New PURE Insights: CVD Deaths Dip in Rich Nations Amid Risk-Factor Surprises

PARIS, France—Cardiovascular disease remains the leading cause of death worldwide, but cancer has now overtaken heart disease as the biggest killer in Canada, Sweden, Saudi Arabia, and the United Arab Emirates, the four high-income countries included as part of the Prospective Urban Rural Epidemiology (PURE) study.

Presenting the latest results from PURE during the Hot Line session at the European Society of Cardiology (ESC) Congress 2019, Darryl Leong, MBBS, PhD (Population Health Research Institute, Hamilton, Canada), said that while cardiovascular disease mortality may have declined in richer countries, at least among those they studied, it is still the leading cause of death in countries that are middle income (Argentina, Brazil, Chile, China, Columbia, Iran, Malaysia, Palestine, Philippines, Poland, Turkey, and South Africa) and low income (Bangladesh, India, Pakistan, Tanzania, and Zimbabwe).

“One is approximately twice as likely to die from cancer in high-income countries in PURE as opposed to dying from cardiovascular causes,” said Leong, who presented the findings on the analysis looking into global variations in disease, hospital admissions, and death. In contrast, there was a slight excess of cardiovascular disease mortality relative to cancer deaths in middle-income countries, but individuals in low-income countries were threefold more likely to die from cardiovascular disease than cancer.

Salim Yusuf, MD (McMaster University/Population Health Research Institute), the principal investigator of PURE, said there is a transition underway within noncommunicable disease given that cardiovascular disease is no longer the biggest threat in wealthy countries. “Perhaps this may be because of better prevention, but I think more importantly it may be because of better treatment,” said Yusuf. The overall reduction in cardiovascular mortality relative to cancer in high-income countries “is a success story,” he added, noting that the same pattern is even being seen in some US states, although that nation was not included in PURE.

Higher INTERHEART Risk Score, Lower CVD Death

The new analysis, which was published September 3, 2019, in the Lancet, focused on 162,534 individuals aged 35 to 70 years enrolled between 2005 and 2016 and followed for a median of 9.5 years. During follow-up, 11,307 participants died, 9,329 developed cardiovascular disease, and 4,386 developed cancer. Cardiovascular disease occurred more frequently in low-income countries (7.1 cases per 1,000 person-years) and middle-income countries (6.8 cases per 1,000 person-years) than in high-income countries (4.3 cases per 1,000 patient years).   

Globally, 40% and 26% of all deaths were attributable to cardiovascular disease and cancer, respectively. Respiratory illnesses, injury, and infection were the other leading causes of death. In high-income countries, however, 23% of deaths were the result of cardiovascular disease compared with 55% of deaths from cancer. In middle- and low-income countries, cardiovascular disease was the leading cause of mortality, responsible for 42% and 43% of all deaths, respectively.

Speaking during a morning press conference at ESC, Yusuf stressed that the difference in mortality from cardiovascular disease in high-income countries was not due to better risk factor control. In fact, the INTERHEART risk score, a measure of propensity to cardiovascular disease that incorporates health behaviors and risk factors, was higher among those from high-income countries.

“The differences in cardiovascular rates are not primarily due to risk factors,” said Yusuf. “The [World Health Organization] is focused on risk factors and is not focused on improved healthcare and healthcare matters in a big way.” While there are conventional risk factors responsible for CVD mortality, Yusuf, who has been critical of salt and dietary recommendations for years, said there is a need for new thinking around food. “Diet needs to be rethought, [and] not the conventional thinking,” he said.  

Kim Williams Sr, MD (Rush University Medical Center, Chicago, IL), a past president of the American College of Cardiology, pointed out that the PURE analysis is based on selective high-income countries, and excludes the United States, Australia, and Great Britain, among others. In the US, cardiovascular disease remains the leading cause of death—while cardiovascular disease mortality rates have declined, the increase in metabolic risk factors, such obesity and diabetes, has halted or even reversed that decline.

“It really comes down to nutrition,” he told TCTMD. “People make nutrition choices more on habit, culture, and television than they do based on health. We need to get that message out there. I’m never happy at how well we market our guidelines to tell people they can make intelligent food choices that can save their life.”

Modifiable Risk Factors in PURE

In a second study, which also was presented during the Hot Line session and published in the Lancet, the PURE investigators conducted a detailed analysis of modifiable risk factors, cardiovascular disease, and mortality; these data were presented by Yusuf. Globally, more than 70% of cardiovascular disease cases were attributable to a small number of modifiable characteristics, particularly metabolic risk factors.

“Hypertension was by far the biggest risk factor of cardiovascular disease globally,” said Yusuf. Following hypertension, he added, are a number of risk factors responsible for cardiovascular disease as assessed by the population attributable fraction (PAF). These include high non-HDL cholesterol levels, household pollution, tobacco use, poor diet, low education, abdominal obesity, diabetes mellitus, and low grip strength.

“Household pollution was a big surprise to us,” said Yusuf. “This is a big problem in the low- to middle-income countries, but not so in high-income countries.”

In high-income countries, the top five risk factors for cardiovascular disease were high non-HDL cholesterol, tobacco use, hypertension, diabetes, and abdominal obesity, which are largely metabolic risk factors. In middle-income countries, the five biggest drivers of heart disease were hypertension, low education, tobacco use, household air pollution, and abdominal obesity. In low-income countries, hypertension, non-HDL cholesterol, household pollution, diabetes, and poor diet were largely responsible for cardiovascular disease.

Yusuf said that while metabolic risk factors play a large role in cardiovascular disease, household air pollution and low education have been overlooked. Williams agreed, telling TCTMD that he has observed the importance of education in cardiovascular health as he treats patients in clinical practice.

“Education is huge,” said Williams. “In the African-American community that I take care of, there is a big difference between the population that’s educated and the population that isn’t. We’ve seen that for decades. Education doesn’t absolve you from having cardiovascular disease, but the outcomes are better. Why is that? Is it access to care, or better income? But having a graduate degree has actually been shown to improve cardiovascular mortality.”

The PURE analysis, he added, “really doubles down” on the importance of education, and it may be worthwhile for physicians to encourage younger patients to complete further schooling.

Nonetheless, Williams pointed out that the two biggest risk factors responsible for cardiovascular disease remain high blood pressure (PAF 22.5% globally) and high non-HDL cholesterol (PAF 8.1 globally), both of which can be substantially reduced with adherence to a healthy lifestyle and increased physical activity. In fact, Williams pointed to several studies presented at the ESC meeting showing the benefits of low systolic blood pressure and LDL cholesterol, including a recent genetic analysis looking at lifetime exposure to low levels.

With respect to mortality in PURE, behavioral and metabolic risk factors, along with low education and low grip strength, all contribute to mortality to roughly the same degree. Low education, tobacco use, low grip strength, poor diet, and hypertension were the five risk factors most associated with mortality, with the PAFs ranging from 12.5% for low education to 8.8% for hypertension. Grip strength, which may be a marker for frailty or possibly nutrition, is also not given enough attention.