LOS ANGELES – When it comes to understanding the impact of diet on cardiovascular disease, mounting evidence suggests that a high carbohydrate diet is associated with a higher risk of mortality, while consumption of fats, including saturated and unsaturated fats, is associated with a lower risk of mortality.
Ronald M. Krauss, MD, said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “There are various categories of evidence that we all consider. Randomized clinical trials are the most robust, but, in this field, there are few and, of these, a number have been subject to criticism. Observational cohort studies provide much of the data on which we base our dietary recommendations. This is a problem, because dietary information can be flawed, it’s challenging to adjust for all the covariates in an observational trial, and you can’t determine causation.”
Dr. Krauss, senior scientist and director of atherosclerosis research at Children’s Hospital Oakland (Calif.) Research Institute, emphasized that current dietary recommendations are often not based on food context. Meta-analyses may be used to make dietary recommendations, “but you have to be careful,” he said. “There is quite a bit of subjectivity in the criteria used to select the studies. Finally, there is individual variability in dietary effects. You lose that when you do statistical analysis in large study populations.”
An analysis of prospective observational cohort studies over the past several years showed that there is no significant effect of saturated fat intake on all-cause mortality, cardiovascular disease (CVD), coronary heart disease (CHD), ischemic stroke, or type 2 diabetes mellitus (BMJ. 2015 Aug 12. doi: 10.1136/bmj.h3978). However, it found that trans fats are associated with all-cause mortality, total CHD, and CHD mortality. A more recent meta-analysis of randomized, controlled trials of saturated fat intake and coronary heart disease in the past 5 years yielded similar findings.
“Saturated fat intake per se is not associated with all-cause mortality, CVD, CHD, stroke, or type 2 diabetes,” said Dr. Krauss, who was an author of a recent analysis on dietary fat and cardiometabolic health (BMJ. 2018 Jun 13. doi: 10.1136/bmj.k2139). “The replacement nutrient is important, but there has been controversy as to whether replacing saturated fat with n-6 (omega-6) polyunsaturated fatty acids reduced CHD events, CHD mortality, or total mortality.”
Other research has demonstrated differences in the relationship of saturated fat from meat sources vs. that from dairy sources. An analysis of 5,209 subjects who participated in the Multi-Ethnic Study of Atherosclerosis (MESA) study over 10 years found that a higher intake of dairy saturated fat was associated with lower CVD risk (Am J Clin Nutr. 2012;96[2]:397-404). In contrast, a higher intake of saturated fat from meat was associated with greater CVD risk.
In what Dr. Krauss said is the most extensive prospective cohort study of its kind to date, researchers led by Mahshid Dehghan, PhD, collected self-reported dietary data from 135,335 people aged 35-70 years in 18 countries, and grouped them according to the amount of carbohydrate, fat, and protein they consumed (Lancet. 2017 Aug 29. doi: 10.1016/S0140-6736[17]32252-3). Outcomes for the study, known as PURE, were major CVD and total mortality.
Over a median follow-up of 7.4 years, the researchers documented 5,796 deaths and 4,784 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, hazard ratio 1.28; P = .0001) but not with the risk of CVD or CVD 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, P less than .0001; saturated fat, HR, 0.86, P = .0088; monounsaturated fat: HR 0.81, P less than .0001; and polyunsaturated fat: HR 0.80, P less than .0001). Higher saturated fat intake was associated with lower risk of stroke (quintile 5 vs. quintile 1, HR, 0.79; P = .0498). Total fat and saturated and unsaturated fats were not significantly associated with risk of myocardial infarction or cardiovascular disease mortality.
“The fat intake becomes a protective factor, while carbohydrates are the bad guys,” said Dr. Krauss, who also holds faculty positions at the University of California, San Francisco, and the University of California, Berkeley. He acknowledged certain limitations of PURE, including the fact that the random measurement used in the assessment of diet may dilute real associations, that high carbohydrate and low-fat diets may be a proxy for poverty, and that data on vegetable oil use were not included.
Dr. Krauss went on to note that work from other studies has shown that the Apo B/Apo A-1 ratio and its association with small – but not large – LDL particles is a stronger marker than is LDL cholesterol for predicting dietary effects on CVD risk (Lancet. 2004;364[9438]:937-52 and Arterioscler Thromb Vasc Biol. 2014;34[5]:1069-77). “These risk measures can be improved by lowering dietary carbohydrates, and not by lowering saturated fats,” he said.
Dr. Krauss disclosed that he has received grants from the National Institutes of Health and Dairy Management Inc. He is a member of the scientific advisory board for Virta Health and DayTwo and holds a patent related to lipoprotein particle analysis.