Familial Hypercholesterolemia and Lipoprotein(a): A Gordian Knot in Cardiovascular Prevention
Abstract
:1. Introduction
2. Materials and Methods
3. Results
3.1. Familial Hypercholesterolemia
3.1.1. Definition and Prevalence of FH
3.1.2. Genetics of FH
3.1.3. Clinical Presentation of FH
3.1.4. Diagnosis of FH
3.1.5. Prognosis and Treatment of FH
3.2. Lipoprotein(a)
3.2.1. Molecular Properties of Lp(a)
3.2.2. Genetics of Lp(a)
3.2.3. Definition and Prevalence of High Lp(a)
3.2.4. Clinical Presentation of hyperLp(a)
3.2.5. Available and Upcoming Therapies for hyperLp(a)
4. Discussion
4.1. FH and hyperLp(a)
4.1.1. Prevalence of hyperLp(a) in FH Patients
Authors | Sample Size | Country | Diagnosis of FH | Results |
---|---|---|---|---|
Utermann et al. [62] | 381 | UK | Clinical | 102 FH patients vs. 279 healthy subjects: 41.3 vs. 14.1 mg/dL, p < 0.001. |
Langsted et al. [7] | 46,200 | Denmark | Clinical and Genetic | 42,934 Unlike vs. 1675 Possible vs. 184 Probable/Definite FH patients: 23 (22.8–23.3) vs. 32 (31–34) vs. 35 (29–41) mg/dL, p < 0.05 (using unadjusted LDL-C for Lp(a)-cholesterol). 43,699 Unlike vs. 2360 Possible vs. 141 Probable/Definite FH patients: 24 (23.5–24.1) vs. 22 (21–24) vs. 21 (16–26) mg/dL, p = 0.46 (after adjusting LDL-C for Lp(a)-cholesterol). Lp(a) concentrations were similar in those with and without FH mutations: 24 (23.4–14) mg/dL in 46,124 individuals without an FH mutation vs. 23 (9–36) mg/dL in 27 individuals with an LDLR mutation (p = 0.10 vs. no known mutation) vs. 21 (14–28) mg/dL in 49 individuals with an apolipoprotein B mutation (p = 0.52) and 22 (15–28) mg/dL in 76 individuals with any FH mutation (p = 0.64) |
Chan et al. [54] | 907 | N/A | Clinical and Genetic | 74 patients with FH (8.2%) were reclassified to unlike FH when LDL-C was corrected for Lp(a)-cholesterol. There were no significant differences detected in the proportion of pathogenic FH mutations (27.9% vs. 33.1%) between patients with increased and normal Lp(a) concentrations at a cutoff of 50 mg/dL (p = 0.05). |
Trinder et al. [8] | 37,877 | UK | Clinical and Genetic | British Columbia FH and Familial Combined Hyperlipidemia cohort; 391 FH patients vs. 245 non-FH patients: 28.7 (10.3–75.4) vs. 13 (10–48.9) mg/dL, p < 0.01. No significant differences were noted between carriers of a pathogenic variant in the LDLR or apolipoprotein B and noncarriers (1.43 log mg/dL vs. 1.42 log mg/dL, p = 0.97). UK Biobank cohort (n = 37,486); 221 patients with FH mutation vs. 37,265 without FH mutation: 10.7 (4.9–26.3) vs. 8.7 (4.0–25.8) mg/dL, p = 0.24. |
Kraft et al. [60] | 69 | South Africa | Clinical and Genetic | 26 HoFH patients vs. 43 HeFH relatives: 36.6 vs. 14.4 mg/dL, p = 0.004. |
Li et al. [51] | 8050 | China | Clinical and Genetic | 6250 Unlikely vs. 1519 Possible vs. 281 Probable/Definite FH patients: 51.8 vs. 57.1 vs. 60.5 mg/dL, p < 0.001. |
Leitersdorf et al. [63] | 216 | N/A | Clinical and Genetic | 99 FH patients vs. 117 controls: 33 vs. 22 mg/dL, p < 0.001. |
Mbewu et al. [64] | 277 | UK | Clinical and Genetic | 89 HeFH patients vs. 109 normocholesterolemic controls vs. 40 healthy controls: 22.7 vs. 10.0 vs. 9.1 mg/dL, p < 0.05. |
Alonso et al. [6] | 2917 | Spain | Genetic | 1960 HeFH patients vs. 957 non-FH relatives: 23.6 (9.6–59.2) vs. 21.0 (7–47.2) mg/dL, p < 0.001. 500 FH patients with null mutations vs. 246 FH patients with defect LDLR mutations: 24.4 vs. 21.5 mg/dL, p < 0.05. |
Tada et al. [56] | 4255 | Japan | Genetic | 198 FH patients with LDLR variants vs. 42 with PCSK9 variants vs. 4015 controls: 12.6 (9.4–33.9) vs. 21.1 (11.7–34.9) vs. 5 (2.7–8.1) mg/dL, p = 0.002 for the comparison between FH-LDLR or FH-PCSK9 with control group. |
Sun et al. [57] | 510 | China | Genetic | 259 HeFH patients vs. 255 matched non-FH controls: 28.9 (13.2–64.8) vs. 11.7 (5.3–26.9) mg/dL, p < 0.05. |
Guo et al. [59] | 48 | France | Genetic | 8 HoFH patients vs. 18 healthy subjects: 50 ± 32 vs. 20.6 ± 5.2 mg/dL, p < 0.001. |
Sjouke et al. [61] | 119 | Netherlands | Genetic | 22 unaffected relatives vs. 63 HeFH vs. 34 HoFH patients: 19.9 (11.1–41.5) vs. 24.4 (5.9–70.6) vs. 47.3 (14.9–111.7) mg/dL, p = 0.150. |
Lingenhel et al. [65] | 203 | South Africa | Genetic | 103 FH patients vs. 100 non-FH relatives: 35.4 ± 31 vs. 20.7 ± 18.1 mg/dL, p = 0.0014. |
Wiklund et al. [66] | 120 | Sweden | N/A | 47 HeFH patients vs. 47 controls matched for age and sex: 2.4 (2.5–124.5) vs. 9.7 (0.7–104) mg/dL), p < 0.001. |
4.1.2. Joint Effect of FH and hyperLp(a) on Cardiovascular Risk
4.1.3. Barriers to the Identification of FH
4.1.4. Cascade Lp(a) Testing in FH Patients
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Koutsogianni, A.D.; Adamidis, P.S.; Barkas, F.; Liberopoulos, E.; Su, T.-C.; Yamashita, S.; Liamis, G.; Rizzo, M. Familial Hypercholesterolemia and Lipoprotein(a): A Gordian Knot in Cardiovascular Prevention. Metabolites 2022, 12, 1065. https://doi.org/10.3390/metabo12111065
Koutsogianni AD, Adamidis PS, Barkas F, Liberopoulos E, Su T-C, Yamashita S, Liamis G, Rizzo M. Familial Hypercholesterolemia and Lipoprotein(a): A Gordian Knot in Cardiovascular Prevention. Metabolites. 2022; 12(11):1065. https://doi.org/10.3390/metabo12111065
Chicago/Turabian StyleKoutsogianni, Amalia Despoina, Petros Spyridonas Adamidis, Fotios Barkas, Evangelos Liberopoulos, Ta-Chen Su, Shizuya Yamashita, George Liamis, and Manfredi Rizzo. 2022. "Familial Hypercholesterolemia and Lipoprotein(a): A Gordian Knot in Cardiovascular Prevention" Metabolites 12, no. 11: 1065. https://doi.org/10.3390/metabo12111065