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Atherosclerosis. 2019 May 24;287:8-15. doi: 10.1016/j.atherosclerosis.2019.05.017. [Epub ahead of print]

Risk of cardiovascular disease outcomes in primary care subjects with familial hypercholesterolaemia: A cohort study.

Author information

1
Primary Care Stratified Medicine Group, Division of Primary Care, University of Nottingham, UK. Electronic address: barbara.iyen@nottingham.ac.uk.
2
Primary Care Stratified Medicine Group, Division of Primary Care, University of Nottingham, UK.
3
Division of Epidemiology and Public Health, University of Nottingham, UK.
4
Faculty of Medicine, Primary Care and Population Sciences, University of Southampton, UK.
5
Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, UK.

Abstract

BACKGROUND AND AIMS:

Familial hypercholesterolaemia (FH) is a known major cause of premature heart disease. However, the risks of atherosclerotic disease in other vascular regions are less known. We determined the risk of major cardiovascular disease (CVD) outcomes associated with clinical FH.

METHODS:

In a retrospective cohort study (1 January, 1999 to 22 July, 2016), we randomly-matched 14,097 UK subjects with clinical FH diagnoses or characteristics (Simon-Broome definite or Dutch Lipid Clinic Score >8) to 42,506 subjects without FH by age, sex, general practice. We excluded those with CVD at baseline. Incident rates for coronary heart disease (CHD), stroke or transient ischaemic attack (TIA) and peripheral vascular disease (PVD) were estimated. Cox proportional hazards regression, stratified on matched-pairs, determined adjusted hazards ratios (HR) for incident CVD.

RESULTS:

During follow-up (median 13.8 years), incidence rates (95% CI) of CVD (per 1000 person-years) were 25.6 (24.8-26.3) in FH and 2.9 (2.8-3.1) in non-FH subjects. The risk of CHD, stroke/TIA and PVD was higher in FH compared to non-FH subjects: CHD (HR 10.63, 95% CI 9.82-11.49), stroke/TIA (HR 6.74, 95% CI 5.84-7.77), PVD (HR 7.17, 95% CI 6.08-8.46). The risk of CVD was greater in those with FH characteristics (HR 13.52, 95% CI 12.48-14.65) than those with clinical diagnoses (HR 1.66, 95% CI 1.42-1.93).

CONCLUSIONS:

In addition to the recognised increased risk of CHD, subjects with FH have greatly elevated risk of stroke/TIA and PVD. This emphasises need for early diagnosis and preventive interventions beyond CHD, to reduce CVD risk in these individuals.

KEYWORDS:

Cardiovascular disease; Coronary heart disease; Epidemiology; Familial hypercholesterolaemia; Peripheral vascular disease; Stroke

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