Regional adiposity and heart failure with preserved ejection fraction

Abstract

The role of obesity in the pathogenesis of heart failure (HF), and in particular HF with preserved ejection fraction (HFpEF), has drawn significant attention in recent years. The prevalence of both obesity and HFpEF has increased worldwide over the past decades and when present concomitantly suggests an obese-HFpEF phenotype. Anthropometrics, including body mass index, waist circumference, and waist-to-hip ratio, are associated with incident HFpEF. However, the cardiovascular effects of obesity may actually be driven by the distribution of fat, which can accumulate in the epicardial, visceral, and subcutaneous compartments. Regional fat can be quantified using non-invasive imaging techniques, including computed tomography, magnetic resonance imaging, and dual-energy X-ray absorptiometry. Regional variations in fat accumulation are associated with different HFpEF risk profiles, whereby higher epicardial and visceral fat have a much stronger association with HFpEF risk compared with elevated subcutaneous fat. Thus, regional adiposity may serve a pivotal role in the pathophysiology of HFpEF contributing to decreased cardiopulmonary fitness, impaired left ventricular compliance, upregulation of local and systemic inflammation, promotion of neurohormonal dysregulation, and increased intra-abdominal pressure and vascular congestion. Strategies to reduce total and regional adiposity have shown promise, including intensive exercise, dieting, and bariatric surgery programmes, but few studies have focused on HFpEF-related outcomes among obese. Further understanding the role these variable fat depots play in the progression of HFpEF and HFpEF-related hospitalizations may provide therapeutic targets in treating the obese-HFpEF phenotype.

Waist to height ratio is associated with an increased risk of mortality in Chinese patients with heart failure with preserved ejection fraction

“…Abdominal adipose deposition has a close relationship with systemic inflammation [ 5 ] and is also a prominent feature of HFpEF [ 6 , 7 ]. Several studies have demonstrated that abdominal obesity may predict adverse consequences and a greater risk of all-cause mortality in patients with HFpEF [ 8 , 9 ].…”

PDE9 Inhibition Activates PPARα to Stimulate Mitochondrial Fat Metabolism and Reduce Cardiometabolic Syndrome

“…The pandemic has already had a major impact on global health as obesity increases the risks for diabetes, dyslipidemia, non-alcoholic fatty liver disease, inflammatory syndromes, heart failure, and hypertension, all components of cardiometabolic syndrome (CMS) (1, 3, 4) . Human studies have shown abdominal (visceral) obesity is most pathogenic (5) , whereas metabolically active adipose tissue known as brown fat appears to be protective (6) . Obesity-related disorders exhibit a sexual dimorphism as premenopausal women are relatively protected largely due to estrogen (7, 8) , yet after menopause when visceral fat increases, so do the risks for developing CMS (9, 10) .…”

Heart failure development in obesity: underlying risk factors and mechanistic pathways

“…Also, a somewhat low frequency of smoking in the total study group (21%) and a moderate alcohol consumption among study participants (alcohol abuse was an exclusion criterion in the SOS study) may have contributed to the lack of association between these risk factors and incident HF. Conversely, abdominal obesity was associated with incident HF in both unadjusted and adjusted analysis, supporting an active role of visceral fat with respect to the development of HF, in particular HFpEF 50 …”

“…Conversely, abdominal obesity was associated with incident HF in both unadjusted and adjusted analysis, supporting an active role of visceral fat with respect to the development of HF, in particular HFpEF. 50 Of notice is the relationship between increasing circulating levels of free thyroxine within normal reference values and incident HF among subjects with obesity in both unadjusted and adjusted analysis. This relationship, which has received little attention previously, 6 was apparent in the total study group and among women, in particular.…”