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Management of Severe and Moderate Hypercholesterolemia in Young Women and Men
JAMA Cardiology  (IF14.676),  Pub Date : 2021-11-15, DOI: 10.1001/jamacardio.2021.4983
Shauna L. Newton, Alexander P. Hoffmann, Zhi Yu, Sara Haidermota, Pradeep Natarajan, Michael C. Honigberg

Cardiovascular guidelines advise statin therapy for adults aged 20 to 75 years with low-density lipoprotein cholesterol (LDL-C) levels of 190 mg/dL or greater, with a goal of lowering LDL-C by at least 50%.1 Early-life accumulation of cholesterol exposure increases future cardiovascular risk independent of midlife2 and total cumulative cholesterol exposure,3,4 highlighting the importance of LDL-C management in young adults. However, contemporary real-world management of hypercholesterolemia in young adults is not well described.

Using clinical registry data from 7 Mass General Brigham hospitals and affiliated practices, we isolated 2 cohorts of patients with cholesterol testing on 2 or more occasions who were 20 to 39 years old at the time of a qualifying LDL-C value between 2005 and 2018: cohort 1 included individuals with an LDL-C value of 190 mg/dL or greater, and cohort 2 included those with an LDL-C value between 160 and less than 190 mg/dL. All follow-up LDL-C values were extracted through December 31, 2019. Prescriptions for lipid-lowering therapy (LLT), including statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors, were additionally extracted. Primary end points were a 50% reduction in LDL-C for cohort 1 and a 30% reduction in cohort 2. The Massachusetts General Hospital institutional review board approved these analyses as non–human subjects research with waived informed consent.

Among 17 591 individuals meeting inclusion criteria, 5438 (30.9%) had severe hypercholesterolemia (cohort 1; 37.9% female; mean age, 32.6 [SD, 5.1] years at qualifying LDL-C measurement), and 12 513 (71.1%) had moderate hypercholesterolemia (cohort 2; 39.8% female; mean age, 32.7 [SD, 5.1] years). In cohort 1, over a median follow-up of 7.8 (IQR, 4.5-11.4) years, 1638 individuals (30.1%) achieved at least a 50% LDL-C reduction (27.2% of women vs 31.9% of men; P < .001) (Figure). Younger individuals were less likely to achieve a 50% LDL-C reduction (eg, age 20-24 years, 24.9%; age 35-39 years, 33.0%; P < .001 for trend) (Table). Mean LDL-C at last follow-up was 152.9 (SD, 51.2) mg/dL, and 1271 patients (23.4%) had a last LDL-C value of 190 mg/dL or greater. Overall, LLT was prescribed for 48.5% of individuals, including 77.5% who achieved at least 50% LDL-C reduction vs 36.0% who did not (P < .001); LLT was less frequently prescribed for women vs men (43.7% vs 51.5%; P < .001).