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13th March 2023
Elevated plasma levels of the artificial sweetener erythritol, in patients undergoing cardiac risk assessment is associated with an increased 3-year risk of a major cardiovascular event according to the findings of an analysis by an international research group.
Low calorie artificial sweeteners are widely found in food and drinks and some of the most thoroughly tested and evaluated of all food additives. However, there is some evidence to suggest a significant association between intake of artificially sweetened soda consumption and obesity and to an increased risk of all-cause mortality. Nevertheless, a 2017 scoping review was unable to offer conclusive evidence for either beneficial or harmful effects of artificial sweeteners on several adverse health outcomes.
Erythritol is a sugar alcohol and commonly used as a sugar substitute and there is actually data indicating how acute consumption improves small vessel endothelial function whereas chronic use reduces central aortic stiffness. In contrast, other work suggests an association between erythritol and incident diabetes. Despite these findings, little is known about the relationship between erythritol and both cardiovascular disease and atherothrombotic complications and this was the purpose of the current study. Researchers initially measured plasma levels of the artificial sweetener among US patients undergoing elective diagnostic cardiac evaluation (which they referred to as the ‘discovery cohort’) and then compared the findings with results obtained from a second US and European cohort also undergoing cardiac evaluation.
Erythritol levels and incident MACE
In the discovery cohort with 1,157 patients, circulating levels of erythritol, were associated with incident (3-year) risk for major adverse cardiovascular events, including death or nonfatal myocardial infarction or stroke (adjusted hazard ratio, aHR = 2.95, 95% CI 1.70 – 5.12, p < 0.001) when comparing the highest vs lowest plasma erythritol levels. Subsequent analysis in the US cohort also confirmed an increased risk of MACE (aHR = 1.80, 95% CI 1.18 – 2.77, p = 0.007) as well as the European cohort (aHR = 2.21, 95% CI 1.20 – 4.07, p = 0.010). In fact, for every 1 μM increase in plasma erythritol levels, there was a 21% and 16% increase in the adjusted HR for MACE in the US and European validation cohorts respectively (p < 0.001 and p = 0.005).
In trying to better understand the potential mechanisms behind these effects, the researchers also found that erythritol heightened platelet reactivity in vitro and thrombosis formation in vivo. Finally, in a small study with 8 healthy subjects, ingestion of the sweetener produced elevated plasma levels which remained high for hours after ingestion and remained substantially elevated for over two days.
Although recognising a limitation of the study in that the data were obtained from patients with a high prevalence of cardiovascular disease and with traditional risk factors, the authors concluded that erythritol is both associated with incident MACE risk and fosters enhanced thrombosis.
Witkowski M et al. The artificial sweetener erythritol and cardiovascular event risk. Nat Med 2023
1st November 2021
A high triglyceride-HDL cholesterol ratio (TG-HDL-C) and a high computed tomography angiography (CTA) score have been found to be independently associated with worse cardiac outcomes in a group of patients with stable angina. These are the findings of a multinational, prospective, observational study undertaken across seven European countries by a team from the Institute of Clinical Physiology, Pisa, Italy. Traditionally, for patients with known or suspected coronary artery disease, a standard lipid profile is conducted measuring total cholesterol, high density lipoprotein (HLD), low density lipoprotein (LDL) and triglycerides. While much attention has focused in treatment guidelines on a lowering of LDL cholesterol levels as means reducing cardiovascular risk, in recent years, emerging evidence suggests that a higher TG-HDL-C ratio is correlated with an increased risk of major CV events, even in the presence of low LDL cholesterol.
Nevertheless, whether the cardiovascular profile characterised by a high TG-HDL-C is associated with adverse events over the longer term is unknown and was the objective of the work undertaken by the Italian team. The study population came from the EVINICI cohort, in which patients with stable chest pain or equivalent symptoms and an intermediate risk of coronary artery disease, were referred for computed tomography and a smaller cohort were invited for a follow-up scan. For all participants, data on cardiovascular risk factors such as age, gender, family history of coronary heart disease, smoking status, co-morbidities etc were collected. In addition, measurement of cholesterol sub-fractions (e.g., HDL-C) and individual’s triglycerides levels were undertaken at baseline and after being followed up. The researchers set the primary outcome as a combination of major adverse events (AEs), including all-cause death and non-fatal myocardial infarction.
A total of 355 individuals with a mean age of 60 years (59% male) were included in the analysis. The overall baseline mean triglyceride:HDL cholesterol ratio was 2.78 and the mean CTA score 11.53. In addition, the majority of individuals had atypical chest pain (60%) or typical angina (25%).
A total of 154 patients were followed up over median duration of 4.5 years, during which time, 25 patients (7%) experienced a major AE including 8 deaths and 17 non-fatal myocardial infarctions. While over the follow-up period, mean LDL cholesterol levels were significantly reduced (106 vs 94, p = 0.0004), there was a significant increase in the TG-HDL-C ratio (2.49 vs 2.96, p = 0.0027), as well as an increase in mean CTA scores (11.02 vs 12.94, p < 0.0001). Using multivariate analysis, higher TG-HDL-C ratios were an independent predictor of prognosis (adjusted Hazard ratio, aHR = 2.51, 95% CI 1.09 – 5.81, p = 0.03) as was the CTA score (aHR = 1.06, 95% CI 1.03 – 1.11, p = 0.0006).
Commenting on these findings, the authors suggested that the TG-HDL-C ratio could be used as is a simple method to identify those individuals with a substantial residual coronary risk not tackled by current treatments. They concluded that a high triglyceride and a low HDL-C levels are associated with coronary artery disease related outcomes independent of both LDL-C and treatments.
Csselli C et al. Triglycerides and low HDL cholesterol predict coronary heart disease risk in patients with stable angina. Sci Rep 2021