Characteristics of the 25 real-world observational studies included in the meta-analysis of sex differences in the treatment of familial hypercholesterolaemia with lipid-lowering therapies
| First author . | Year . | Country . | Study design . | Participants . | Diagnosis criteria . | Recruitment period . | Males n . | Females n . | On LLT . | LLT . | Baseline LDL-C . | Treated LDL-C . | LDL-C % change . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Agarwala20 | 2023 | USA | Retrospective cohort | HeFH | DLCN SB MEDPED AHA Genetic | NR | 280 | 502 | Statins M: 84.0% F: 78.0% | Statins Ezetimibe PCSK9i | NR | M: 3.00 ± 1.29 F: 3.23 ± 1.24 | NR |
| Amrock21 | 2017 | USA | Cross-sectional analysis of registry data | HeFH HoFH | SB DLCN MEDPED | 2014–16 | 1246 | 1921 | Statins M: 74.6% F: 66.7% | Statins Ezetimibe Bile acid seq Niacin PCSK9i | M: 6.27 ± 1.58 F: 6.31 ± 1.48 | M: 3.53 ± 1.69 F: 3.96 ± 1.86 | M: −43.7% F: −37.2% |
| Arnesen22 | 2020 | Norway | Retrospective cohort | HeFH | DLCN Genetic | 2006 | At last visit: 147 | At last visit: 127 | M: 96.6% F: 89.8% | Statins Ezetimibe Resins PCSK9i | NR | M: 2.8 (2.6–3.0) F: 3.3 (3.0–3.5) | NR |
| Beliard23 | 2014 | France | Cross-sectional | HeFH | SB DLCN Genetic | 1988–2011 | 826 | 843 | M: 89.4% F: 79.1% | Statins Ezetimibe Bile acid seq Fibrate | NR | NR | NR |
| Benn10 | 2012 | Denmark | Cross-sectional | HeFH | DLCN Genetic | 1977–2011 | 204 | 298 | M: 50.0% F: 47.0% | Statins Ezetimibe Bile acid seq other | NR | NR | NR |
| Gallo24 | 2017 | France | Prospective | HeFH | Genetic | 2015 | 56 | 56 | M: 94.6% F: 69.6% | Statins Ezetimibe | NR | NR | NR |
| Jackson26 | 2021 | USA | Retrospective cohort | FH | USA ICD code for FH | 2016–19 | 25 367 | 28 431 | Statins M: 65.8% F: 59.6% | Statins Ezetimibe PCSK9i, Fenofibrate Other | NR | NR | NR |
| Jiménez27 | 2023 | Spain | Retrospective cohort—registry | HeFH | DLCN Genetic | NR | 1583 | 1778 | Statins: 84.1% | Statins PCSK9i | NR | NR | NR |
| Korneva28 | 2019 | Russia | Retrospective cohort—registry | HeFH | DLCN | NR | 75 | 116 | Statins Overall: 65.0% M: 58.7% F: 69.0% | Statins | NR | NR | NR |
| Krogh29 | 2016 | Norway | Retrospective cohort—registry | FH | DLCN Genetic | 1989–2010 | 47 LLT data: 43 | 32 LLT data: 31 | Statins: M: 93.0% F: 87.1% | Statins Ezetimibe Bile acid seq Niacin Other | M: 9.8 ± 2.7 F: 9.4 ± 2.0 | M: 4.7 ± 2.8 F: 5.3 ± 2.0 | M: −52.0% F: −43.6% |
| Li30 | 2017 | China | Retrospective cohort | FH | DLCN Genetic | 2011–16 | 162 | 119 | CAD + M: 88.8% F: 78.6% CAD- M: 64.3% F: 57.1% | Statins | NR | NR | NR |
| Matta31 | 2021 | Argentina | Prospective study | FH | DLCN | 2015–20 | 30 | 85 | Statins M: 26.7% F: 38.8% | Statins | NR | NR | NR |
| Mattina32 | 2019 | France | Prospective study | FH | Genetic | 2015–16 | 70 | 84 | M: 92.9% F: 69.0% | Statins Ezetimibe | NR | NR | NR |
| Mundal11 | 2014 | Norway | Registry | HeFH HoFH | Genetic | 1992–2010 | 59 LLT data: 38 | 54 LLT data: 30 | 88.2% | Statins ± other LLT | NR | M: 4.4 ± 1.4 F: 5.0 ± 1.6 | NR |
| Neil33 | 2004 | UK | Cross-sectional study—registry | HeFH | SB | 1980–96 | 211 CAD+:104 CAD−:107 | 199 CAD+: 55 CAD−:144 | CAD + M: 99.0% F: 94.5% CAD− M: 92.5% F: 74.3% | Statins | NR | NR | NR |
| Pang34 | 2021 | Australia | Registry | FH | DLCN Genetic | 2015–19 | 771 | 757 | LLT M: 84.3% F: 77.3% | Statins Ezetimibe PCSK9i | M: 7.2 ± 2.6 F: 7.5 ± 2.4 | M: 3.6 ± 2.0 F: 4.1 ± 2.0 | M: −50.0% F: −45.3% |
| Pérez-Calahorra35 | 2017 | Spain | Cross-sectional analysis of registry data | HeFH | DLCN | 2013–16 | 851 | 881 | NR | NR | NR | NR | NR |
| Ryzhaya7 | 2021 | Canada | Retrospective longitudinal study using registry data | FH | DLCN | NR | 275 | 304 | Statins M: 89.6% F: 88.4% | Statins Ezetimibe PCSK9i | M: 6.93 ± 2.0 F: 6.83 ± 2.2 | M: 2.71 ± 1.7 F: 3.09 ± 1.2 | M: −60.9% F: −54.8% |
| Schreuder36 | 2023 | Netherlands Norway | Cross-sectional study | HeFH | DLCN Genetic | 2011–17 | 1465 | 1713 | Per type of LLT Table 1 | Statins Ezetimibe PCSK9i | M: 6.0 ± 1.7 F: 6.2 ± 1.6 | M: 2.8 ± .9 F: 3.1 ± 1.0 | M: −52.2% F: −50.5% |
| Vallejo-Vaz37 | 2018 | UK | Retrospective study | HeFH | Phenotypic | NR | 714 | 626 | M: 65.5% F: 65.5% | PCSK9i—Aliro 75/150mg | In mg/dL M: 150.8 ± 54.1 F: 159.6 ± 62.5 | NR | NR |
| Vallejo-Vaz6 | 2021 | Internationala | Retrospective cross-sectional—registry | HeFH | DLCN Genetic MEDPED SB Canadian JAS | NR | 19 031 | 21 999 | M: 61.1% F: 58.4% | Statins Ezetimibe Fibrates PCSK9i | NR | Median (IQR) M: 4.18 (3.16–5.51) F: 4.26 (3.24–5.75) | NR |
| Vlad38 | 2021 | Romania | Prospective cohort | FH | SB DLCN MEDPED | 2016–17 | 22 | 39 | Statins monotherapy at registration M: 39.8% F: 38.5% | Statins Ezetimibe Fibrates | NR | NR | NR |
| Waluś-Miarka39 | 2017 | Poland | Prospective cohort | FH | SB Genetic | 2011–13 | 63 | 91 | NR | NR | NR | NR | NR |
| Zamora8 | 2023 | Spain | Cross-sectional | FH-phenotype | Phenotypic | 2006–14 | 6747 CAD+: 1659 CAD−: 5088 | 7952 CAD+: 919 CAD−: 7033 | Per type of statin Table 2 | Statins Ezetimibe | Overall M: 7.35 ± .8 F: 7.35 ± .9 CAD + M: 7.44 ± .90 F: 7.44 ± .93 CAD− M: 7.31 ± .98 F: 7.34 ± .95 | Overall M: 4.23 ± 1.3 F: 4.50 ± 1.6 CAD + M: 3.41 ± 1.24 F: 3.77 ± 1.29 CAD− M: 4.62 ± 1.5 F: 4.65 ± 1.6 | Overall M: 42.4% F: 38.6% CAD + M: −54.2% F: −49.3% CAD− M: −36.8% F: −36.6% |
| Zhao40 | 2019 | Canada | Bi-directional cohort | FH | Canadian Genetic | NR | 80 | 102 | M: 10.0% F: 6.9% | NR | M: 6.04 ± 1.2 F: 6.35 ± 1.53 | M: 3.11 ± 1.41 F: 3.30 ± 1.48 | M: −48.5% F: −48.0% |
| First author . | Year . | Country . | Study design . | Participants . | Diagnosis criteria . | Recruitment period . | Males n . | Females n . | On LLT . | LLT . | Baseline LDL-C . | Treated LDL-C . | LDL-C % change . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Agarwala20 | 2023 | USA | Retrospective cohort | HeFH | DLCN SB MEDPED AHA Genetic | NR | 280 | 502 | Statins M: 84.0% F: 78.0% | Statins Ezetimibe PCSK9i | NR | M: 3.00 ± 1.29 F: 3.23 ± 1.24 | NR |
| Amrock21 | 2017 | USA | Cross-sectional analysis of registry data | HeFH HoFH | SB DLCN MEDPED | 2014–16 | 1246 | 1921 | Statins M: 74.6% F: 66.7% | Statins Ezetimibe Bile acid seq Niacin PCSK9i | M: 6.27 ± 1.58 F: 6.31 ± 1.48 | M: 3.53 ± 1.69 F: 3.96 ± 1.86 | M: −43.7% F: −37.2% |
| Arnesen22 | 2020 | Norway | Retrospective cohort | HeFH | DLCN Genetic | 2006 | At last visit: 147 | At last visit: 127 | M: 96.6% F: 89.8% | Statins Ezetimibe Resins PCSK9i | NR | M: 2.8 (2.6–3.0) F: 3.3 (3.0–3.5) | NR |
| Beliard23 | 2014 | France | Cross-sectional | HeFH | SB DLCN Genetic | 1988–2011 | 826 | 843 | M: 89.4% F: 79.1% | Statins Ezetimibe Bile acid seq Fibrate | NR | NR | NR |
| Benn10 | 2012 | Denmark | Cross-sectional | HeFH | DLCN Genetic | 1977–2011 | 204 | 298 | M: 50.0% F: 47.0% | Statins Ezetimibe Bile acid seq other | NR | NR | NR |
| Gallo24 | 2017 | France | Prospective | HeFH | Genetic | 2015 | 56 | 56 | M: 94.6% F: 69.6% | Statins Ezetimibe | NR | NR | NR |
| Jackson26 | 2021 | USA | Retrospective cohort | FH | USA ICD code for FH | 2016–19 | 25 367 | 28 431 | Statins M: 65.8% F: 59.6% | Statins Ezetimibe PCSK9i, Fenofibrate Other | NR | NR | NR |
| Jiménez27 | 2023 | Spain | Retrospective cohort—registry | HeFH | DLCN Genetic | NR | 1583 | 1778 | Statins: 84.1% | Statins PCSK9i | NR | NR | NR |
| Korneva28 | 2019 | Russia | Retrospective cohort—registry | HeFH | DLCN | NR | 75 | 116 | Statins Overall: 65.0% M: 58.7% F: 69.0% | Statins | NR | NR | NR |
| Krogh29 | 2016 | Norway | Retrospective cohort—registry | FH | DLCN Genetic | 1989–2010 | 47 LLT data: 43 | 32 LLT data: 31 | Statins: M: 93.0% F: 87.1% | Statins Ezetimibe Bile acid seq Niacin Other | M: 9.8 ± 2.7 F: 9.4 ± 2.0 | M: 4.7 ± 2.8 F: 5.3 ± 2.0 | M: −52.0% F: −43.6% |
| Li30 | 2017 | China | Retrospective cohort | FH | DLCN Genetic | 2011–16 | 162 | 119 | CAD + M: 88.8% F: 78.6% CAD- M: 64.3% F: 57.1% | Statins | NR | NR | NR |
| Matta31 | 2021 | Argentina | Prospective study | FH | DLCN | 2015–20 | 30 | 85 | Statins M: 26.7% F: 38.8% | Statins | NR | NR | NR |
| Mattina32 | 2019 | France | Prospective study | FH | Genetic | 2015–16 | 70 | 84 | M: 92.9% F: 69.0% | Statins Ezetimibe | NR | NR | NR |
| Mundal11 | 2014 | Norway | Registry | HeFH HoFH | Genetic | 1992–2010 | 59 LLT data: 38 | 54 LLT data: 30 | 88.2% | Statins ± other LLT | NR | M: 4.4 ± 1.4 F: 5.0 ± 1.6 | NR |
| Neil33 | 2004 | UK | Cross-sectional study—registry | HeFH | SB | 1980–96 | 211 CAD+:104 CAD−:107 | 199 CAD+: 55 CAD−:144 | CAD + M: 99.0% F: 94.5% CAD− M: 92.5% F: 74.3% | Statins | NR | NR | NR |
| Pang34 | 2021 | Australia | Registry | FH | DLCN Genetic | 2015–19 | 771 | 757 | LLT M: 84.3% F: 77.3% | Statins Ezetimibe PCSK9i | M: 7.2 ± 2.6 F: 7.5 ± 2.4 | M: 3.6 ± 2.0 F: 4.1 ± 2.0 | M: −50.0% F: −45.3% |
| Pérez-Calahorra35 | 2017 | Spain | Cross-sectional analysis of registry data | HeFH | DLCN | 2013–16 | 851 | 881 | NR | NR | NR | NR | NR |
| Ryzhaya7 | 2021 | Canada | Retrospective longitudinal study using registry data | FH | DLCN | NR | 275 | 304 | Statins M: 89.6% F: 88.4% | Statins Ezetimibe PCSK9i | M: 6.93 ± 2.0 F: 6.83 ± 2.2 | M: 2.71 ± 1.7 F: 3.09 ± 1.2 | M: −60.9% F: −54.8% |
| Schreuder36 | 2023 | Netherlands Norway | Cross-sectional study | HeFH | DLCN Genetic | 2011–17 | 1465 | 1713 | Per type of LLT Table 1 | Statins Ezetimibe PCSK9i | M: 6.0 ± 1.7 F: 6.2 ± 1.6 | M: 2.8 ± .9 F: 3.1 ± 1.0 | M: −52.2% F: −50.5% |
| Vallejo-Vaz37 | 2018 | UK | Retrospective study | HeFH | Phenotypic | NR | 714 | 626 | M: 65.5% F: 65.5% | PCSK9i—Aliro 75/150mg | In mg/dL M: 150.8 ± 54.1 F: 159.6 ± 62.5 | NR | NR |
| Vallejo-Vaz6 | 2021 | Internationala | Retrospective cross-sectional—registry | HeFH | DLCN Genetic MEDPED SB Canadian JAS | NR | 19 031 | 21 999 | M: 61.1% F: 58.4% | Statins Ezetimibe Fibrates PCSK9i | NR | Median (IQR) M: 4.18 (3.16–5.51) F: 4.26 (3.24–5.75) | NR |
| Vlad38 | 2021 | Romania | Prospective cohort | FH | SB DLCN MEDPED | 2016–17 | 22 | 39 | Statins monotherapy at registration M: 39.8% F: 38.5% | Statins Ezetimibe Fibrates | NR | NR | NR |
| Waluś-Miarka39 | 2017 | Poland | Prospective cohort | FH | SB Genetic | 2011–13 | 63 | 91 | NR | NR | NR | NR | NR |
| Zamora8 | 2023 | Spain | Cross-sectional | FH-phenotype | Phenotypic | 2006–14 | 6747 CAD+: 1659 CAD−: 5088 | 7952 CAD+: 919 CAD−: 7033 | Per type of statin Table 2 | Statins Ezetimibe | Overall M: 7.35 ± .8 F: 7.35 ± .9 CAD + M: 7.44 ± .90 F: 7.44 ± .93 CAD− M: 7.31 ± .98 F: 7.34 ± .95 | Overall M: 4.23 ± 1.3 F: 4.50 ± 1.6 CAD + M: 3.41 ± 1.24 F: 3.77 ± 1.29 CAD− M: 4.62 ± 1.5 F: 4.65 ± 1.6 | Overall M: 42.4% F: 38.6% CAD + M: −54.2% F: −49.3% CAD− M: −36.8% F: −36.6% |
| Zhao40 | 2019 | Canada | Bi-directional cohort | FH | Canadian Genetic | NR | 80 | 102 | M: 10.0% F: 6.9% | NR | M: 6.04 ± 1.2 F: 6.35 ± 1.53 | M: 3.11 ± 1.41 F: 3.30 ± 1.48 | M: −48.5% F: −48.0% |
AHA, American Heart Association; Bile acid seq., bile acid sequestrants; CAD, coronary artery disease; DLCN, Dutch Lipid Clinic Network; F, females; FH, familial hypercholesterolaemia; HeFH, heterozygous familial hypercholesterolaemia; HoFH, homozygous familial hypercholesterolaemia; ICD code, International Classification of Diseases; IQR, interquartile range; JAS, Japanese Atherosclerosis Society; LDL-C, low-density lipoprotein cholesterol; LLT, lipid-lowering therapy; M, males; MEDPED, Making Early Diagnosis to Prevent Early Deaths; mg, milligrams; NR, not reported; PCSK9i, proprotein convertase subtilisin/kexin type 9 inhibitor; SB, Simon Broome; UK, United Kingdom; USA, United States of America.
Values are mean ± standard and units in mmol/L unless otherwise stated.
Heath et al.25: Detailed data on treatment of FH per sex in the full group were not available, but data on LDL-C measurements in a subgroup of 47 males vs. 39 females with tendon xanthomas were included in the analyses shown in Figures 4 and 5.
a56 countries (of 66) participating in the European Atherosclerosis Society's Familial Hypercholesterolaemia Studies Collaboration.
Characteristics of the 25 real-world observational studies included in the meta-analysis of sex differences in the treatment of familial hypercholesterolaemia with lipid-lowering therapies
| First author . | Year . | Country . | Study design . | Participants . | Diagnosis criteria . | Recruitment period . | Males n . | Females n . | On LLT . | LLT . | Baseline LDL-C . | Treated LDL-C . | LDL-C % change . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Agarwala20 | 2023 | USA | Retrospective cohort | HeFH | DLCN SB MEDPED AHA Genetic | NR | 280 | 502 | Statins M: 84.0% F: 78.0% | Statins Ezetimibe PCSK9i | NR | M: 3.00 ± 1.29 F: 3.23 ± 1.24 | NR |
| Amrock21 | 2017 | USA | Cross-sectional analysis of registry data | HeFH HoFH | SB DLCN MEDPED | 2014–16 | 1246 | 1921 | Statins M: 74.6% F: 66.7% | Statins Ezetimibe Bile acid seq Niacin PCSK9i | M: 6.27 ± 1.58 F: 6.31 ± 1.48 | M: 3.53 ± 1.69 F: 3.96 ± 1.86 | M: −43.7% F: −37.2% |
| Arnesen22 | 2020 | Norway | Retrospective cohort | HeFH | DLCN Genetic | 2006 | At last visit: 147 | At last visit: 127 | M: 96.6% F: 89.8% | Statins Ezetimibe Resins PCSK9i | NR | M: 2.8 (2.6–3.0) F: 3.3 (3.0–3.5) | NR |
| Beliard23 | 2014 | France | Cross-sectional | HeFH | SB DLCN Genetic | 1988–2011 | 826 | 843 | M: 89.4% F: 79.1% | Statins Ezetimibe Bile acid seq Fibrate | NR | NR | NR |
| Benn10 | 2012 | Denmark | Cross-sectional | HeFH | DLCN Genetic | 1977–2011 | 204 | 298 | M: 50.0% F: 47.0% | Statins Ezetimibe Bile acid seq other | NR | NR | NR |
| Gallo24 | 2017 | France | Prospective | HeFH | Genetic | 2015 | 56 | 56 | M: 94.6% F: 69.6% | Statins Ezetimibe | NR | NR | NR |
| Jackson26 | 2021 | USA | Retrospective cohort | FH | USA ICD code for FH | 2016–19 | 25 367 | 28 431 | Statins M: 65.8% F: 59.6% | Statins Ezetimibe PCSK9i, Fenofibrate Other | NR | NR | NR |
| Jiménez27 | 2023 | Spain | Retrospective cohort—registry | HeFH | DLCN Genetic | NR | 1583 | 1778 | Statins: 84.1% | Statins PCSK9i | NR | NR | NR |
| Korneva28 | 2019 | Russia | Retrospective cohort—registry | HeFH | DLCN | NR | 75 | 116 | Statins Overall: 65.0% M: 58.7% F: 69.0% | Statins | NR | NR | NR |
| Krogh29 | 2016 | Norway | Retrospective cohort—registry | FH | DLCN Genetic | 1989–2010 | 47 LLT data: 43 | 32 LLT data: 31 | Statins: M: 93.0% F: 87.1% | Statins Ezetimibe Bile acid seq Niacin Other | M: 9.8 ± 2.7 F: 9.4 ± 2.0 | M: 4.7 ± 2.8 F: 5.3 ± 2.0 | M: −52.0% F: −43.6% |
| Li30 | 2017 | China | Retrospective cohort | FH | DLCN Genetic | 2011–16 | 162 | 119 | CAD + M: 88.8% F: 78.6% CAD- M: 64.3% F: 57.1% | Statins | NR | NR | NR |
| Matta31 | 2021 | Argentina | Prospective study | FH | DLCN | 2015–20 | 30 | 85 | Statins M: 26.7% F: 38.8% | Statins | NR | NR | NR |
| Mattina32 | 2019 | France | Prospective study | FH | Genetic | 2015–16 | 70 | 84 | M: 92.9% F: 69.0% | Statins Ezetimibe | NR | NR | NR |
| Mundal11 | 2014 | Norway | Registry | HeFH HoFH | Genetic | 1992–2010 | 59 LLT data: 38 | 54 LLT data: 30 | 88.2% | Statins ± other LLT | NR | M: 4.4 ± 1.4 F: 5.0 ± 1.6 | NR |
| Neil33 | 2004 | UK | Cross-sectional study—registry | HeFH | SB | 1980–96 | 211 CAD+:104 CAD−:107 | 199 CAD+: 55 CAD−:144 | CAD + M: 99.0% F: 94.5% CAD− M: 92.5% F: 74.3% | Statins | NR | NR | NR |
| Pang34 | 2021 | Australia | Registry | FH | DLCN Genetic | 2015–19 | 771 | 757 | LLT M: 84.3% F: 77.3% | Statins Ezetimibe PCSK9i | M: 7.2 ± 2.6 F: 7.5 ± 2.4 | M: 3.6 ± 2.0 F: 4.1 ± 2.0 | M: −50.0% F: −45.3% |
| Pérez-Calahorra35 | 2017 | Spain | Cross-sectional analysis of registry data | HeFH | DLCN | 2013–16 | 851 | 881 | NR | NR | NR | NR | NR |
| Ryzhaya7 | 2021 | Canada | Retrospective longitudinal study using registry data | FH | DLCN | NR | 275 | 304 | Statins M: 89.6% F: 88.4% | Statins Ezetimibe PCSK9i | M: 6.93 ± 2.0 F: 6.83 ± 2.2 | M: 2.71 ± 1.7 F: 3.09 ± 1.2 | M: −60.9% F: −54.8% |
| Schreuder36 | 2023 | Netherlands Norway | Cross-sectional study | HeFH | DLCN Genetic | 2011–17 | 1465 | 1713 | Per type of LLT Table 1 | Statins Ezetimibe PCSK9i | M: 6.0 ± 1.7 F: 6.2 ± 1.6 | M: 2.8 ± .9 F: 3.1 ± 1.0 | M: −52.2% F: −50.5% |
| Vallejo-Vaz37 | 2018 | UK | Retrospective study | HeFH | Phenotypic | NR | 714 | 626 | M: 65.5% F: 65.5% | PCSK9i—Aliro 75/150mg | In mg/dL M: 150.8 ± 54.1 F: 159.6 ± 62.5 | NR | NR |
| Vallejo-Vaz6 | 2021 | Internationala | Retrospective cross-sectional—registry | HeFH | DLCN Genetic MEDPED SB Canadian JAS | NR | 19 031 | 21 999 | M: 61.1% F: 58.4% | Statins Ezetimibe Fibrates PCSK9i | NR | Median (IQR) M: 4.18 (3.16–5.51) F: 4.26 (3.24–5.75) | NR |
| Vlad38 | 2021 | Romania | Prospective cohort | FH | SB DLCN MEDPED | 2016–17 | 22 | 39 | Statins monotherapy at registration M: 39.8% F: 38.5% | Statins Ezetimibe Fibrates | NR | NR | NR |
| Waluś-Miarka39 | 2017 | Poland | Prospective cohort | FH | SB Genetic | 2011–13 | 63 | 91 | NR | NR | NR | NR | NR |
| Zamora8 | 2023 | Spain | Cross-sectional | FH-phenotype | Phenotypic | 2006–14 | 6747 CAD+: 1659 CAD−: 5088 | 7952 CAD+: 919 CAD−: 7033 | Per type of statin Table 2 | Statins Ezetimibe | Overall M: 7.35 ± .8 F: 7.35 ± .9 CAD + M: 7.44 ± .90 F: 7.44 ± .93 CAD− M: 7.31 ± .98 F: 7.34 ± .95 | Overall M: 4.23 ± 1.3 F: 4.50 ± 1.6 CAD + M: 3.41 ± 1.24 F: 3.77 ± 1.29 CAD− M: 4.62 ± 1.5 F: 4.65 ± 1.6 | Overall M: 42.4% F: 38.6% CAD + M: −54.2% F: −49.3% CAD− M: −36.8% F: −36.6% |
| Zhao40 | 2019 | Canada | Bi-directional cohort | FH | Canadian Genetic | NR | 80 | 102 | M: 10.0% F: 6.9% | NR | M: 6.04 ± 1.2 F: 6.35 ± 1.53 | M: 3.11 ± 1.41 F: 3.30 ± 1.48 | M: −48.5% F: −48.0% |
| First author . | Year . | Country . | Study design . | Participants . | Diagnosis criteria . | Recruitment period . | Males n . | Females n . | On LLT . | LLT . | Baseline LDL-C . | Treated LDL-C . | LDL-C % change . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Agarwala20 | 2023 | USA | Retrospective cohort | HeFH | DLCN SB MEDPED AHA Genetic | NR | 280 | 502 | Statins M: 84.0% F: 78.0% | Statins Ezetimibe PCSK9i | NR | M: 3.00 ± 1.29 F: 3.23 ± 1.24 | NR |
| Amrock21 | 2017 | USA | Cross-sectional analysis of registry data | HeFH HoFH | SB DLCN MEDPED | 2014–16 | 1246 | 1921 | Statins M: 74.6% F: 66.7% | Statins Ezetimibe Bile acid seq Niacin PCSK9i | M: 6.27 ± 1.58 F: 6.31 ± 1.48 | M: 3.53 ± 1.69 F: 3.96 ± 1.86 | M: −43.7% F: −37.2% |
| Arnesen22 | 2020 | Norway | Retrospective cohort | HeFH | DLCN Genetic | 2006 | At last visit: 147 | At last visit: 127 | M: 96.6% F: 89.8% | Statins Ezetimibe Resins PCSK9i | NR | M: 2.8 (2.6–3.0) F: 3.3 (3.0–3.5) | NR |
| Beliard23 | 2014 | France | Cross-sectional | HeFH | SB DLCN Genetic | 1988–2011 | 826 | 843 | M: 89.4% F: 79.1% | Statins Ezetimibe Bile acid seq Fibrate | NR | NR | NR |
| Benn10 | 2012 | Denmark | Cross-sectional | HeFH | DLCN Genetic | 1977–2011 | 204 | 298 | M: 50.0% F: 47.0% | Statins Ezetimibe Bile acid seq other | NR | NR | NR |
| Gallo24 | 2017 | France | Prospective | HeFH | Genetic | 2015 | 56 | 56 | M: 94.6% F: 69.6% | Statins Ezetimibe | NR | NR | NR |
| Jackson26 | 2021 | USA | Retrospective cohort | FH | USA ICD code for FH | 2016–19 | 25 367 | 28 431 | Statins M: 65.8% F: 59.6% | Statins Ezetimibe PCSK9i, Fenofibrate Other | NR | NR | NR |
| Jiménez27 | 2023 | Spain | Retrospective cohort—registry | HeFH | DLCN Genetic | NR | 1583 | 1778 | Statins: 84.1% | Statins PCSK9i | NR | NR | NR |
| Korneva28 | 2019 | Russia | Retrospective cohort—registry | HeFH | DLCN | NR | 75 | 116 | Statins Overall: 65.0% M: 58.7% F: 69.0% | Statins | NR | NR | NR |
| Krogh29 | 2016 | Norway | Retrospective cohort—registry | FH | DLCN Genetic | 1989–2010 | 47 LLT data: 43 | 32 LLT data: 31 | Statins: M: 93.0% F: 87.1% | Statins Ezetimibe Bile acid seq Niacin Other | M: 9.8 ± 2.7 F: 9.4 ± 2.0 | M: 4.7 ± 2.8 F: 5.3 ± 2.0 | M: −52.0% F: −43.6% |
| Li30 | 2017 | China | Retrospective cohort | FH | DLCN Genetic | 2011–16 | 162 | 119 | CAD + M: 88.8% F: 78.6% CAD- M: 64.3% F: 57.1% | Statins | NR | NR | NR |
| Matta31 | 2021 | Argentina | Prospective study | FH | DLCN | 2015–20 | 30 | 85 | Statins M: 26.7% F: 38.8% | Statins | NR | NR | NR |
| Mattina32 | 2019 | France | Prospective study | FH | Genetic | 2015–16 | 70 | 84 | M: 92.9% F: 69.0% | Statins Ezetimibe | NR | NR | NR |
| Mundal11 | 2014 | Norway | Registry | HeFH HoFH | Genetic | 1992–2010 | 59 LLT data: 38 | 54 LLT data: 30 | 88.2% | Statins ± other LLT | NR | M: 4.4 ± 1.4 F: 5.0 ± 1.6 | NR |
| Neil33 | 2004 | UK | Cross-sectional study—registry | HeFH | SB | 1980–96 | 211 CAD+:104 CAD−:107 | 199 CAD+: 55 CAD−:144 | CAD + M: 99.0% F: 94.5% CAD− M: 92.5% F: 74.3% | Statins | NR | NR | NR |
| Pang34 | 2021 | Australia | Registry | FH | DLCN Genetic | 2015–19 | 771 | 757 | LLT M: 84.3% F: 77.3% | Statins Ezetimibe PCSK9i | M: 7.2 ± 2.6 F: 7.5 ± 2.4 | M: 3.6 ± 2.0 F: 4.1 ± 2.0 | M: −50.0% F: −45.3% |
| Pérez-Calahorra35 | 2017 | Spain | Cross-sectional analysis of registry data | HeFH | DLCN | 2013–16 | 851 | 881 | NR | NR | NR | NR | NR |
| Ryzhaya7 | 2021 | Canada | Retrospective longitudinal study using registry data | FH | DLCN | NR | 275 | 304 | Statins M: 89.6% F: 88.4% | Statins Ezetimibe PCSK9i | M: 6.93 ± 2.0 F: 6.83 ± 2.2 | M: 2.71 ± 1.7 F: 3.09 ± 1.2 | M: −60.9% F: −54.8% |
| Schreuder36 | 2023 | Netherlands Norway | Cross-sectional study | HeFH | DLCN Genetic | 2011–17 | 1465 | 1713 | Per type of LLT Table 1 | Statins Ezetimibe PCSK9i | M: 6.0 ± 1.7 F: 6.2 ± 1.6 | M: 2.8 ± .9 F: 3.1 ± 1.0 | M: −52.2% F: −50.5% |
| Vallejo-Vaz37 | 2018 | UK | Retrospective study | HeFH | Phenotypic | NR | 714 | 626 | M: 65.5% F: 65.5% | PCSK9i—Aliro 75/150mg | In mg/dL M: 150.8 ± 54.1 F: 159.6 ± 62.5 | NR | NR |
| Vallejo-Vaz6 | 2021 | Internationala | Retrospective cross-sectional—registry | HeFH | DLCN Genetic MEDPED SB Canadian JAS | NR | 19 031 | 21 999 | M: 61.1% F: 58.4% | Statins Ezetimibe Fibrates PCSK9i | NR | Median (IQR) M: 4.18 (3.16–5.51) F: 4.26 (3.24–5.75) | NR |
| Vlad38 | 2021 | Romania | Prospective cohort | FH | SB DLCN MEDPED | 2016–17 | 22 | 39 | Statins monotherapy at registration M: 39.8% F: 38.5% | Statins Ezetimibe Fibrates | NR | NR | NR |
| Waluś-Miarka39 | 2017 | Poland | Prospective cohort | FH | SB Genetic | 2011–13 | 63 | 91 | NR | NR | NR | NR | NR |
| Zamora8 | 2023 | Spain | Cross-sectional | FH-phenotype | Phenotypic | 2006–14 | 6747 CAD+: 1659 CAD−: 5088 | 7952 CAD+: 919 CAD−: 7033 | Per type of statin Table 2 | Statins Ezetimibe | Overall M: 7.35 ± .8 F: 7.35 ± .9 CAD + M: 7.44 ± .90 F: 7.44 ± .93 CAD− M: 7.31 ± .98 F: 7.34 ± .95 | Overall M: 4.23 ± 1.3 F: 4.50 ± 1.6 CAD + M: 3.41 ± 1.24 F: 3.77 ± 1.29 CAD− M: 4.62 ± 1.5 F: 4.65 ± 1.6 | Overall M: 42.4% F: 38.6% CAD + M: −54.2% F: −49.3% CAD− M: −36.8% F: −36.6% |
| Zhao40 | 2019 | Canada | Bi-directional cohort | FH | Canadian Genetic | NR | 80 | 102 | M: 10.0% F: 6.9% | NR | M: 6.04 ± 1.2 F: 6.35 ± 1.53 | M: 3.11 ± 1.41 F: 3.30 ± 1.48 | M: −48.5% F: −48.0% |
AHA, American Heart Association; Bile acid seq., bile acid sequestrants; CAD, coronary artery disease; DLCN, Dutch Lipid Clinic Network; F, females; FH, familial hypercholesterolaemia; HeFH, heterozygous familial hypercholesterolaemia; HoFH, homozygous familial hypercholesterolaemia; ICD code, International Classification of Diseases; IQR, interquartile range; JAS, Japanese Atherosclerosis Society; LDL-C, low-density lipoprotein cholesterol; LLT, lipid-lowering therapy; M, males; MEDPED, Making Early Diagnosis to Prevent Early Deaths; mg, milligrams; NR, not reported; PCSK9i, proprotein convertase subtilisin/kexin type 9 inhibitor; SB, Simon Broome; UK, United Kingdom; USA, United States of America.
Values are mean ± standard and units in mmol/L unless otherwise stated.
Heath et al.25: Detailed data on treatment of FH per sex in the full group were not available, but data on LDL-C measurements in a subgroup of 47 males vs. 39 females with tendon xanthomas were included in the analyses shown in Figures 4 and 5.
a56 countries (of 66) participating in the European Atherosclerosis Society's Familial Hypercholesterolaemia Studies Collaboration.
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