Elsevier

The Lancet

Volume 390, Issue 10107, 4–10 November 2017, Pages 2050-2062
The Lancet

Articles
Associations of fats and carbohydrate intake with cardiovascular disease and mortality in 18 countries from five continents (PURE): a prospective cohort study

https://doi.org/10.1016/S0140-6736(17)32252-3Get rights and content

Summary

Background

The relationship between macronutrients and cardiovascular disease and mortality is controversial. Most available data are from European and North American populations where nutrition excess is more likely, so their applicability to other populations is unclear.

Methods

The Prospective Urban Rural Epidemiology (PURE) study is a large, epidemiological cohort study of individuals aged 35–70 years (enrolled between Jan 1, 2003, and March 31, 2013) in 18 countries with a median follow-up of 7·4 years (IQR 5·3–9·3). Dietary intake of 135 335 individuals was recorded using validated food frequency questionnaires. The primary outcomes were total mortality and major cardiovascular events (fatal cardiovascular disease, non-fatal myocardial infarction, stroke, and heart failure). Secondary outcomes were all myocardial infarctions, stroke, cardiovascular disease mortality, and non-cardiovascular disease mortality. Participants were categorised into quintiles of nutrient intake (carbohydrate, fats, and protein) based on percentage of energy provided by nutrients. We assessed the associations between consumption of carbohydrate, total fat, and each type of fat with cardiovascular disease and total mortality. We calculated hazard ratios (HRs) using a multivariable Cox frailty model with random intercepts to account for centre clustering.

Findings

During follow-up, we documented 5796 deaths and 4784 major cardiovascular disease events. Higher carbohydrate intake was associated with an increased risk of total mortality (highest [quintile 5] vs lowest quintile [quintile 1] category, HR 1·28 [95% CI 1·12–1·46], ptrend=0·0001) but not with the risk of cardiovascular disease or cardiovascular disease mortality. Intake of total fat and each type of fat was associated with lower risk of total mortality (quintile 5 vs quintile 1, total fat: HR 0·77 [95% CI 0·67–0·87], ptrend<0·0001; saturated fat, HR 0·86 [0·76–0·99], ptrend=0·0088; monounsaturated fat: HR 0·81 [0·71–0·92], ptrend<0·0001; and polyunsaturated fat: HR 0·80 [0·71–0·89], ptrend<0·0001). Higher saturated fat intake was associated with lower risk of stroke (quintile 5 vs quintile 1, HR 0·79 [95% CI 0·64–0·98], ptrend=0·0498). Total fat and saturated and unsaturated fats were not significantly associated with risk of myocardial infarction or cardiovascular disease mortality.

Interpretation

High carbohydrate intake was associated with higher risk of total mortality, whereas total fat and individual types of fat were related to lower total mortality. Total fat and types of fat were not associated with cardiovascular disease, myocardial infarction, or cardiovascular disease mortality, whereas saturated fat had an inverse association with stroke. Global dietary guidelines should be reconsidered in light of these findings.

Funding

Full funding sources listed at the end of the paper (see Acknowledgments).

Introduction

Cardiovascular disease is a global epidemic with 80% of the burden of disease in low-income and middle-income countries.1 Diet is one of the most important modifiable risk factors for cardiovascular disease and other non-communicable diseases and current guidelines recommend a low-fat diet (<30% of energy) and limiting saturated fatty acids to less than 10% of energy intake by replacing them with unsaturated fatty acids.2 However, recommendations on lowering saturated fatty acids are largely based on one ecological study3 and observational studies done in European and North American countries such as Finland, where the intake of saturated fatty acids (about 20% of total energy intake) and cardiovascular disease mortality were both very high.4 Furthermore, dietary recommendations are based on the assumption of a linear association between saturated fatty acid intake and LDL cholesterol, and then the association between LDL cholesterol and cardiovascular disease events. However, this assumption does not consider the effect of saturated fatty acids on other lipoproteins (eg, HDL cholesterol), ratio of total cholesterol to HDL cholesterol, or on apolipoproteins (which could be a better marker of cardiovascular disease risk)5, 6 and blood pressure, which also affect the risk of cardiovascular disease.7

Research in context

Evidence before this study

We did a systematic search in PubMed for relevant articles published between Jan 1, 1960, and May 1, 2017, restricted to the English language. Our search terms included “carbohydrate”, “total fat”, “saturated fatty acid”, “monounsaturated fatty acid”, “polyunsaturated fatty acid”, “total mortality”, and “cardiovascular disease”. We searched published articles by title and abstract to identify relevant studies. We also hand-searched reference lists of eligible studies. We considered studies if they evaluated association between macronutrient intake and total mortality or cardiovascular disease. The studies cited in this report are not an exhaustive list of existing research. Existing evidence on the associations of fats and carbohydrate intake with cardiovascular disease and mortality are mainly from North America and Europe.

Added value of this study

Current guidelines recommend a low fat diet (<30% of energy) and limiting saturated fatty acids to less than 10% of energy intake by replacing them with unsaturated fatty acids. The recommendation is based on findings from some North American and European countries where nutrition excess is of concern. It is not clear whether this can be extrapolated to other countries where undernutrition is common. Moreover, North American and European populations consume a lower carbohydrate diet than populations elsewhere where most people consume very high carbohydrate diets mainly from refined sources. Consistent with most data, but in contrast to dietary guidelines, we found fats, including saturated fatty acids, are not harmful and diets high in carbohydrate have adverse effects on total mortality. We did not observe any detrimental effect of higher fat intake on cardiovascular events. Our data across 18 countries adds to the large and growing body of evidence that increased fats are not associated with higher cardiovascular disease or mortality.

Implications of all the available evidence

Removing current restrictions on fat intake but limiting carbohydrate intake (when high) might improve health. Dietary guidelines might need to be reconsidered in light of consistent findings from the present study, especially in countries outside of Europe and North America.

Recently, several meta-analyses of randomised trials and prospective cohort studies8, 9, 10 and ecological studies,11 largely done in European and North American countries, showed either no association or a lower risk between saturated fatty acid consumption with total mortality and cardiovascular disease events.12, 13 The uncertainty regarding the effect of saturated fatty acids on clinical outcomes in part might be due to the fact that most observational cohort studies have been done in high-income countries8, 9 where saturated fatty acid intake is within a limited range (about 7–15% of energy). Furthermore, it is not known whether findings obtained from European and North American countries where nutritional excess is more common, can be extrapolated to other regions of the world where nutritional inadequacy might be more common. The Prospective Urban Rural Epidemiology (PURE) study provides a unique opportunity to study the impact of diet on total mortality and cardiovascular disease in diverse settings, such as those where overnutrition is common and where undernutrition is of greater concern. In this study, our primary aim was to assess the association of fats (total, saturated fatty acids, and unsaturated fats) and carbohydrate with total mortality and cardiovascular disease events. The secondary aim was to examine associations between these nutrients and myocardial infarction, stroke, cardiovascular disease mortality, and non-cardiovascular disease mortality.

Section snippets

Study design and participants

The design and methods of the PURE study have been described previously.1, 14, 15, 16 PURE recruitment occurred between Jan 1, 2003, and March 31, 2013, and included individuals aged 35–70 years from 18 low-income, middle-income, and high-income countries on five continents. We aimed to include populations that varied by socioeconomic factors while ensuring feasibility of long-term follow-up when selecting the participating countries. We included three high-income (Canada, Sweden, and United

Results

During a median follow-up of 7·4 years (IQR 5·3–9·3), 5796 individuals died and 4784 had a major cardiovascular disease event (2143 myocardial infarctions and 2234 strokes). 1649 died due to cardiovascular disease and 3809 died due to non-cardiovascular disease. There were 338 deaths due to injury, which were not included in non-cardiovascular disease mortality because these were considered to be unlikely to be associated with diet. Among non-cardiovascular disease mortality, in all regions

Discussion

In this large prospective cohort study from 18 countries in five continents, we found that high carbohydrate intake (more than about 60% of energy) was associated with an adverse impact on total mortality and non-cardiovascular disease mortality. By contrast, higher fat intake was associated with lower risk of total mortality, non-cardiovascular disease mortality, and stroke. Furthermore, higher intakes of individual types of fat were associated with lower total mortality, non-cardiovascular

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