Conference Coverage

Cancer overtakes CVD as cause of death in high-income countries


 

REPORTING FROM ESC CONGRESS 2019

– Though cardiovascular disease still accounts for 40% of deaths around the world, cancer is eclipsing cardiovascular disease as a cause of mortality in high income nations, according to new data from a global prospective study.

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“Cancer deaths are becoming more frequent not because the rates of death from cancer are going up, but because we have decreased the deaths from cardiovascular disease,” said the study’s senior author, Salim Yusuf, MD, at the annual congress of the European Society of Cardiology.

A striking pattern emerged when cause of death was stratified by country income level, said fellow investigator Darryl P. Leong, MBBS, in presenting data regarding shifting global mortality patterns. Fully 55% of deaths in high-income nations were caused by cancer, compared with 30% in middle-income countries and 15% in low-income countries. In high-income countries, by contrast, cardiovascular disease (CVD) was the cause of death 23% of the time, while that figure was 42% and 43% for middle- and low-income countries, respectively.

Looking at the data slightly differently, the ratio of cardiovascular deaths to cancer deaths for high-income countries is 0.4; for middle-income countries, the ratio is 1.3, and “One is threefold more likely to die from cardiovascular disease as from cancer” in low-income countries, said Dr. Leong. Although the United States is not included in the PURE study, “recent data shows that some states in the U.S. also have higher cancer mortality than cardiovascular disease. This is a success story,” said Dr. Yusuf, since the shift is largely attributable to decreased mortality from CVD.

Dr. Leong and Dr. Yusuf each presented results from the PURE (Prospective Urban Rural Epidemiology) study, which has enrolled a total of 202,000 individuals from 27 countries on every inhabited continent but Australia. Follow-up data are available for 167,000 individuals in 21 countries. Canada, Russia, China, India, Brazil, and Chile are among the most populous national that are included. Their findings were published simultaneously in the Lancet with the congress presentations (2019 Sep 3; doi: 10.1016/S0140-6736(19)32008-2 and doi: 10.1016/S0140-6736(19)32007-0).

The INTERHEART risk score, an integrated cardiovascular risk score that uses non-laboratory values such as age, smoking status, family history, and comorbidities, was calculated for all participants. “We observed that the highest predicted cardiovascular risk is in high-income countries, and the lowest, in low-income countries,” said Dr. Leong, a cardiologist at McMaster University and the Population Health Research Institute, both in Hamilton, Ont.


Dr. Darryl Leong


Over the study period, 11,307 deaths occurred. Over 9,000 incident cardiovascular events were observed, as were over 5,000 new cancers.

“We have some interesting observations from these data,” said Dr. Leong. “Firstly, there is a gradient in the cardiovascular disease rates, moving from lowest in high-income countries – despite the fact that their INTERHEART risk score was highest – through to highest incident cardiovascular disease in low-income countries, despite their INTERHEART risk score being lowest.” This difference, said Dr. Leong, was driven by higher myocardial infarction rates in low-income countries and higher stroke rates in middle-income countries, when compared to high-income countries.

Once a participant was subject to one of the incident diseases, though, the patterns shifted. For CVD, cancer, chronic obstructive pulmonary disease, pneumonia, and injury, the likelihood of death within 1 year was highest in low-income countries – markedly higher, in the case of CVD. For all conditions, the one-year case-fatality rate after the occurrence of an incident disease was lowest in high-income countries.

“So we are seeing a new transition,” said Dr. Yusuf, the executive director of the Population Health Research Institute and Distinguished University Professor of Medicine, McMaster University, both in Hamilton, Ont. “The old transition was infectious diseases giving way to noncommunicable diseases. Now we are seeing a transition within noncommunicable diseases: In rich countries, cardiovascular disease is going down, perhaps due to better prevention, but I think even more importantly, due to better treatments.

“I want to hasten to add that the difference in risk between high-, middle-, and low-income countries in cardiovascular disease is not due to risk factors,” he went on. “Risk factors, if anything, are lower in the poor countries, compared to the higher-income countries.”

The shift away from cardiovascular disease mortality toward cancer mortality is also occurring in some countries that are in the upper tier of middle-income nations, including Chile, Argentina, Turkey, and Poland, said Dr. Yusuf, who presented data regarding the relative contributions of risk factors to cardiovascular disease and mortality.

Risk factors for cardiovascular disease in the PURE study were expressed by a measure called the population attributable fraction (PAF) that captures both the hazard ratio for a particular risk factor and the prevalence of the risk factor, explained Dr. Yusuf. “Hypertension, by far, was the biggest risk factor of cardiovascular disease globally,” he added, noting that the PAF for hypertension was over 20%. Hypertension far outstripped the next most significant risk factor, high non-HDL cholesterol, which had a PAF of less than 10%.

“This was a big surprise to us: Household pollution was a big factor,” said Dr. Yusuf, who later added that particulate matter from cooking, particularly with solid fuels such as wood or charcoal, was likely the source of much household air pollution, “a big problem in middle- and low-income countries.”

Tobacco usage is decreasing, as is its contribution to cardiovascular deaths, but other commonly cited culprits for cardiovascular disease were not significant contributors to cardiovascular disease in the PURE population.

“Abdominal obesity, and not BMI” contributes to cardiovascular risk. “BMI is not a good indicator of risk,” said Dr. Yusuf in a video interview. These results were presented separately at the congress.

“Grip strength is important; in fact, it is more important than low physical activity. People have focused on physical activity – how much you do. But strength seems to be more important…We haven’t focused on the importance of strength in the past.”

“Salt doesn’t figure in at all; salt has been exaggerated as a risk factor,” said Dr. Yusuf. “Diet needs to be rethought,” and conventional thinking challenged, he added, noting that consumption of full-fat dairy, nuts, and a moderate amount of meat all were protective among the PURE cohort.

Looking next at factors contributing to mortality in the global PURE population, low educational level had the highest attributable fraction of mortality of any single risk factor, at about 12%. “This has been ignored,” said Dr. Yusuf. “In most epidemiological studies, it’s been used as a covariate, or a stratifier,” rather than addressing low education itself as a risk factor, he said.

Tobacco use, low grip strength, and poor diet all had attributable fractions of just over 10%, said Dr. Yusuf, again noting that it wasn’t fat or meat consumption that made for the riskiest diet.

Overall, metabolic risk factors accounted for the largest fraction of risk of cardiovascular disease in the PURE population, with behavioral risk factors such as alcohol and tobacco use coming next. This held true across all income categories. However, in higher income nations where environmental factors and household air pollution are lower contributors to cardiovascular disease, metabolic and behavioral risk factors contributed more to cardiovascular disease risk.

Global differences in cardiovascular disease rates, stressed Dr. Yusuf, are not primarily attributable to metabolic risk factors. “The [World Health Organization] has focused on risk factors and has not focused on improved health care. Health care matters, and it matters in a big way.”

Adults aged 35-70 were recruited from 4 high-, 12 middle- and 5 low-income countries for PURE, and followed for a median 9.5 years. Cardiovascular disease and other health events salient to the study were documented both through direct contact and administrative record review, said Dr. Leong, and data about cardiovascular events and vital status were known for well over 90% of study participants.

Slightly less than half of participants were male, and over 108,000 participants were from middle income countries.

The PURE study was supported by the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada, the Ontaario Ministry of Health and Long-Term Care, Astra Zeneca, Boehringer Ingelheim, Sanofi-Aentis, Servier Laboratories, and Glaxo Smith Kline. The study also received additional support in individual participating countries. Dr. Yusuf and Dr. Leon reported that they had no relevant conflicts of interest.

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