Leo E Akioyamen1, Jacques Genest2, Anna Chu3, Happy Inibhunu4, Dennis T Ko5, Jack V Tu5. 1. Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; ICES, Toronto, Ontario, Canada. Electronic address: sele.akioyamen@mail.utoronto.ca. 2. Faculty of Medicine, McGill University, Montreal, Québec, Canada; McGill University Health Centre, Royal Victoria Hospital, Montreal, Québec, Canada. 3. Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; ICES, Toronto, Ontario, Canada. 4. Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. 5. Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; ICES, Toronto, Ontario, Canada; Schulich Heart Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
Abstract
BACKGROUND: Current data from individual studies present conflicting evidence about the relationship between risk factors and cardiovascular disease (CVD) in heterozygous familial hypercholesterolemia (FH). OBJECTIVES: We conducted a systematic review and meta-analysis to quantify the association between various CVD risk factors and CVD in FH. METHODS: We searched MEDLINE, EMBASE, Global Health, the Cochrane Library, and PubMed for English-language studies reporting adjusted-associations between cardiovascular, behavioral, or clinical risk factors and CVD with ≥ 100 participants. We calculated pooled odds ratios (ORs) with 95% confidence intervals (CIs) for selected risk factors with random-effects meta-analysis, from which we derived attributable risk estimates. RESULTS: We identified 27 studies representing 41,831 unique participants and 6629 CVD events. Age (OR: 1.07; 95% CI: 1.03, 1.10), male sex (OR: 1.95; 95% CI: 1.68, 2.23), hypertension (OR: 2.11; 95% CI: 1.64, 2.58), diabetes (OR: 1.95; 95% CI: 1.33, 2.57), body mass index (OR: 1.04; 95% CI: 1.03, 1.05), smoking (OR: 1.71; 95% CI: 1.30, 2.12), elevated lipoprotein(a) (OR: 1.90; 95% CI: 1.10, 2.71), low high-density lipoprotein cholesterol (OR: 1.39; 95% CI: 1.24, 1.53), and a family history of CVD (OR: 1.83, 95% CI: 1.58, 2.07) were found to be significant CVD risk factors in FH. Smoking, hypertension, and diabetes accounted for more than a quarter of CVD risk in FH individuals, whereas low-density lipoprotein cholesterol > 4.0 mmol/L accounted for 1 in 3 CVD cases. Meta-regression analyses found associations between low-density lipoprotein cholesterol (P = .045) and total cholesterol (P < .001) and CVD. Results were broadly consistent in sensitivity analyses. CONCLUSION: Several clinical risk factors are significantly and independently associated with CVD risk in patients with FH and should be targeted for modification. These data can also inform the selection of variables for prediction models to aid in risk stratifying patients.
BACKGROUND: Current data from individual studies present conflicting evidence about the relationship between risk factors and cardiovascular disease (CVD) in heterozygous familial hypercholesterolemia (FH). OBJECTIVES: We conducted a systematic review and meta-analysis to quantify the association between various CVD risk factors and CVD in FH. METHODS: We searched MEDLINE, EMBASE, Global Health, the Cochrane Library, and PubMed for English-language studies reporting adjusted-associations between cardiovascular, behavioral, or clinical risk factors and CVD with ≥ 100 participants. We calculated pooled odds ratios (ORs) with 95% confidence intervals (CIs) for selected risk factors with random-effects meta-analysis, from which we derived attributable risk estimates. RESULTS: We identified 27 studies representing 41,831 unique participants and 6629 CVD events. Age (OR: 1.07; 95% CI: 1.03, 1.10), male sex (OR: 1.95; 95% CI: 1.68, 2.23), hypertension (OR: 2.11; 95% CI: 1.64, 2.58), diabetes (OR: 1.95; 95% CI: 1.33, 2.57), body mass index (OR: 1.04; 95% CI: 1.03, 1.05), smoking (OR: 1.71; 95% CI: 1.30, 2.12), elevated lipoprotein(a) (OR: 1.90; 95% CI: 1.10, 2.71), low high-density lipoprotein cholesterol (OR: 1.39; 95% CI: 1.24, 1.53), and a family history of CVD (OR: 1.83, 95% CI: 1.58, 2.07) were found to be significant CVD risk factors in FH. Smoking, hypertension, and diabetes accounted for more than a quarter of CVD risk in FH individuals, whereas low-density lipoprotein cholesterol > 4.0 mmol/L accounted for 1 in 3 CVD cases. Meta-regression analyses found associations between low-density lipoprotein cholesterol (P = .045) and total cholesterol (P < .001) and CVD. Results were broadly consistent in sensitivity analyses. CONCLUSION: Several clinical risk factors are significantly and independently associated with CVD risk in patients with FH and should be targeted for modification. These data can also inform the selection of variables for prediction models to aid in risk stratifying patients.
Authors: F J Kinnear; E Wainwright; J E Bourne; F E Lithander; J Hamilton-Shield; A Searle Journal: BMC Health Serv Res Date: 2020-01-08 Impact factor: 2.655
Authors: Fiona Jane Kinnear; Fiona E Lithander; Aidan Searle; Graham Bayly; Christina Wei; David J Stensel; Alice E Thackray; Linda Hunt; Julian P H Shield Journal: BMJ Open Date: 2020-12-28 Impact factor: 2.692
Authors: Leo E Akioyamen; Anna Chu; Jacques Genest; Douglas S Lee; Husam Abdel-Qadir; Cynthia A Jackevicius; Patrick R Lawler; Maneesh Sud; Jacob A Udell; Harindra C Wijeysundera; Dennis T Ko Journal: CJC Open Date: 2022-05-20
Authors: Ari E Horton; Andrew C Martin; Shubha Srinivasan; Robert N Justo; Nicola K Poplawski; David Sullivan; Tom Brett; Clara K Chow; Stephen J Nicholls; Jing Pang; Gerald F Watts Journal: J Paediatr Child Health Date: 2022-07-15 Impact factor: 1.929
Authors: Fiona J Kinnear; Julian P Hamilton-Shield; David J Stensel; Graham Bayly; Aidan Searle; Alice E Thackray; Fiona E Lithander Journal: Pilot Feasibility Stud Date: 2020-04-02