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Familial Resemblance in Low-Density Lipoprotein Cholesterol Response to Statins in the Danish Population.

ABSTRACT: Background Change in low-density lipoprotein cholesterol (LDL-C) level after statin initiation varies widely among individuals, and in part may be because of factors shared by family members. Methods and Results We used the Danish national registers to identify 89 006 individuals who initiated statins between 2008 and 2018 and had LDL-C measured immediately before and after the start of treatment. Among these, we identified 5148 first-degree relatives and 3198 spouses. We decomposed the variation in attained LDL-C level after statin initiation by applying a mixed-effect model with 5 variance components (inter-family and inter-individual variance in pre-statin LDL-C level, inter-family and inter-individual variance in statin response, and residual variance). Results were presented as a percentage of the total variance explained by the different variance components. We found that half of the variation in attained LDL-C level after statin initiation consisted of variance in statin response, approximately one third of variance in pre-statin LDL-C level, and the remaining 10% to 15% of residual variance. While the inter-individual variance in statin response accounted for almost half of the LDL-C variation in both cohorts, the inter-family variance in statin response accounted for 3.3% among first-degree relatives and for 6.0% among spouses. Conclusions Individual factors account for most of the variation in LDL-C level after statin initiation; factors affecting statin response common within spouses and first-degree relatives account for a similar share of variation. These results suggest a modest influence of shared genetics and shared familial environment on statin response.

SUBMITTER: Corn G

PROVIDER: S-EPMC9238694 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Low-density lipoprotein cholesterol (LDL-C) is an important modifiable risk factor for atherosclerotic cardiovascular disease. It is unclear whether the percentage LDL-C lowering with pharmacotherapies differs on the basis of baseline LDL-C levels. To evaluate the association between baseline LDL-C levels and the percentage LDL-C reduction with a statin, ezetimibe, and a PCSK9 inhibitor. This secondary exploratory study analyzed data from 3 randomized placebo-controlled clinical trials (Aggrastat to Zocor-Thrombolysis in Myocardial Infarction 21 [A to Z-TIMI 21], Improved Reduction of Outcomes: Vytorin Efficacy International Trial [IMPROVE-IT], and Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk [FOURIER]) of lipid-lowering therapies (statin, ezetimibe, and a PCSK9 inhibitor) and included participants with atherosclerotic cardiovascular disease. Analyses took place form April to October 2020. In A to Z-TIMI 21, 1:1 randomization to simvastatin, 40 mg, daily for 30 days followed by 80 mg daily thereafter vs placebo for 4 months followed by simvastatin, 20 mg, daily thereafter. In IMPROVE-IT, 1:1 randomization to ezetimibe, 10 mg, daily plus simvastatin, 40 mg, daily vs placebo plus simvastatin, 40 mg, daily. In FOURIER, 1:1 randomization to evolocumab, 140 mg, every 2 weeks or 420 mg monthly vs matching placebo. The percentage LDL-C reduction at either 1 month (A to Z-TIMI 21, IMPROVE-IT) or 3 months (FOURIER) as a function of baseline LDL-C level. Data were modeled using a generalized linear regression model. A total of 3187 patients from A to Z-TIMI 21, 10 680 patients from IMPROVE-IT, and 25 847 patients from FOURIER were analyzed. There was a higher percentage reduction in LDL-C levels with evolocumab in patients with lower baseline LDL-C levels, ranging from 59.4% (95% CI, 59.1%-59.8%) in patients with a baseline LDL-C level of 130 mg/dL to 66.1% (95% CI, 65.6%-66.6%) in patients with a baseline LDL-C level of 70 mg/dL (P < .001). In contrast, across the same range of baseline LDL-C level, there was a more modest difference for simvastatin (44.6% [95% CI, 43.9%-45.2%] vs 47.8% [95% CI, 46.4%-49.2%]; P < .001) and minimal difference with ezetimibe (25.0% [95% CI, 23.3%-26.6%] vs 26.2% [95% CI, 24.2%-28.1%]; P = .007). The percentage LDL-C reduction with statins, ezetimibe, and PCSK9 inhibition is not attenuated in patients starting with lower baseline LDL-C levels and is 6.6% greater for PCSK9 inhibition. These data are encouraging for the use of intensive LDL-C-lowering therapy even for patients with lower LDL-C levels.

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Familial Resemblance in Low-Density Lipoprotein Cholesterol Response to Statins in the Danish Population.

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