Table 2.
Principal studies including data about prevalence of familial hypercholesterolemia and polygenic hypercholesterolemia.
| Study first author, year | N | Clinical characteristics | Time follow-up (years) | Number and genes with SNVs included for diagnosis of PH | Prevalence of PH (%), % of score | Prevalence of FH (%) | ASCVD risk FH | ASCVD risk associated to PH |
|---|---|---|---|---|---|---|---|---|
| Kathiresan et al. (2008) | 5,414 | Cardiovascular cohort Malmö Diet and Cancer Study | 10.6 | 9 (APOB, PCSK9 LDLR; CETP LIPC LPL, APOE, HMGCR, ABCA1) | 26.2 (>fourth quartile) | NA | NA | 1,63 hazard ratio |
| Willer et al. (2013) | 1,158 | PrH in proband plus family history of premature myocardial infarction | NA | 6 (CELSR2, APOB, ABCG5/8 LDLR and APOE) | 36 (>fourth quartile) | 351 (33,3) | NA | NA |
| Khera et al. (2016) | 26,025 | 5,540 coronary artery disease | NA | NA | NA | 1.9 | 22 | 6 (HC subjects non-FH) |
| Khera et al. (2018) | 2,081 | Early onset of myocardial infarction | NA | *6,6 × 106 | 17.3 (>95th decile) | 1.7 (LDLR truncation, frameshift, splicing) | 3.8 | 3.7 |
| Benn et al. (2012) | 69,016 | Danish community-based population | NA | NA | 6.9 (definitive, probable or possible FH) | 0.2 | 10.3 | NA |
| Benn et al. (2016) | 98,098 | Copenhagen general population Study | 36 | NA | 7.2 | 0.46 | 5.3 LDLR carriers 1.8 APOB carriers |
NA |
| Natarajan et al. (2018) | 16,324 | From 4 ancestries** | NA | 2 × 106-SNV LDL-C polygenic score | 23% of HC (>95th decile) | 2% of HC | NA | NA |
| Patel et al. (2019) | 1.18 × 106 | Geisinger Health System patients | NA | NA | 13.7 | 0.15 (definitive FH) | NA | 1.52 |
| Trinder et al. (2019) | 626 | British Columbia FH patients according to DLCN, <55 yr. and myocardial infarction | 7.2 | 28 | 21.4 (>80th percentile) | 43.9 (frameshift novel and no sense in LDLR and APOB mutations; LDLR variants <1% and pathogenic) | 1.97 | 1.39 |
| Trinder et al. (2020) | 48,718 | UK biobank | 7.2 | 223 | 4.9 (>95th percentile) | 0.57 | 1.93 | 1.29 |
Variants drawn were related to LDL-C and myocardial infarction trait.
Subjects with lipid profile available from Framingham Heart Study (FHS), Old Order Amish (OOA), Jackson Heart Study (JHS), Multi-Ethnic Study of Atherosclerosis (MESA), FINRISK Study (FIN), and Estonian Biobank (EST).
In case that PH score study was not available, data referred as PH express the prevalence of primary hypercholesterolemia (LDL-C >95th percentile) non-related to FH. Type of event evaluated were myocardial infarction, ischemic stroke, and death from coronary heart disease. “Definite,” “probable,” or “possible FH” was defined by the Dutch Lipid Clinic network score (>8, 6–8, 5–7, respectively). PH, polygenic hypercholesterolemia; FH, familial hypercholesterolemia; ASCVD, atherosclerotic cardiovascular disease; SNV, single nucleotide variation; NA, non-available; NS, non-significant.
APOB, apolipoprotein B; APOE, apolipoprotein E; CELSR2, cadherin; CETP, cholesteryl ester transfer protein; EGF LAG 7-pass G-type receptor 2; HMGCR, 3-hydroxy-3-methylglutaryl-coenzyme A reductase; LDLR, low-density lipoprotein receptor; LIPC, hepatic lipase; LPL, lipoprotein lipase; PCSK9, proprotein convertase subtilisin/kexin type 9.