Cardiovascular Disease Risk Associated With Familial Hypercholesterolemia: A Systematic Review of the Literature
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Supporting information
Supporting information
Author(s)
Type
Journal Article
Abstract
Purpose
The goal of this study was to determine cardiovascular disease (CVD) risk associated with familial hypercholesterolemia (FH).
Methods
A systematic review of the published literature was conducted. All publications describing FH risk from PubMed (“cardiovascular disease risk + familial hypercholesterolaemia,” 2004–2015), Internet and Medline search of FH registries, and associated references were screened for FH-related CVD risk in titles, abstracts, and study methods. CVD risk expressed as rates, odds, or ratios of mortality and morbidity were extracted. Each article was reviewed for bias by 2 reviewers within 17 items in 7 categories; a modified Newcastle-Ottawa assessment scale was used for nonrandomized studies.
Findings
The complete literature search identified 712 potential publications: 549 from PubMed (Medline), 150 from registries, and 13 from references. Fourteen articles met the inclusion criteria: 8 from registries in the United Kingdom, the Netherlands, Norway, and Spain; 5 from single hospitals or families in Japan, Denmark, the Netherlands, and the United Kingdom; and a population survey in Denmark. Across studies, attrition bias was low in 22 (80%) of 28 items. Risk of selection bias was high in 35 (63%) of 56 items. Selection bias risk was due to low representativeness and lack of a non-FH comparator group within the same study; detection bias risk was due to variable definitions of CVD outcomes/measurement; and performance bias risk was due to long-term, intensive treatment, the most common limitations for registries. Studies from single hospitals and families lacked generalizability. In contrast, the Danish study revealed a low bias in each of the 4 selection bias criteria and 2 attrition risk criteria. Fatal and nonfatal CVD events were collected in the study. Comparing patients with FH versus non-FH patients, the odds ratios for coronary artery disease were 10.3 (95% CI, 7.8–13.8) and 13.2 (95% CI, 10.0–17.4) in subjects treated and not treated with lipid-lowering therapy, respectively. These ratios fall within the ranges of ratios reported in other studies but are generally higher than the ratios from registries and clinics, in which intensive specialized management is available.
Implications
There is a lack of available data describing CVD risk in patients with FH, and many of the existing studies have biases in their design that could affect their risk estimates. A Danish study had the highest quality based on a predefined quality check list, providing the most credible estimates of the increase in CVD risk in patients with FH. The CVD risk due to FH is high and represents unmet medical need for patients with FH. Further research is warranted to validate the magnitude of risk.
The goal of this study was to determine cardiovascular disease (CVD) risk associated with familial hypercholesterolemia (FH).
Methods
A systematic review of the published literature was conducted. All publications describing FH risk from PubMed (“cardiovascular disease risk + familial hypercholesterolaemia,” 2004–2015), Internet and Medline search of FH registries, and associated references were screened for FH-related CVD risk in titles, abstracts, and study methods. CVD risk expressed as rates, odds, or ratios of mortality and morbidity were extracted. Each article was reviewed for bias by 2 reviewers within 17 items in 7 categories; a modified Newcastle-Ottawa assessment scale was used for nonrandomized studies.
Findings
The complete literature search identified 712 potential publications: 549 from PubMed (Medline), 150 from registries, and 13 from references. Fourteen articles met the inclusion criteria: 8 from registries in the United Kingdom, the Netherlands, Norway, and Spain; 5 from single hospitals or families in Japan, Denmark, the Netherlands, and the United Kingdom; and a population survey in Denmark. Across studies, attrition bias was low in 22 (80%) of 28 items. Risk of selection bias was high in 35 (63%) of 56 items. Selection bias risk was due to low representativeness and lack of a non-FH comparator group within the same study; detection bias risk was due to variable definitions of CVD outcomes/measurement; and performance bias risk was due to long-term, intensive treatment, the most common limitations for registries. Studies from single hospitals and families lacked generalizability. In contrast, the Danish study revealed a low bias in each of the 4 selection bias criteria and 2 attrition risk criteria. Fatal and nonfatal CVD events were collected in the study. Comparing patients with FH versus non-FH patients, the odds ratios for coronary artery disease were 10.3 (95% CI, 7.8–13.8) and 13.2 (95% CI, 10.0–17.4) in subjects treated and not treated with lipid-lowering therapy, respectively. These ratios fall within the ranges of ratios reported in other studies but are generally higher than the ratios from registries and clinics, in which intensive specialized management is available.
Implications
There is a lack of available data describing CVD risk in patients with FH, and many of the existing studies have biases in their design that could affect their risk estimates. A Danish study had the highest quality based on a predefined quality check list, providing the most credible estimates of the increase in CVD risk in patients with FH. The CVD risk due to FH is high and represents unmet medical need for patients with FH. Further research is warranted to validate the magnitude of risk.
Date Issued
2016-05-31
Date Acceptance
2016-05-10
Citation
Clinical Therapeutics, 2016, 38 (7), pp.1696-1709
ISSN
1879-114X
Publisher
Elsevier
Start Page
1696
End Page
1709
Journal / Book Title
Clinical Therapeutics
Volume
38
Issue
7
Copyright Statement
© 2016 The Authors. Published by Elsevier HS Journals, Inc. This is an
open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
Subjects
bias
cardiovascular disease
familial hypercholesterolemia
lipid-modifying therapy
risk
Optoelectronics & Photonics
Pharmacology And Pharmaceutical Sciences
Publication Status
Accepted