1. In individuals aged 70-100 years, there was a significantly increased risk of myocardial infarction and atherosclerotic cardiovascular disease for every 1.0 mmol/L increase in LDL cholesterol.
2. Individuals aged 80-100 years were found to have the lowest number needed to treat in 5 years to prevent one myocardial infarction.
Evidence Rating Level: 2 (Good)
Study Rundown: Atherosclerotic cardiovascular disease (ASCVD) is a major driver of morbidity and mortality around the world. Levels of LDL cholesterol are widely acknowledged as an important risk factor in the development of ASCVD and targeting healthy LDL values is a mainstay in the management of cardiovascular conditions. Although many guidelines currently recommend the treatment of elevated LDL levels, most do not recommend doing so beyond the age of 70 years. This primary prevention cohort study monitored LDL levels and incidence of ASCVD and myocardial infarction (MI) in individuals aged 20-100 years to determine if an association existed beyond the age of 70 years. Overall, elevated LDL cholesterol was strongly associated with incidence of ASCVD and MI in all age groups, particularly those aged 70-100 years. Amongst individuals with LDL>5.0mmol/L, MI risk was four times higher in those aged 80-100 versus those aged 20-69. The number needed to treat (NNT) in 5 years to prevent one MI was lowest for individuals aged 80-100 years and highest in those aged 20-49 years. A strength of this study is its large sample size and robust follow-up rate. An important limitation, however, is the exclusive inclusion of individuals of white European (Danish) descent as incidence of cardiovascular disease may vary across different ethnicities. Likewise, findings must be interpreted in the context that ASCVD is nearly ubiquitous and found in a large portion of patients seen in hospital and clinic; thus, these results would be less applicable.
In-Depth [prospective cohort]: This primary prevention cohort study enrolled 91 131 individuals aged 20-100 years from the Danish general population as part of the Copenhagen General Population Study (CGPS) (n=3188, 80-100 years old). Participants were of a white European ethnic background of Danish descent and did not have a pre-existing history of ASCVD, diabetes, or statin use. The primary endpoints of this study were incidence of MI and ASCVD. Overall, for every 1.0 mmol/L increase in LDL cholesterol, there was an increased risk of MI (Hazard ratio [HR] = 1.34, 95% CI 1.27-1.41) and ASCVD (HR = 1.16, 95% CI 1.12-1.21) across all age groups. Compared to those with LDL levels < 3 mmol/L, individuals aged 80-100 years with LDL levels ≥ 5.0 mmol/L had a nearly 3- and 2-fold increased risk for MI (HR = 2.99, 95% CI 1.71-5.23) and ASCVD (HR = 1.90, 1.27-2.83), respectively. In individuals with an LDL ≥ 5.0 mmol/L, the MI event rate was nearly four times greater in those aged 80-100 years compared to those aged 20-69 years (multivariable adjusted HR = 3.7, 95% CI 1.6-8.8). NNT in 5 years was based on a relative risk reduction of 30% for MI and 22% for ASCVD per 1mmol/L LDL level drop using moderate-intensity statin therapy. Overall, NNT for MI risk reduction was 80 in ages 80-100, 145 for 70-79, 261 for 60-69 and 439 for 50-59. NNT for ASCVD risk reduction was 42 in ages 80-100, 88 for 70-79, 164 for 60-69 and 345 for 50-59. Taken together, these findings produce strong support for the consideration of LDL reduction for ASCVD and MI risk prevention in individuals aged 70-100 years.
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