Familial Hypercholesterolemia

RPR Commentary: A review of familial hypercholesterolemia. The heterozygotic form is common enough to be important in primary care. The best screening test is the family history. James W. Mold, MD, MPH

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Familial hypercholesterolemia (FH) is a family of genetic disorders characterized by impaired hepatic clearance of low-density lipoprotein (LDL) particles, due to pathogenic variants that impair LDL receptor function.1,2 Lifelong elevation of LDL cholesterol (LDL-C) results in accelerated atherosclerosis and increased risk of atherosclerotic cardiovascular disease (ASCVD). Worldwide, heterozygous FH affects approximately 1 in 250 to 350 individuals, based on genetic epidemiology studies of pathogenic variants in FH-associated genes.1-3 Homozygous FH is rare, occurring in approximately 1 in 160 000 to 500 000 individuals.2 Among people with untreated heterozygous FH, approximately half of men develop fatal or nonfatal coronary events by age 50 years and approximately one-third of women by age 60 years.

Author/s:

James H. Stein, Matthew C. Tattersall

Evaluating the Association Between Low-Density Lipoprotein Cholesterol Reduction and Relative and Absolute Effects of Statin Treatment: A Systematic Review and Meta-analysis

Saige Blanchard — Thu, 10 Mar 2022 06:00:00 +0000

Date Added:

March 22, 2022

Journal/Publication:

JAMA Internal Medicine

Publisher:

American Medical Association

Publication Date:

March 14, 2022

URL:

Evaluating the Association Between Low-Density Lipoprotein Cholesterol Reduction and Relative and Absolute Effects of Statin Treatment: A Systematic Review and Meta-analysis

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jamainternmed.2022.0134

Keywords

PMID (1):

35285850

MeSH

male

female

Hydroxymethylglutaryl-CoA Reductase Inhibitors

cholesterol, LDL

Numbers Needed to Treat

The relatively small reductions in risk of CV events and death by statins appears to be unrelated to LDL cholesterol lowering. James W. Mold, MD, MPH

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Importance: The association between statin-induced reduction in low-density lipoprotein cholesterol (LDL-C) levels and the absolute risk reduction of individual, rather than composite, outcomes, such as all-cause mortality, myocardial infarction, or stroke, is unclear.

Objective: To assess the association between absolute reductions in LDL-C levels with treatment with statin therapy and all-cause mortality, myocardial infarction, and stroke to facilitate shared decision-making between clinicians and patients and inform clinical guidelines and policy.

Data sources: PubMed and Embase were searched to identify eligible trials from January 1987 to June 2021.

Study selection: Large randomized clinical trials that examined the effectiveness of statins in reducing total mortality and cardiovascular outcomes with a planned duration of 2 or more years and that reported absolute changes in LDL-C levels. Interventions were treatment with statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) vs placebo or usual care. Participants were men and women older than 18 years.

Data extraction and synthesis: Three independent reviewers extracted data and/or assessed the methodological quality and certainty of the evidence using the risk of bias 2 tool and Grading of Recommendations, Assessment, Development and Evaluation. Any differences in opinion were resolved by consensus. Meta-analyses and a meta-regression were undertaken.

Main outcomes and measures: Primary outcome: all-cause mortality. Secondary outcomes: myocardial infarction, stroke.

Findings: Twenty-one trials were included in the analysis. Meta-analyses showed reductions in the absolute risk of 0.8% (95% CI, 0.4%-1.2%) for all-cause mortality, 1.3% (95% CI, 0.9%-1.7%) for myocardial infarction, and 0.4% (95% CI, 0.2%-0.6%) for stroke in those randomized to treatment with statins, with associated relative risk reductions of 9% (95% CI, 5%-14%), 29% (95% CI, 22%-34%), and 14% (95% CI, 5%-22%) respectively. A meta-regression exploring the potential mediating association of the magnitude of statin-induced LDL-C reduction with outcomes was inconclusive.

Conclusions and relevance: The results of this meta-analysis suggest that the absolute risk reductions of treatment with statins in terms of all-cause mortality, myocardial infarction, and stroke are modest compared with the relative risk reductions, and the presence of significant heterogeneity reduces the certainty of the evidence. A conclusive association between absolute reductions in LDL-C levels and individual clinical outcomes was not established, and these findings underscore the importance of discussing absolute risk reductions when making informed clinical decisions with individual patients.

Author/s:

Byrne, P., Demasi, M., Jones, M., Smith, S. M., O'Brien, K. K., DuBroff, R.