cholesterol, LDL

Familial Hypercholesterolemia

Nathan Hinkle — Tue, 30 Jun 2026 21:32:37 +0000

Date Added:

June 30, 2026

Journal/Publication:

JAMA

Publisher:

The American Medical Association

Publication Date:

June 29, 2026

Pages:

E1-E3

URL:

Familial Hypercholesterolemia

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

doi: 10.1001/jama.2026.8822

Keywords

MeSH

cardiovascular diseases

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

Management of Blood Cholesterol

Jeffrey Wilson — Tue, 05 Feb 2019 20:01:21 +0000

Date Added:

February 5, 2019

Journal/Publication:

JAMA

Publisher:

American Medical Association

Publication Date:

February 4, 2019

URL:

Management of Blood Cholesterol

DOI (1):

doi:10.1001/jama.2019.0015

Keywords

MeSH

myocardial infarction

cholesterol

This is an update to the 2013 blood cholesterol guidelines developed by the AHA, ACC and others. It re-adds LDL targets and the addition of cholesterol-lowering agents other than statins when necessary.

Pharmacologically lowering low-density lipoprotein cholesterol (LDL-C) consistently reduces ASCVD events (myocardial infarction, stroke, and cardiovascular death), and the principle that lower LDL-C is better was reaffirmed by trials that added ezetimibe or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors to statin therapy. The 2013 guideline removed specific LDL-C treatment targets, but high-quality trials since offered the opportunity to reintroduce such goals based on risk gradations.

Author/s:

Alenghat, Francis J., Davis, Andrew M.

Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials

Tracy Ashby — Sun, 18 Feb 2018 06:00:00 +0000

Date Added:

February 18, 2019

Journal/Publication:

The Lancet

Publisher:

Elsevier Inc.

Publication Date:

February 2, 2019

Issue:

10170

Volume:

393

Pages:

407-415

URL:

Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1016/S0140-6736(18)31942-1

Keywords

statin

statin therapy

cholesterol, LDL

PMID (1):

30712900

MeSH

Hydroxymethylglutaryl-CoA Reductase Inhibitors

cholesterol

cholesterol, LDL

risk reduction behavior

Statins appear to work just as well in patients over the age of 75 as they do in younger patients.

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BACKGROUND:

Statin therapy has been shown to reduce major vascular events and vascular mortality in a wide range of individuals, but there is uncertainty about its efficacy and safetyamong older people. We undertook a meta-analysis of data from all large statin trials to compare the effects of statin therapy at different ages.

METHODS:

In this meta-analysis, randomised trials of statin therapy were eligible if they aimed to recruit at least 1000 participants with a scheduled treatment duration of at least 2 years. We analysed individual participant data from 22 trials (n=134 537) and detailed summary data from one trial (n=12 705) of statin therapy versus control, plus individual participant data from five trials of more intensive versus less intensive statin therapy (n=39 612). We subdivided participants into six age groups (55 years or younger, 56-60 years, 61-65 years, 66-70 years, 71-75 years, and older than 75 years). We estimated effects on major vascular events (ie, major coronary events, strokes, and coronary revascularisations), cause-specific mortality, and cancer incidence as the rate ratio (RR) per 1·0 mmol/L reduction in LDL cholesterol. We compared proportional risk reductions in different age subgroups by use of standard χ2 tests for heterogeneity when there were two groups, or trend when there were more than two groups.

FINDINGS:

14 483 (8%) of 186 854 participants in the 28 trials were older than 75 years at randomisation, and the median follow-up duration was 4·9 years. Overall, statin therapy or a more intensive statin regimen produced a 21% (RR 0·79, 95% CI 0·77-0·81) proportional reduction in major vascular events per 1·0 mmol/L reduction in LDL cholesterol. We observed a significant reduction in major vascular events in all age groups. Although proportional reductions in major vascular events diminished slightly with age, this trend was not statistically significant (ptrend=0·06). Overall, statin or more intensive therapy yielded a 24% (RR 0·76, 95% CI 0·73-0·79) proportional reduction in major coronary events per 1·0 mmol/L reduction in LDL cholesterol, and with increasing age, we observed a trend towards smaller proportional risk reductions in major coronary events (ptrend=0·009). We observed a 25% (RR 0·75, 95% CI 0·73-0·78) proportional reduction in the risk of coronary revascularisation procedures with statin therapy or a more intensive statin regimen per 1·0 mmol/L lower LDL cholesterol, which did not differ significantly across age groups (ptrend=0·6). Similarly, the proportional reductions in stroke of any type (RR 0·84, 95% CI 0·80-0·89) did not differ significantly across age groups (ptrend=0·7). After exclusion of four trials which enrolled only patients with heart failure or undergoing renal dialysis (among whom statin therapy has not been shown to be effective), the trend to smaller proportional risk reductions with increasing age persisted for major coronary events (ptrend=0·01), and remained non-significant for major vascular events (ptrend=0·3). The proportional reduction in major vascular events was similar, irrespective of age, among patients with pre-existing vascular disease (ptrend=0·2), but appeared smaller among older than among younger individuals not known to have vascular disease (ptrend=0·05). We found a 12% (RR 0·88, 95% CI 0·85-0·91) proportional reduction in vascular mortality per 1·0 mmol/L reduction in LDL cholesterol, with a trend towards smaller proportional reductions with older age (ptrend=0·004), but this trend did not persist after exclusion of the heart failure or dialysis trials (ptrend=0·2). Statin therapy had no effect at any age on non-vascular mortality, cancer death, or cancer incidence.

INTERPRETATION:

Statin therapy produces significant reductions in major vascular events irrespective of age, but there is less direct evidence of benefit among patients older than 75 years who do not already have evidence of occlusive vascular disease. This limitation is now being addressed by further trials.

FUNDING:

Australian National Health and Medical Research Council, National Institute for Health Research Oxford Biomedical Research Centre, UK Medical Research Council, and British Heart Foundation.

Author/s:

Cholesterol Treatment Trialists' Collaboration