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

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

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.

Cardiovascular disease, Coronary heart disease, Epidemiology, Familial hypercholesterolaemia, Peripheral vascular disease, Stroke
0021-9150
8-15
Iyen, Barbara
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Qureshi, Nadeem
48c1e15a-f152-4532-b657-ed2877dc0b6b
Kai, Joe
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Akyea, Ralph K.
e65a6890-0e13-412f-bdc3-d0618d755274
Leonardi-Bee, Jo
746173bf-9dc1-456d-81b0-50e11a299dd8
Roderick, Paul
dbb3cd11-4c51-4844-982b-0eb30ad5085a
Humphries, Steve E.
00daa3dd-2447-4e61-b130-f8bc97ca1b78
Weng, Stephen
9d90d74c-43a3-4050-93ab-9843bf1d95da
Iyen, Barbara
eece1033-b6f3-4936-88de-0d5330e17f0d
Qureshi, Nadeem
48c1e15a-f152-4532-b657-ed2877dc0b6b
Kai, Joe
4149b8ab-84df-46e1-8735-4599809387e9
Akyea, Ralph K.
e65a6890-0e13-412f-bdc3-d0618d755274
Leonardi-Bee, Jo
746173bf-9dc1-456d-81b0-50e11a299dd8
Roderick, Paul
dbb3cd11-4c51-4844-982b-0eb30ad5085a
Humphries, Steve E.
00daa3dd-2447-4e61-b130-f8bc97ca1b78
Weng, Stephen
9d90d74c-43a3-4050-93ab-9843bf1d95da

Iyen, Barbara, Qureshi, Nadeem, Kai, Joe, Akyea, Ralph K., Leonardi-Bee, Jo, Roderick, Paul, Humphries, Steve E. and Weng, Stephen (2019) Risk of cardiovascular disease outcomes in primary care subjects with familial hypercholesterolaemia: a cohort study. Atherosclerosis, 287, 8-15. (doi:10.1016/j.atherosclerosis.2019.05.017).

Record type: Article

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.

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Accepted/In Press date: 23 May 2019
e-pub ahead of print date: 24 May 2019
Published date: 1 August 2019
Keywords: Cardiovascular disease, Coronary heart disease, Epidemiology, Familial hypercholesterolaemia, Peripheral vascular disease, Stroke

Identifiers

Local EPrints ID: 431946
URI: http://eprints.soton.ac.uk/id/eprint/431946
ISSN: 0021-9150
PURE UUID: 6bc60c7d-a9eb-4874-b7b7-eda27e2f8d8b
ORCID for Paul Roderick: ORCID iD orcid.org/0000-0001-9475-6850

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Date deposited: 24 Jun 2019 16:30
Last modified: 18 Mar 2024 02:40

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Contributors

Author: Barbara Iyen
Author: Nadeem Qureshi
Author: Joe Kai
Author: Ralph K. Akyea
Author: Jo Leonardi-Bee
Author: Paul Roderick ORCID iD
Author: Steve E. Humphries
Author: Stephen Weng

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