Highlights
- •Familial hypercholesterolemia (FH) is a major risk factor for premature and subsequent cardiovascular disease.
- •Data on long-term major adverse cardiovascular events in patients with FH after coronary stenting are scarce.
- •5.0% were classified with probable/definite FH.
- •Mean follow-up was 6.0 ± 2.4 years.
- •Probable/definite FH was associated with a 1.9-fold increased risk for MACE.
Background
Patients with familial hypercholesterolemia (FH) are at increased risk for premature
and subsequent cardiovascular disease. Data on long-term major adverse cardiovascular
events (MACE) in patients with FH after percutaneous coronary intervention (PCI) in
the era of high-intensity statins are scarce.
Objective
We assessed the prognostic impact of clinically diagnosed FH on long-term MACE, a
composite of all-cause death, myocardial infarction, and ischemic stroke in patients
admitted for stable coronary artery disease (SCAD) or acute coronary syndromes (ACSs)
undergoing PCI.
Methods
FH was diagnosed according to the Dutch Lipid Clinic Network diagnosis criteria: “Unlikely
FH” diagnosis was defined as 0 to 2 points, “possible FH” as 3 to 5 points, and “probable/definite
FH” diagnosis as 6 or higher.
Results
From a total of 1550 eligible patients (47.4% were admitted for SCAD and 52.6% for
ACS), 77 (5.0%) were classified as probable/definite FH, 332 (21.4%) as possible FH,
and 1141 (73.6%) as unlikely FH. Mean follow-up was 6.0 ± 2.4 years. After adjustment
for possible confounders, patients classified with probable or definite FH (hazard
ratio [HR] 1.922 [95% confidence interval (CI) 1.220–2.999]; P = .004), but not patients with possible FH (HR 1.105 [95% CI 0.843–1.447]; P = .470) faced a significant, approximately 2-fold increased risk of MACE compared
with patients with unlikely FH.
Conclusion
After adjustment for confounders, patients with probable or definite FH faced an approximate
2-fold increased risk for long-term MACE compared with patients without FH despite
the widespread use of high-intensity statins. The new option of proprotein convertase
subtilisin/kexin type 9 gene inhibitors in addition to other current optimal lipid-lowering
strategies might help to further improve clinical outcome in patients with probable/definite
FH.
Keywords
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References
- 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. 2013; 34: 3478-3490
- Familial Hypercholesterolemia: A Genetic Defect in the Low-Density Lipoprotein Receptor.N Engl J Med. 1976; 294: 1386-1390
- Genetic heterogeneity of autosomal dominant hypercholesterolemia.Clin Genet. 2008; 73: 1-13
- Familial hypercholesterolemia: screening, diagnosis and management of pediatric and adult patients: clinical guidance from the national lipid association expert panel on familial hypercholesterolemia.J Clin Lipidol. 2011; 5: S1-S8
- Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment.Eur Heart J. 2015; 36: 2425-2437
- Efficacy of statins in familial hypercholesterolaemia: a long term cohort study.BMJ. 2008; 337: a2423
- Attainment of LDL-cholesterol treatment goals in patients with familial hypercholesterolemia: 5-year safeheart registry follow-up.J Am Coll Cardiol. 2016; 67: 1278-1285
- Prevalence and management of familial hypercholesterolaemia in patients with acute coronary syndromes.Eur Heart J. 2015; 36: 2438-2445
- Prevalence and management of familial hypercholesterolaemia in coronary patients: An analysis of EUROASPIRE IV, a study of the European Society of Cardiology.Atherosclerosis. 2015; 241: 169-175
- Mutations causative of familial hypercholesterolaemia: screening of 98 098 individuals from the Copenhagen General Population Study estimated a prevalence of 1 in 217.Eur Heart J. 2016; 37: 1384-1394
- Prevalence and management of familial hypercholesterolemia in patients with coronary artery disease: The heredity survey.Int J Cardiol. 2018; 252: 193-198
- Prognosis of patients with familial hypercholesterolemia after acute coronary syndromesclinical perspective.Circulation. 2016; 134: 698-709
- Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation: the Task Force on the Management of ST-Segment Elevation Acute Myocardial Infarction of the European Society of Cardiology.Eur Heart J. 2008; 29: 2909-2945
- Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes: The Task Force for the Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coronary Syndromes of the European Society of Cardiology.Eur Heart J. 2007; 28: 1598-1660
- Familial hypercholesterolaemia (FH): report of a second WHO consultation, Geneva, 4 September 1998.World Health Organisation, 1999 (Available at:) (Accessed October 13, 2018)
- Severe heterozygous familial hypercholesterolemia and risk for cardiovascular disease: A study of a cohort of 14,000 mutation carriers.Atherosclerosis. 2014; 233: 219-223
- The prevalence and prognostic importance of possible familial hypercholesterolemia in patients with myocardial infarction.Am Heart J. 2016; 181: 35-42
- Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge.Clin Chem. 1972; 18: 499-502
- Augmented backward elimination: a pragmatic and purposeful way to develop statistical models.PLoS One. 2014; 9: e113677
- A new equation to estimate glomerular filtration rate.Ann Intern Med. 2009; 150: 604-612
- ESC/EAS Guidelines for the Management of Dyslipidaemias.Eur Heart J. 2016; 37: 2999-3058
- Statins in Familial Hypercholesterolemia.J Am Coll Cardiol. 2016; 68: 252-260
- Evolocumab and clinical outcomes in patients with cardiovascular disease.N Engl J Med. 2017; 376: 1713-1722
- Genetically confirmed familial hypercholesterolemia in patients with acute coronary syndrome.J Am Coll Cardiol. 2017; 70: 1732-1740
- Evaluation of clinical and laboratory parameters used in the identification of index cases for genetic screening of familial hypercholesterolemia in Brazil.Atherosclerosis. 2017; 263: 257-262
Article Info
Publication History
Published online: September 21, 2018
Accepted:
September 18,
2018
Received:
April 5,
2018
Footnotes
Conflicts of Interest: K.H. received lecture fees from AMGEN and SANOFI AVENTIS. The rest of the authors declare no conflicts of interest.
Identification
Copyright
© 2018 National Lipid Association. All rights reserved.
