Elevated LDL-c associated with high absolute risk of MI and ASCVD in people aged 70–100 years
Elevated LDL cholesterol and increased risk of myocardial infarction and atherosclerotic cardiovascular disease in individuals aged 70–100 years: a contemporary primary prevention cohort
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 . 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.
- 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.
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.