fat accumulation. BMI does not accurately depict different components of body composition and is therefore unable to predict the prognostic effect of individual tissues (Figure 1).5,6 Oreopoulos et al. reported that BMI misclassified 41% of body fat status in patients with chronic heart failure (CHF). Directly measured body composition was also found to be more closely linked to indicate the prognosis in patients with CHF than BMI. A higher muscularity and/or lower adiposity were independently associated with advantageous prognostic factors in these patients. Using BMI as a proxy for adiposity may lead to incorrect assumptions about the relationship between obesity and outcomes in CHF and also cardiovascular events.7 BMI alone seems to present a U- or a J-shaped association with clinical outcomes and mortality.8 Other tools that could be used with BMI to refine an index of adiposity are waist circumference, waist-to-hip ratio, and waist-to-height ratio. Visceral adiposity can be measured accurately by computed tomography, magnetic resonance imaging, dual energy x-ray absorptiometry.9 Imaging cardiometabolic studies recently conducted in large cohort studies have shown that excess visceral adiposity accompanied by excess ectopic fat deposition such as excess heart, liver, and intrathoracic fat was significantly associated with cardiac and metabolic abnormalities, and that such a relationship was independent of the amount of total or subcutaneous adipose tissue.10 Illustration scheme of potential differences in body composition in individuals with identical body mass index (grey represents fat mass and black represents lean mass). Several potential factors concur to increase the risk of acute cardiovascular events including acute myocardial infarction, HF and SCD in obese patients. These factors are grouped into anatomical and functional factors. The anatomical factors include the cardiomyopathy leading for left ventricular diastolic dysfunction and left ventricular hypertrophy (LVH) while the functional factors include increased premature ventricular contractions, QT interval prolongation and dispersion, and heart rate variability.11 SCD is defined as unexpected, non-traumatic death occurring within 1 hour of the onset of new or worsening symptoms (witnessed arrest) or, if un-witnessed, within 24 hours of last being seen alive. SCD may be preceded by symptoms such as chest pain, dyspnea, palpitations, presyncope, and syncope but many individuals have no symptoms before the event. SCD is common with an annual incidence of 60 per 100,000 individuals. The incidence is higher in men (76 per 100,000) than in women (45 per 100,000). SCD incidence increases with age.12 The incidence of SCD in younger populations (<35 years) is lower than that in older individuals (0.5 per 100,000 in young American athletes to 13 per 100,000 recruit-years in US military recruits). Nearly 50% of people with SCD had no known previously diagnosed heart disorder.13 In a previous issue, Finocchiaro et al. report the result of SCD in the young (age ≤ 35 years) obese patients in term of clinical and pathological findings from a large national registry (1033 cases). They demonstrated that 20% (212 cases) of SCD in the young were obese (which is the same as the prevalence of obesity in the UK population under 35 years old) and obese individuals were younger than non-obese individuals (mean age 23 versus 27 years). These observational data suggested that the burden of SCD is not higher in obese individuals compared with individuals with a normal BMI. From this group, 87% were asymptomatic and the most common causes of SCD in both obese and non-obese is sudden arrhythmic death syndrome (SADS) (50% versus 60%). Moreover, obese individuals also had a higher prevalence of critical coronary artery diseases (CAD) (12% versus 3%).14 A previous study on SADS showed that the incidence of the Wolff–Parkinson–White (WPW) pattern in the population is 1–3 individuals per 1000. Approximately 65% of adolescents and 40% of individuals >30 years with the WPW pattern are asymptomatic. The mechanism of SCD in WPW is a rapid conduction of atrial flutter (AF) over the accessory connection that precipitates ventricular fibrillation (VF). Most episodes of SCD in the setting of WPW occur in children or adolescents and in those with symptoms. High-risk features for SCD in patients with a WPW pattern include age <30 years, male sex, history of AF, prior syncope, associated congenital or other heart disease, and familial WPW.15 From the study of Finocchiaro et al., they mention the association between obesity and electrical instability and prolonged QT interval but they do not show the result of history about WPW pattern. Another significant finding is that LVH was more frequently observed in obese young SCD victims compared with non-obese individuals. Massive LVH, defined as a wall thickness >30 mm, is another major risk marker for SCD. Massive LVH is present in approximately 10% of patients with hypertrophic cardiomyopathy (HCM) and is a stronger risk predictor in patients younger than 30 years of age. It has been suggested that in patients <30 years of age, the predominant risk of massive LVH is SCD, whereas in patients >60 years of age, the LVH risk is related to progressive HF.16 To prevent SCD in obese individuals, high physical activity will reduce cardiovascular disease risks (hazard ratio = 1.35). This emphasizes the importance of physical activity for everyone across all BMI strata.17 In summary, we learn from this study that obese individuals do not have a higher risk for SCD than individuals with a normal BMI. The most common etiology of SCD in individuals (obese and with a normal BMI) is SADS which comes from many pathophysiologic mechanisms. However, further study is needed to stratify the obesity group in detail not only in terms of BMI > 35 kg/m2. Moreover, BMI alone may not have the correct answer regarding SCD in obese individuals, and lean body weight may be the best parameter for this field of study. Finally, the risk associated with obesity, particularly SCD, was attenuated in individuals with high physical activity levels. The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The author(s) received no financial support for the research, authorship, and/or publication of this article.