Heart Failure Interplays With Economics Across the World: PURE Data

Heart failure (HF) incidence varies across the globe, perhaps due to economic factors, a new population-based analysis suggests. Individuals living in countries at higher levels of economic development have a higher rate of diagnosis, while patients with known HF who reside in countries at the lower end of the economic spectrum are more likely to die.

Across more than 172,000 individuals followed for a median of 15 years in the global PURE study, the standardized rate of incident HF was 0.39 per 1,000 person-years. When stratified by wealth, countries with upper middle and high income levels had the highest rates at 0.58 and 0.36 per 1,000 person-years, respectively, while lower-middle- and low-income countries had the lowest at 0.34 and 0.26 per 1,000 person-years.

Although several studies have examined HF prevalence, “when it comes to incidence of heart failure, there really is very little data,” lead author Isabelle Johansson Bartolini, PhD (Population Health Research Institute, Hamilton, Canada and Karolinska Institutet, Stockholm, Sweden), told TCTMD. “Even in high-income countries, there is little comparable data, but when you look at a global perspective, there really [has been] nothing up until now.”

She called the PURE study a “golden opportunity” to dig into regional discrepancies that might inform potential solutions to improving outcomes.

The relatively low incidence of HF in lower-income countries likely doesn’t reflect a lower HF burden, Johansson Bartolini said, but rather suggests “that we may be missing cases.” Together with their finding that hypertension was likely the cause behind one-quarter of incident cases, “[it] means that there are low-hanging fruits that we can attack with region-specific strategies,” she continued. “The implication would be that we need prevention strategies to be focused differently in different settings.”

Commenting on the study for TCTMD, Ambarish Pandey, MD (University of Texas Southwestern Medical Center, Dallas), who recently presented the FUND-HF trial showing financial incentives improve medication adherence in HF with reduced ejection fraction, called the PURE data “really important.”

The wide variety of individuals included is the study’s biggest strength, he said, adding that the low incidence/high mortality paradox “suggests that patients in low-income countries are not getting as much access to care for diagnosis and they’re often presenting late, with more severe disease, and they’re dying in their first or index presentation.”

PURE Data

The study, published online recently in JACC, included 172,653 individuals from 25 countries representing eight geographic regions with follow-up data in the PURE study.

Classifying countries by gross national income per capita according to the World Bank, high-income countries (HICs) included Canada, Saudi Arabia, Sweden, and the United Arab Emirates; upper middle-income countries (UMICs) included Argentina, Brazil, Chile, Ecuador, Kazakhstan, Malaysia, Poland, Russia, South Africa, and Turkey; lower middle-income countries (LMICs) were China, Colombia, Kyrgyzstan, Iran, the West Bank, and the Philippines; and lower-income countries (LICs) were Bangladesh, India, Pakistan, Tanzania, and Zimbabwe. Most study participants (40%) resided in LMIC, 28% in UMICs, 22% in LICs, and 10% in HICs.

Over a median follow-up of 14.9 years, 1,587 people in total had a first unrefuted HF event, including 40% classified as definite, 20% as probable, and 40% as possible HF. About one-third of these cases were due to ischemic heart disease and one-third to hypertension.

Compared to those without HF, individuals with a HF event were older (mean 58.6 vs 50.3 years), had less education (54.1% vs 41.6% with primary school or less), more commonly male (50.4% vs 41.1%), more often overweight (28.1% vs 18.1% with body mass index ≥ 30 kg/m²), and more often smokers (42.9% vs 31.5%). They also had more hypertension (67.7% vs 38.7%), ischemic heart disease (14.6% vs 3.4%), diabetes (25.1% vs 10.7%), and depression (13.9% vs 11.6%).

On multivariate analysis, ischemic heart disease (HR 2.76; 95% CI 2.33-3.28), hypertension (HR 1.91; 95% CI 1.65-2.20), diabetes (HR 1.89; 95% CI 1.63-2.20), and tobacco use (HR 1.67; 95% CI 1.41-1.99) were independently associated with incident HF.

The rate of fatal first HF events was lowest in North America (12%) as well as Europe and Central Asia (17% each), with the highest rates observed in South Asia (63%) and sub-Saharan Africa (63%). Death rates after a first HF presentation adjusted for age and sex were 36% at 30 days, 43% at 1 year, and 54% at 5 years. The 30-day mortality rate was highest in LICs (61%) and lowest in HICs (9%; P < 0.0001). Similar findings were observed at 1 year (68% vs 15%) and 5 years (77% vs 28%; P < 0.0001 for both).

‘A Call to Action’

Controlling hypertension and improving earlier detection are likely to have the biggest payoffs across the world in reducing the incidence of HF, although how to do so is likely to differ based on country and region, according to Johansson Bartolini.

“If you have access to preventive care strategies, then we will be able to prevent people from actually developing heart failure, which is really the end stage of heart disease, and instead reduce suffering and prolong life,” she said. “These are things that we do in higher-income countries, but in lower-income settings there is a lot more to do to achieve that.”

As much as she hopes clinicians and the general public will pay attention to her work, Johansson Bartolini said politicians need to take heed as well. “We need to also increase knowledge about hypertension, about ischemic heart disease, about risk factors that eventually lead to severe heart disease,” she said. “It’s very important to do these kind of studies to understand the burden and to understand where we can take action.”

Next, Johansson Bartolini would like to see more studies delve into HF data in low-income settings “to understand better the pattern that we see with low incidence rates and high case fatality rates, which we don’t really believe [means there is] a lower burden, . . . and if there are policy initiatives that can actually improve the situation.”

Pandey said he found it especially interesting that UMICs seem to fall into an “epidemiologic transition zone.” Patients there are living long, but with a high burden of risk factors leading to a high number of HF cases, yet they lack prevention strategies and guideline-directed medical therapy, which leads to substantial case-fatality rates as well.  

The role that hypertension plays in incident HF here is consistent with the literature, he said, adding that this is another “call to action to improve hypertension control.”

Going forward, “there is a need to better understand the drivers of adverse outcomes,” Pandey said. “I would also like to see the pattern of use of guideline-directed medical therapy and then drivers or predictors of adverse outcomes and mortality in this patient population.”