The elderly still stand to benefit from lipid-lowering therapy

High LDL cholesterol (LDL-C) levels are associated with the greatest absolute risk of myocardial infarction (MI) and atherosclerotic cardiovascular disease (ASCVD) in elderly people aged 70–100 years than other age groups in a contemporary primary prevention cohort — indicating that LDL-C is an important risk factor for CVD in the elderly, in contrast to historical studies.

The role of LDL-C in ischaemic heart disease in elderly people (aged >70 years) has been controversial — with previous studies showing mixed results of no or little association between elevated LDL-C and increased MI risk in this population. However, these data were derived from historical cohorts enrolling patients four to five decades ago, when prevention and treatment of ASCVD differed from contemporary practice. Guideline recommendations for statins were also lacking in this age group due to scarce clinical evidence.  

“[In our contemporary primary prevention cohort], high LDL-C in apparently healthy people older than 70 years is not a benign finding because it is associated with a substantially higher risk of developing MI and ASCVD,” according to the researchers.

“By lowering LDL cholesterol in healthy individuals aged 70–100 years, the potential for preventing MI and ASCVD is huge, and at a substantially lower number needed to treat when compared with those aged 20–69 years,” they reported. “Our data should guide decision making about whether older individuals will benefit from statin therapy.”

The contemporary cohort

Subjects in the analysis were 91,131 individuals aged 20–100 years identified from the Copenhagen General Population Study (CGPS). Those who were free of ASCVD and diabetes at baseline and who were not treated with statins were included in the analysis. [Lancet 2020;396:1644-1652]

For every 1.0 mmol/L increase in LDL-C levels, the risk of MI increased across all age groups, with a 34 percent increase in the overall population (adjusted hazard ratio [HR], 1.34, 95 percent confidence interval [CI], 1.27–1.41). Similarly, the risk of ASCVD also rose with across all age groups with every 1.0 mmol/L increase in LDL-C levels, with a HR of 1.16 (95 percent CI, 1.12–1.21) in the overall population.

For both MI and ASCVD, the increase in absolute risk with rising LDL-C levels was particularly pronounced in participants aged 70–100 years, as these age groups experienced a higher event rates than the younger age groups.

For every 1.0 mmol/L increase in LDL-C levels, MI events per 1,000 person-years rose to 2.5 and 1.3 for the age groups of 80–100 years and 70–79 years, respectively, compared with 0.7, 0.5, and 0.6 for those aged 60–69, 50–59, and 20–49 years, respectively. The corresponding events per 1,000 person-years for ASCVD were 4.0 and 1.5, respectively, for the older age groups and 0.7, 0.5, and 0.6, respectively, for the younger age groups, with each 1.0 mmol/L increase in LDL-C levels.

When comparing elderly individuals with elevated LDL-C (≥5.0 mmol/L) vs those with optimal levels (<3.0 mmol/L), the risk of MI was almost tripled in the age group of 80–100 years (HR, 2.99, 95 percent CI, 1.71–5.23) and doubled in the age group of 70–79 years (HR, 1.82, 95 percent CI, 1.20–2.77).  

Assuming all people were treated with moderate-intensity statin, the 5-year NNT* to prevent one event of MI or ASCVD was lowest for those aged 70–100 years — suggesting that the cumulative burden of LDL-C was highest in the elderly and that this group would likely benefit from preventive strategies such as statin therapy.

“Individuals aged 70–100 years are, therefore, likely to gain a substantially greater 5-year benefit from LDL cholesterol-lowering than are younger people,” said the researchers. “Our results suggest that statin therapy in people aged 70–100 years with elevated LDL-C will help many older people live additional years free of MI and ASCVD before the end of life.”

“These data are of importance for primary prevention strategies and guidelines aimed at managing and reducing ASCVD in the growing older population,” they highlighted. 

*NNT: number needed to treat