Defining severe familial hypercholesterolaemia and the implications for clinical management: a consensus statement from the International Atherosclerosis Society Severe Familial Hypercholesterolemia Panel

The Lancet Diabetes and Endocrinology

Volumn 4, Issue 10, 2016, Pages 850-861

  Santos, Raul D ^a   Gidding, Samuel S ^b   Hegele, Robert A ^c   Cuchel, Marina A ^d   Barter, Philip J ^e   Watts, Gerald F ^f   Baum, Seth J ^g   Catapano, Alberico L ^h,i   Chapman, M John ^j   Defesche, Joep C ^k   Folco, Emanuela ^m   Freiberger, Tomas ⁿ   Genest, Jacques ^o   Hovingh, G Kees ^k   Harada Shiba, Mariko ^p   Humphries, Steve E ^q   Jackson, Ann S ^l   Mata, Pedro ^r   Moriarty, Patrick M ^s   Raal, Frederick J ^t   Al Rasadi, Khalid ^u   Ray, Kausik K ^v   Reiner, Zelijko ^w   Sijbrands, Eric J G ^x   Yamashita, Shizuya ^y   more..

^a UNIVERSITY OF SÃO PAULO   (Brazil)

^b NEMOURS ALFRED I DUPONT HOSPITAL FOR CHILDREN   (United States)

^c ROBARTS RESEARCH INSTITUTE   (Canada)

^d UNIVERSITY OF PENNSYLVANIA   (United States)

^e UNIVERSITY OF NEW SOUTH WALES   (Australia)

^f UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^g BOCA RATON REGIONAL HOSPITAL   (United States)

^h UNIVERSITY OF MILAN   (Italy)

ⁱ IRCCS MULTIMEDICA   (Italy)

^j PITIÉ SALPÊTRIÈRE HOSPITAL   (France)

^k UNIVERSITY OF AMSTERDAM   (Netherlands)

^l International Atherosclerosis Society   (United States)

^m International Atherosclerosis Society   (Italy)

ⁿ MASARYK UNIVERSITY   (Czech Republic)

^o ROYAL VICTORIA HOSPITAL   (Canada)

^p NATIONAL CEREBRAL AND CARDIOVASCULAR CENTER   (Japan)

^q UNIVERSITY COLLEGE LONDON   (United Kingdom)

^r Medicina Interna   (Spain)

^s UNIVERSITY OF KANSAS MEDICAL CENTER   (United States)

^t UNIVERSITY OF THE WITWATERSRAND   (South Africa)

^u SULTAN QABOOS UNIVERSITY HOSPITAL   (Oman)

^v IMPERIAL COLLEGE LONDON   (United Kingdom)

^w Institute for Cardiovascular Prevention and Rehabilitation   (Croatia)

^x ERASMUS MEDICAL CENTER   (Netherlands)

^y OSAKA UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ALIROCUMAB; EVOLOCUMAB; LOMITAPIDE; MIPOMERSEN; PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9 INHIBITOR; SERINE PROTEINASE INHIBITOR; UNCLASSIFIED DRUG; LOW DENSITY LIPOPROTEIN CHOLESTEROL;

APHERESIS; BLOATING; CORONARY ARTERY ATHEROSCLEROSIS; DISEASE SEVERITY; DRUG EFFICACY; DRUG SAFETY; EPIGENETICS; FAMILIAL HYPERCHOLESTEROLEMIA; FLU LIKE SYNDROME; GENETIC ASSOCIATION; GENETIC HETEROGENEITY; GENETIC VARIABILITY; GENOTYPE ENVIRONMENT INTERACTION; GLOMERULUS FILTRATION RATE; HEADACHE; HETEROZYGOSITY; HOMOZYGOSITY; HUMAN; INJECTION SITE REACTION; MEDICAL SOCIETY; NAUSEA; NEXT GENERATION SEQUENCING; PERSONALIZED MEDICINE; PRIORITY JOURNAL; PROSPECTIVE STUDY; REIMBURSEMENT; REVIEW; RHINOPHARYNGITIS; RISK ASSESSMENT; RISK FACTOR; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; VOMITING; BLOOD; CARDIOVASCULAR DISEASE; COMPLICATION; FEMALE; MALE; PRACTICE GUIDELINE;

CARDIOVASCULAR DISEASES; CHOLESTEROL, LDL; FEMALE; HUMANS; HYPERLIPOPROTEINEMIA TYPE II; MALE; PRACTICE GUIDELINES AS TOPIC; RISK FACTORS; SOCIETIES, MEDICAL;

EID: 84969962145     PISSN: 22138587     EISSN: 22138595     Source Type: Journal    
DOI: 10.1016/S2213-8587(16)30041-9     Document Type: Review

References (95)

1. 1 Gidding, SS, Champagne, MA, de Ferranti, SD, et al. The agenda for familial hypercholesterolemia: a scientific statement from the American Heart Association. Circulation 132 (2015), 2167–2192.
2. 2 Benn, M, Watts, GF, Tybjaerg-Hansen, A, Nordestgaard, BG, Familial hypercholesterolemia in the Danish general population: prevalence, coronary artery disease, and cholesterol-lowering medication. J Clin Endocrinol Metab 97 (2012), 3956–3964.
3. 3 Watts, GF, Gidding, S, Wierzbicki, AS, et al. Integrated guidance on the care of familial hypercholesterolemia from the International FH Foundation. J Clin Lipidol 8 (2014), 148–172.
4. 4 Cuchel, M, Bruckert, E, Ginsberg, HN, et al. Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management—a position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. Eur Heart J 35 (2014), 2146–2157.
5. 5 Nordestgaard, BG, Chapman, MJ, Humphries, SE, et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J, 34, 2013, 3478 390a.
6. 6 Lahtinen, AM, Havulinna, AS, Jula, A, Salomaa, V, Kontula, K, Prevalence and clinical correlates of familial hypercholesterolemia founder mutations in the general population. Atherosclerosis 238 (2015), 64–69.
7. 7 Raal, FJ, Santos, RD, Homozygous familial hypercholesterolemia: current perspectives on diagnosis and treatment. Atherosclerosis 223 (2012), 262–268.
8. 8 Sjouke, B, Kusters, DM, Kindt, I, et al. Homozygous autosomal dominant hypercholesterolaemia in the Netherlands: prevalence, genotype-phenotype relationship, and clinical outcome. Eur Heart J 36 (2015), 560–565.
9. 9 Austin, MA, Hutter, CM, Zimmern, RL, Humphries, SE, Familial hypercholesterolemia and coronary heart disease: a HuGE association review. Am J Epidemiol 160 (2004), 421–429.
10. 10 Baum, SJ, Sijbrands, EJ, Mata, P, Watts, GF, The doctor's dilemma: challenges in the diagnosis and care of homozygous familial hypercholesterolemia. J Clin Lipidol 8 (2014), 542–549.
11. 11 Bertolini, S, Pisciotta, L, Rabacchi, C, et al. Spectrum of mutations and phenotypic expression in patients with autosomal dominant hypercholesterolemia identified in Italy. Atherosclerosis 227 (2013), 342–348.
12. 12 Raal, FJ, Santos, RD, Blom, DJ, et al. Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial. Lancet 375 (2010), 998–1006.
13. 13 Cuchel, M, Meagher, EA, du Toit Theron, H, et al. Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm, open-label, phase 3 study. Lancet 381 (2013), 40–46.
14. 14 Raal, FJ, Stein, EA, Dufour, R, et al., for the RUTHERFORD-2 Investigators. PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial. Lancet 385 (2015), 331–340.
15. 15 Talmud, PJ, Shah, S, Whittall, R, et al. Use of low-density lipoprotein cholesterol gene score to distinguish patients with polygenic and monogenic familial hypercholesterolaemia: a case-control study. Lancet 381 (2013), 1293–1301.
16. 16 Futema, M, Shah, S, Cooper, JA, et al. Refinement of variant selection for the LDL cholesterol genetic risk score in the diagnosis of the polygenic form of clinical familial hypercholesterolemia and replication in samples from 6 countries. Clin Chem 61 (2015), 231–238.
17. 17 Souverein, OW, Defesche, JC, Zwinderman, AH, Kastelein, JJ, Tanck, MW, Influence of LDL-receptor mutation type on age at first cardiovascular event in patients with familial hypercholesterolaemia. Eur Heart J 28 (2007), 299–304.
18. 18 Neil, A, Cooper, J, Betteridge, J, et al. Reductions in all-cause, cancer, and coronary mortality in statin-treated patients with heterozygous familial hypercholesterolaemia: a prospective registry study. Eur Heart J 29 (2008), 2625–2633.
19. 19 Yeboah, J, McClelland, RL, Polonsky, TS, et al. Comparison of novel risk markers for improvement in cardiovascular risk assessment in intermediate-risk individuals. JAMA 308 (2012), 788–795.
20. 20 Cho, I, Chang, HJ, Hartaigh, BO, et al. Incremental prognostic utility of coronary CT angiography for asymptomatic patients based upon extent and severity of coronary artery calcium: results from the COronary CT Angiography EvaluatioN For Clinical Outcomes InteRnational Multicenter (CONFIRM) study. Eur Heart J 36 (2015), 501–508.
21. 21 Tada, H, Kawashiri, MA, Okada, H, et al. Assessment of coronary atherosclerosis in patients with familial hypercholesterolemia by coronary computed tomography angiography. Am J Cardiol 115 (2015), 724–729.
22. 22 Besseling, J, Kindt, I, Hof, M, Kastelein, JJ, Hutten, BA, Hovingh, GK, Severe heterozygous familial hypercholesterolemia and risk for cardiovascular disease: a study of a cohort of 14 000 mutation carriers. Atherosclerosis 233 (2014), 219–223.
23. 23 Santos, RD, Raal, FJ, Catapano, AL, Witztum, JL, Steinhagen-Thiessen, E, Tsimikas, S, Mipomersen, an antisense oligonucleotide to apolipoprotein B-100, reduces lipoprotein(a) in various populations with hypercholesterolemia: results of 4 phase III trials. Arterioscler Thromb Vasc Biol 35 (2015), 689–699.
24. 24 Kastelein, JJ, Ginsberg, HN, Langslet, G, et al. ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia. Eur Heart J 36 (2015), 2996–3003.
25. 25 Weintraub, WS, Gidding, SS, PCSK9 inhibitors: a technology worth paying for?. PharmacoEconomics 34 (2016), 217–220.
26. 26 Milani, RV, Lavie, CJ, Lipid control in the modern era: an orphan's tale of rags to riches. J Am Coll Cardiol 62 (2013), 2185–2187.
27. 27 Di Angelantonio, E, Gao, P, Pennells, L, et al. Lipid-related markers and cardiovascular disease prediction. JAMA 307 (2012), 2499–2506.
28. 28 Teslovich, TM, Musunuru, K, Smith, AV, et al. Biological, clinical and population relevance of 95 loci for blood lipids. Nature 466 (2010), 707–713.
29. 29 Cohen, JC, Boerwinkle, E, Mosley, TH Jr, Hobbs, HH, Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med 354 (2006), 1264–1272.
30. 30 Ference, BA, Yoo, W, Alesh, I, et al. Effect of long-term exposure to lower low-density lipoprotein cholesterol beginning early in life on the risk of coronary heart disease: a Mendelian randomization analysis. J Am Coll Cardiol 60 (2012), 2631–2639.
31. 31 Cholesterol Treatment Trialists' (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 376 (2010), 1670–1681.
32. 32 Cannon, CP, Blazing, MA, Braunwald, E, Ezetimibe plus a statin after acute coronary syndromes. N Engl J Med 373 (2015), 1476–1477.
33. 33 Lakoski, SG, Lagace, TA, Cohen, JC, Horton, JD, Hobbs, HH, Genetic and metabolic determinants of plasma PCSK9 levels. J Clin Endocrinol Metab 94 (2009), 2537–2543.
34. 34 Horton, JD, Cohen, JC, Hobbs, HH, PCSK9: a convertase that coordinates LDL catabolism. J Lipid Res 50:suppl (2009), S172–S177.
35. 35 Kolansky, DM, Cuchel, M, Clark, BJ, et al. Longitudinal evaluation and assessment of cardiovascular disease in patients with homozygous familial hypercholesterolemia. Am J Cardiol 102 (2008), 1438–1443.
36. 36 Thompson, GR, Managing homozygous familial hypercholesterolaemia from cradle to grave. Atheroscler Suppl 18 (2015), 16–20.
37. 37 Scientific Steering Committee on behalf of the Simon Broome Register Group. Risk of fatal coronary heart disease in familial hypercholesterolaemia. BMJ 303 (1991), 893–896.
38. 38 Do, R, Stitziel, NO, Won, HH, et al. Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction. Nature 518 (2015), 102–106.
39. 39 Nanchen, D, Gencer, B, Auer, R, et al. Prevalence and management of familial hypercholesterolaemia in patients with acute coronary syndromes. Eur Heart J 36 (2015), 2438–2445.
40. 40 Raal, FJ, Pilcher, GJ, Panz, VR, et al. Reduction in mortality in subjects with homozygous familial hypercholesterolemia associated with advances in lipid-lowering therapy. Circulation 124 (2011), 2202–2207.
41. 41 Thompson, GR, Seed, M, Naoumova, RP, et al. Improved cardiovascular outcomes following temporal advances in lipid-lowering therapy in a genetically-characterised cohort of familial hypercholesterolaemia homozygotes. Atherosclerosis 243 (2015), 328–333.
42. 42 Stefanutti, C, Thompson, GR, Lipoprotein apheresis in the management of familial hypercholesterolaemia: historical perspective and recent advances. Curr Atheroscler Rep, 17, 2015, 465.
43. 43 Pijlman, AH, Huijgen, R, Verhagen, SN, et al. Evaluation of cholesterol lowering treatment of patients with familial hypercholesterolemia: a large cross-sectional study in the Netherlands. Atherosclerosis 209 (2010), 189–194.
44. 44 Perez de Isla, L, Alonso, R, Watts, GF, et al., for the SAFEHEART Investigators. Attainment of LDL-cholesterol treatment goals in patients with familial hypercholesterolemia: 5-year SAFEHEART Registry follow-up. J Am Coll Cardiol 67 (2016), 1278–1285.
45. 45 Wiegman, A, Gidding, SS, Watts, GF, et al. Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment. Eur Heart J 36 (2015), 2425–2437.
46. 46 Brautbar, A, Leary, E, Rasmussen, K, Wilson, DP, Steiner, RD, Virani, S, Genetics of familial hypercholesterolemia. Curr Atheroscler Rep, 17, 2015, 491.
47. 47 Moorjani, S, Roy, M, Torres, A, et al. Mutations of low-density-lipoprotein-receptor gene, variation in plasma cholesterol, and expression of coronary heart disease in homozygous familial hypercholesterolaemia. Lancet 341 (1993), 1303–1306.
48. 48 van der Graaf, A, Avis, HJ, Kusters, DM, et al. Molecular basis of autosomal dominant hypercholesterolemia: assessment in a large cohort of hypercholesterolemic children. Circulation 123 (2011), 1167–1173.
49. 49 Taylor, A, Bayly, G, Patel, K, et al. A double heterozygote for familial hypercholesterolaemia and familial defective apolipoprotein B-100. Ann Clin Biochem 47 (2010), 487–490.
50. 50 Hopkins, PN, Wu, LL, Schumacher, MC, et al. Type III dyslipoproteinemia in patients heterozygous for familial hypercholesterolemia and apolipoprotein E2: evidence for a gene-gene interaction. Arterioscler Thromb Vasc Biol 11 (1991), 1137–1146.
51. 51 Emi, M, Hegele, RM, Hopkins, PN, et al. Effects of three genetic loci in a pedigree with multiple lipoprotein phenotypes. Arterioscler Thromb Vasc Biol 11 (1991), 1349–1355.
52. 52 Besseling, J, Huijgen, R, Martin, SS, Hutten, BA, Kastelein, JJ, Hovingh, GK, Clinical phenotype in relation to the distance-to-index-patient in familial hypercholesterolemia. Atherosclerosis 246 (2015), 1–6.
53. 53 Sijbrands, EJ, Westendorp, RG, Defesche, JC, de Meier, PH, Smelt, AH, Kastelein, JJ, Mortality over two centuries in large pedigree with familial hypercholesterolaemia: family tree mortality study. BMJ 322 (2001), 1019–1023.
54. 54 Williams, RR, Hasstedt, SJ, Wilson, DE, et al. Evidence that men with familial hypercholesterolemia can avoid early coronary death: an analysis of 77 gene carriers in four Utah pedigrees. JAMA 255 (1986), 219–224.
55. 55 Bima, AI, Hooper, AJ, van Bockxmeer, FM, Burnett, JR, Hypobetalipoproteinaemia secondary to chronic hepatitis C virus infection in a patient with familial hypercholesterolaemia. Ann Clin Biochem 46 (2009), 420–422.
56. 56 Guay, SP, Brisson, D, Lamarche, B, Gaudet, D, Bouchard, L, Epipolymorphisms within lipoprotein genes contribute independently to plasma lipid levels in familial hypercholesterolemia. Epigenetics 9 (2014), 718–729.
57. 57 Couture, P, Brun, LD, Szots, F, et al. Association of specific LDL receptor gene mutations with differential plasma lipoprotein response to simvastatin in young French Canadians with heterozygous familial hypercholesterolemia. Arterioscler Thromb Vasc Biol 18 (1998), 1007–1012.
58. 58 Santos, PC, Morgan, AC, Jannes, CE, et al. Presence and type of low density lipoprotein receptor (LDLR) mutation influences the lipid profile and response to lipid-lowering therapy in Brazilian patients with heterozygous familial hypercholesterolemia. Atherosclerosis 233 (2014), 206–210.
59. 59 Gryn, SE, Hegele, RA, Pharmacogenomics, lipid disorders, and treatment options. Clin Pharmacol Ther 96 (2014), 36–47.
60. 60 Raal, FJ, Honarpour, N, Blom, DJ, et al., for the TESLA Investigators. Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double-blind, placebo-controlled trial. Lancet 385 (2015), 341–350.
61. 61 Ferrieres, J, Lambert, J, Lussier-Cacan, S, Davignon, J, Coronary artery disease in heterozygous familial hypercholesterolemia patients with the same LDL receptor gene mutation. Circulation 92 (1995), 290–295.
62. 62 Alonso, R, Andres, E, Mata, N, et al. Lipoprotein(a) levels in familial hypercholesterolemia: an important predictor of cardiovascular disease independent of the type of LDL receptor mutation. J Am Coll Cardiol 63 (2014), 1982–1989.
63. 63 Jansen, AC, van Aalst-Cohen, ES, Tanck, MW, et al. The contribution of classical risk factors to cardiovascular disease in familial hypercholesterolaemia: data in 2400 patients. J Intern Med 256 (2004), 482–490.
64. 64 Chan, DC, Pang, J, Hooper, AJ, et al. Elevated lipoprotein(a), hypertension and renal insufficiency as predictors of coronary artery disease in patients with genetically confirmed heterozygous familial hypercholesterolemia. Int J Cardiol 201 (2015), 633–638.
65. 65 Civeira, F, Castillo, S, Alonso, R, et al. Tendon xanthomas in familial hypercholesterolemia are associated with cardiovascular risk independently of the low-density lipoprotein receptor gene mutation. Arterioscler Thromb Vasc Biol 25 (2005), 1960–1965.
66. 66 Seed, M, Hoppichler, F, Reaveley, D, et al. Relation of serum lipoprotein(a) concentration and apolipoprotein(a) phenotype to coronary heart disease in patients with familial hypercholesterolemia. N Engl J Med 322 (1990), 1494–1499.
67. 67 Langsted, A, Kamstrup, PR, Benn, M, Tybjærg-Hansen, A, Nordestgaard, BG, High lipoprotein(a) as a possible cause of clinical familial hypercholesterolaemia: a prospective cohort study. Lancet Diabetes Endocrinol, 2016, 10.1016/S2213-8587(16)30042-0 published online May 12.
68. 68 Erqou, S, Kaptoge, S, Perry, PL, et al. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA 302 (2009), 412–423.
69. 69 Clarke, R, Peden, JF, Hopewell, JC, et al. Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N Engl J Med 361 (2009), 2518–2528.
70. 70 Kamstrup, PR, Tybjaerg-Hansen, A, Steffensen, R, Nordestgaard, BG, Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. JAMA 301 (2009), 2331–2339.
71. 71 Nordestgaard, BG, Chapman, MJ, Ray, K, et al. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur Heart J 31 (2010), 2844–2853.
72. 72 Santos, RD, Lipoprotein(a) and cardiovascular disease in heterozygous familial hypercholesterolemia: should we also blame the LDL receptor?. J Am Coll Cardiol 63 (2014), 1990–1991.
73. 73 Kraft, HG, Lingenhel, A, Raal, FJ, Hohenegger, M, Utermann, G, Lipoprotein(a) in homozygous familial hypercholesterolemia. Arterioscler Thromb Vasc Biol 20 (2000), 522–528.
74. 74 Romagnuolo, R, Scipione, CA, Boffa, MB, Marcovina, SM, Seidah, NG, Koschinsky, ML, Lipoprotein(a) catabolism is regulated by proprotein convertase subtilisin/kexin type 9 through the low density lipoprotein receptor. J Biol Chem 290 (2015), 11649–11662.
75. 75 Vongpromek, R, Bos, S, Ten Kate, GJ, et al. Lipoprotein(a) levels are associated with aortic valve calcification in asymptomatic patients with familial hypercholesterolaemia. J Intern Med 278 (2015), 166–173.
76. 76 Sijbrands, EJ, Nieman, K, Budoff, MJ, Cardiac computed tomography imaging in familial hypercholesterolaemia: implications for therapy and clinical trials. Curr Opin Lipidol 26 (2015), 586–592.
77. 77 McClelland, RL, Jorgensen, NW, Budoff, M, et al. 10-year coronary heart disease risk prediction using coronary artery calcium and traditional risk factors: derivation in the MESA (Multi-Ethnic Study of Atherosclerosis) with validation in the HNR (Heinz Nixdorf Recall) study and the DHS (Dallas Heart Study). J Am Coll Cardiol 66 (2015), 1643–1653.
78. 78 Georgiou, D, Budoff, MJ, Kaufer, E, Kennedy, JM, Lu, B, Brundage, BH, Screening patients with chest pain in the emergency department using electron beam tomography: a follow-up study. J Am Coll Cardiol 38 (2001), 105–110.
79. 79 Hadamitzky, M, Taubert, S, Deseive, S, et al. Prognostic value of coronary computed tomography angiography during 5 years of follow-up in patients with suspected coronary artery disease. Eur Heart J 34 (2013), 3277–3285.
80. 80 Chow, BJ, Small, G, Yam, Y, et al. Prognostic and therapeutic implications of statin and aspirin therapy in individuals with nonobstructive coronary artery disease: results from the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: an InteRnational Multicenter registry) registry. Arterioscler Thromb Vasc Biol 35 (2015), 981–989.
81. 81 Cheruvu, C, Precious, B, Naoum, C, et al. Long term prognostic utility of coronary CT angiography in patients with no modifiable coronary artery disease risk factors: results from the 5 year follow-up of the CONFIRM International Multicenter Registry. J Cardiovasc Comput Tomogr 10 (2016), 22–27.
82. 82 Gidding, SS, Bookstein, LC, Chomka, EV, Usefulness of electron beam tomography in adolescents and young adults with heterozygous familial hypercholesterolemia. Circulation 98 (1998), 2580–2583.
83. 83 Miname, MH, Ribeiro, MS II, Parga Filho, J, et al. Evaluation of subclinical atherosclerosis by computed tomography coronary angiography and its association with risk factors in familial hypercholesterolemia. Atherosclerosis 213 (2010), 486–491.
84. 84 Neefjes, LA, Ten Kate, GJ, Alexia, R, et al. Accelerated subclinical coronary atherosclerosis in patients with familial hypercholesterolemia. Atherosclerosis 219 (2011), 721–727.
85. 85 Santos, RD, Miname, MH, Martinez, LR, et al. Non-invasive detection of aortic and coronary atherosclerosis in homozygous familial hypercholesterolemia by 64 slice multi-detector row computed tomography angiography. Atherosclerosis 197 (2008), 910–915.
86. 86 The Multi-Ethnic Study of Atherosclerosis. Calcium calculator. http://www.mesa-nhlbi.org/calcium/input.aspx (accessed March 21, 2016).
87. 87 Santos, RD, Duell, PB, East, C, et al. Long-term efficacy and safety of mipomersen in patients with familial hypercholesterolaemia: 2-year interim results of an open-label extension. Eur Heart J 36 (2015), 566–575.
88. 88 Versmissen, J, Oosterveer, DM, Yazdanpanah, M, et al. Efficacy of statins in familial hypercholesterolaemia: a long term cohort study. BMJ, 337, 2008, a2423.
89. 89 Brown, WV, Brook, R, Hemphill, LC, Moriarty, PM, The use of lipopheresis in the practice of clinical lipidology. J Clin Lipidol 6 (2012), 98–104.
90. 90 Santos, RD, Watts, GF, Familial hypercholesterolaemia: PCSK9 inhibitors are coming. Lancet 385 (2015), 307–310.
91. 91 Thompson, GR, Barbir, M, Davies, D, et al. Efficacy criteria and cholesterol targets for LDL apheresis. Atherosclerosis 208 (2010), 317–321.
92. 92 Stefanutti, C, Vivenzio, A, Di Giacomo, S, Mazzarella, B, Bosco, G, Berni, A, Aorta and coronary angiographic follow-up of children with severe hypercholesterolemia treated with low-density lipoprotein apheresis. Transfusion 49 (2009), 1461–1470.
93. 93 Mabuchi, H, Koizumi, J, Shimizu, M, et al., for the Hokuriku-FH-LDL-Apheresis Study Group. Long-term efficacy of low-density lipoprotein apheresis on coronary heart disease in familial hypercholesterolemia. Am J Cardiol 82 (1998), 1489–1495.
94. 94 Somanathan, S, Jacobs, F, Wang, Q, Hanlon, AL, Wilson, JM, Rader, DJ, AAV vectors expressing LDLR gain-of-function variants demonstrate increased efficacy in mouse models of familial hypercholesterolemia. Circ Res 115 (2014), 591–599.
95. 95 Ramakrishnan, VM, Yang, JY, Tien, KT, et al. Restoration of physiologically responsive low-density lipoprotein receptor-mediated endocytosis in genetically deficient induced pluripotent stem cells. Sci Rep, 5, 2015, 13231.