People aged 70-100 years with elevated LDL-c are at high risk of MI and ASCVD

Elevated LDL cholesterol and increased risk of myocardial infarction and atherosclerotic cardiovascular disease in individuals aged 70–100 years: a contemporary primary prevention cohort

Literature - Mortensen MB & Nordestgaard BG., - Lancet. 2020 Nov 21;396(10263):1644-1652. doi: 10.1016/S0140-6736(20)32233-9.

Introduction and methods

LDL-c has been associated with development of atherosclerosis and is the primary treatment target in major guidelines [1,2]. Studies in historical cohorts have shown that the association of increased cholesterol with clinical events disappears in people above the age of 70 years [3-6]. However, these studies were done in cohorts enrolling patients up to 40-50 years ago. Since then, prevention and treatment of atherosclerotic cardiovascular disease (ASCVD) has changed, and life expectancy has increased [7]. This study examined the association of elevated LDL-c with MI and ASCVD risk in a contemporary primary prevention cohort.

Data for this study were obtained from 91,131 individuals enrolled between November 2003 and February 2016 in the Copenhagen General Population Study (CGPS). This cohort reflects the Danish general population aged 20-100 years. Participants and did not have ASCVD or diabetes at baseline and were not taking statins. Risk of MI (fatal and non-fatal) and ASCVD (MI, fatal coronary heart disease, and non-fatal or fatal ischemic stroke) per 1.0 mmol/L increase in LDL-c was determined in the overall population and stratified by age groups (20–49, 50–59, 60–69, 70–79, and 80–100 years). MI and ASCVD event rates per 1000 person-years were determined in individuals stratified by age groups and LDL-c levels (<2.0, 2.0–2.9, 3.0–3.9, 4.0–4.9, and ≥5.0 mmol/L). NNT in 5 years was calculated to estimate the potential effect of LDL-c lowering to prevent one event using moderate-intensity statin therapy in the different age groups (assuming a 30% relative risk reduction for MI and a 22% relative risk reduction of ASCVD). Mean follow-up was 7.7 (SD 3.2) years.

Main results

  • During follow-up, 1515 individuals had a MI and 3389 developed ASCVD. Risk of MI and ASCVD was raised per 1.0 mmol/L increase in LDL-c in the overall population (multivariable adjusted HR for MI 1.34, 95%CI 1.27-1.41; multivariable adjusted HR for ASCVD 1.16, 95%CI 1.12-1.21) and across all age groups.
  • MI and ASCVD event rates per 1000 person-years increased with higher LDL-c and older age, with highest event rates in individuals aged 80-100 years and LDL-c ≥5 mmol/L (13.2 MI events per 1000 person-years and 37.1 ASCVD events per 1000 person years).
  • MI events per 1000 person-years for every 1.0 mmol/L increase in LDL-c were 2.5 for individuals in the 80–100 years age group, 1.3 for those in the 70–79 years group, 0.7 for those in the 60–69 years group, 0.5 for those in the 50–59 years group, and 0.6 for those in the 20–49 years group.
  • ASCVD events per 1000 person-years for every 1.0 mmol/L increase in LDL-c were 4.0 for individuals in the 80–100 years age group, 1.5 for those in the 70–79 years group, 0.7 for those in the 60–69 years group, 0.5 for those in the 50–59 years group, and 0.6 for those in the 20–49 years group.
  • The NNT in 5 years to prevent one MI was 80 in the 80–100 years age group, 145 in the 70–79 years group, 261 in the 60–69 years group, 439 in the 50–59 years group, and 1107 in the 20–49 years group.
  • The NNT in 5 years to prevent one ACVD event event was 42 in the 80–100 years age group, 88 in the 70–79 years group, 164 in the 60–69 years group, 345 in the 50–59 years group, and 769 in the 20–49 years group.

Conclusion

This study in a contemporary general cohort showed that elevated LDL-c was associated with a higher absolute risk of MI and ASCVD in people aged 70–100 years compared to those aged 20-69 years. Moreover, the estimated NNT in 5 years to prevent one MI or ASCVD event was lower in people aged 70-100 years compared to younger individuals. These results are important for determining preventive strategies aimed at reducing MI and ASCVD events in older adults.

References

1. Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2019; 37: 2999.

2. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary— a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2019; 73: 3168–209.

3. Iversen A, Jensen JS, Scharling H, Schnohr P. Hypercholesterolaemia and risk of coronary heart disease in the elderly: impact of age: the Copenhagen City Heart Study. Eur J Intern Med 2009; 20: 139–44.

4. Gränsbo K, Almgren P, Nilsson PM, Hedblad B, Engström G, Melander O. Risk factor exposure in individuals free from cardiovascular disease differs according to age at first myocardial infarction. Eur Heart J 2016; 37: 1977–81.

5. Krumholz HM, Seeman TE, Merrill SS, et al. Lack of association between cholesterol and coronary heart disease mortality and morbidity and all-cause mortality in persons older than 70 years. JAMA 1994; 272: 1335–40.

6. Sniderman AD, Islam S, McQueen M, et al. Age and cardiovascular risk attributable to apolipoprotein B, low-density lipoprotein cholesterol or non-high-density lipoprotein

7. Kontis V, Bennett JE, Mathers CD, Li G, Foreman K, Ezzati M. Future life expectancy in 35 industrialised countries: projections with a Bayesian model ensemble. Lancet 2017; 389: 1323–35.

Watch the video with Prof. Nordestgaard about this study Find this article online at the Lancet

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