ESC/EAS statin eligibility criteria in primary prevention should include very high TG levels
Unmet need for primary prevention in individuals with hypertriglyceridaemia not eligible for statin therapy according to European Society of Cardiology/European Atherosclerosis Society guidelines: a contemporary population-based study
Literature - Madsen CM, Varbo A, Nordestgaard BG. - Eur Heart J 2017; published online ahead of printBackground
Genetic studies and RCTs have demonstrated a causal association between high TG concentrations and triglyceride-rich lipoproteins and atherosclerotic CV disease (ASCVD), which cannot be explained by the inverse association between TGs and HDL-C [1]. However, no studies have assessed the impact of TG-lowering on ASCVD risk in primary prevention, and in the 2016 ESC/EAS guidelines, no definite recommendations are given on initiation of lipid-lowering therapy based on high TG levels [2].
In this analysis of the Copenhagen General Population Study (CGPS), the absolute risk of ASCVD was determined in 58 547 individuals who were divided into subgroups according to statin eligibility and TG concentrations. CGPS participants aged 40–65 years, without ASCVD, DM, or statin use at baseline, were included in the analysis and followed for a median of 8 years, and participants on statins, were evaluated for their statin eligibility, based on the 2016 ESC/EAS guidelines [2]. Individuals with very high risk and LDL-C ≥ 1.8 mmol/L (70 mg/dL) or with high risk and LDL-C ≥ 2.6 mmol/L (100 mg/dL) were defined as definite statin eligible. For comparison, individuals were also assigned to definite statin eligibility based on the 2013 ACC/AHA guidelines and the 2016 USPSTF recommendations [3,4](results not shown here).
ASCVD risk was calculated based on age, gender, smoking status, SBP, DBP, TC, LDL-C, HDL-C, and chronic kidney disease, according to guidelines [5]. The SCORE low-risk equations were used without HDL-C, but HDL-C levels were incorporated for sensitivity analyses. The endpoints were MI, and the composite MACE, including CV death, non-fatal MI, unstable angina pectoris and stroke.
Main results
- During 456 057 person-years of follow-up, the overall incidence rate of MACE was 3.9 (95% CI: 3.7–4.1) per 1000 person-years (PY), and the incidence of MI was 1.6 (1.5–1.7) per 1000 PY.
- According to 2016 EAS/ESC criteria, 14% of individuals were definite statin eligible. Among individuals who were not definite statin eligible, 8% had TG levels >3mmol/L (264mg/dL).
- The 2016 ESC/EAS guideline to treat individuals with very high risk and TGs >2.3mmol/L (202mg/dL) pharmacologically, would apply to only 209 individuals (0.4%) not already definite statin eligible by the LDL-C criteria.
- The incidence rates of MACE and MI increased with increasing concentrations of TGs. Individuals who were not definite statin eligible and had TGs <1.0mmol/L (88mg/dL) had the lowest incidence rates of MACE (2.2; 95% CI: 1.9–2.5) and MI (0.6; 95% CI: 0.5–0.8) per 1000 PY.
- Individuals with TGs of 4.0–4.99mmol/L (352–439mg/dL) had the highest incidence rates of MACE (7.9; 95% CI: 6.0–10.3) and MI (4.3; 95% CI: 3.0–6.2) per 1000 PY, which were similar to the rates for definite statin eligible individuals. The estimated 10-year risks of MACE and MI showed a similar pattern as for the incidence rates.
- Using a cut-off value of 3.0mmol/L (264mg/dL) in individuals who were not definite statin eligible showed that those with TGs ≥ 3mmol/L have similar risks of MACE and MI to definite statin eligible individuals (P=0.75 and P= 0.42), and higher risks than in those with TGs <3.0mmol/L (P< 0.0001 for both endpoints).
Conclusion
In a large population-based study, high TG levels identified individuals at high risk of ASCVD, who would not be definite eligible for statin treatment according to the 2016 ESC/EAS guidelines. These results suggest that guidelines on statin eligibility in primary prevention might have to be expanded to individuals with hypertriglyceridemia.
References
1. Keene D, Price C, Shun-Shin MJ, et al. Effect on cardiovascular risk of high density lipoprotein targeted drug treatments niacin, fibrates, and CETP inhibitors: meta-analysis of randomised controlled trials including 117,411 patients. BMJ 2014;349:g4379.
2. Catapano AL, Graham I, De Backer G, et al; Authors/Task Force Members; Additional Contributor. 2016 ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J 2016;37:2999–3058.
3. Stone NJ, Robinson JG, Lichtenstein AH, et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:2889–2934.
4. Bibbins-Domingo K, Grossman DC, Curry SJ, et al; Force USPST. Statin use for the primary prevention of cardiovascular disease in adults: US Preventive Services Task Force Recommendation Statement. JAMA 2016;316:1997–2007.
5. Nordestgaard BG, Langsted A, Mora S, et al; European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Joint Consensus initiative. Fasting is not routinely required for determination of a lipid profile: clinical and laboratory implications including flagging at desirable concentration cut-points-a joint consensus statement from the European Atherosclerosis Society and European Federation of Clinical Chemistry and Laboratory Medicine. Eur Heart J 2016;37:1944–1958.
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