Asian HF patients commonly lean, yet diabetic

Among Asian patients with heart failure (HF), those who have HFpEF* with a lean diabetic phenotype have the worst prognosis among the five phenotypes identified in Asians which include patients with HFrEF**, according to data from the Asian-HF registry presented at the ESC Asia Congress 2019.

This finding stands in contrast with the global trend of a worse prognosis with HFrEF vs HFpEF in previous studies which involved a predominantly Caucasian population. Also, Asian HF patients tend to be lean compared with their Western counterparts.

Lean, yet diabetic

“These patients are very thin and yet, [they are] predominantly diabetic … very unique to this region,” said Professor Carolyn Lam from Duke-National University of Singapore, who noted that this phenotype is especially prevalent among patients in Singapore, Hong Kong, and Malaysia. 

The lean diabetic phenotype was associated with the highest incidence of the primary composite outcome of all-cause mortality or hospitalization for HF at 1 year than the other four phenotypes—the young, the ischaemic, elderly with atrial fibrillation (AF), and the metabolic phenotype (p<0.001). The young and the ischaemic phenotypes were predominantly seen in patients with HFrEF. [PLoS Med 2018;15:e1002541]

In addition, the lean diabetic phenotype had the worst quality of life (QoL) along with more severe HF signs and symptoms compared with the other phenotypes (p<0.001 for all).

Waist-to-height ratio is telling

To further characterize the association between the lean diabetic phenotype and the primary composite outcome, 286 patients with bioelectrical impedance data available from the Asian-HF cohort were categorized into four groups based on their BMI and waist-to-height ratio (WHtR), which measures the distribution of body fat.

“Outcome is better with increasing BMI, as previously known as the obesity paradox; but with increasing WHtR there is worse outcome,” said Lam, indicating that there is an opposing relationship between BMI and WHtR for the composite outcome.

The lean diabetic phenotype had the worst outcome among the four profiles (both high BMI and WHtR, both low BMI and WHtR, high BMI but low WHtR, and low BMI but high WHtR). Compared with the group with both high BMI and WHtR (typical of the metabolic phenotype), the group with low BMI but high WHtR (typical of the lean diabetic phenotype) had almost double the risk of the primary composite outcome (hazard ratio, 1.9, 95 percent confidence interval, 1.2–3.2).

A defining feature of the low BMI but high WHtR group is a lean profile with accumulation of fat at the trunk region, explained Lam. “Each standard deviation increase in WHtR was associated with 0.44 unit increase in percentage trunk fat (p<0.05) after adjusting for BMI, sex, and age,” she reported.

Finding an explanation 

“What is happening in the heart [of these HF patients] with not much macrovascular disease in terms of coronary artery disease? So, could this be a manifestation of microvascular disease?” Lam raised.  

Indeed, Lam and team found that HFpEF may be a manifestation of systemic microvascular disease in diabetes. Among 2,800 Asian patients prospectively enrolled in Asian-HF, diabetic microvascular disease is more prevalent in patients with HFpEF than those with HFrEF. [Diabetes Care 2019;42:1792–1799]

Diabetic microvascular disease is also associated with a greater left ventricular remodelling and more impaired QoL in patients with HFpEF.  

“It’s very clear [in] HFpEF, with more microvascular beds involved such as retinopathy, nephropathy, and neuropathy … there is a greater odds of having HFpEF,” Lam stated.

Why is this important?

“For management of diabetes, the minute you find evidence of microvascular disease such as even proteinuria in a patient, one should already be looking at the heart for diastolic dysfunction,” Lam urged.

“To diabetologists, the message is that diabetic heart disease is not only about macrovascular heart disease such as myocardial infarction, it includes microvascular disease and HFpEF rather than HFrEF,” she added.