- •A Web site (www.FHCanada.net), which provides information and resources for patients and health care professionals;
- •Better estimates of the prevalence of FH in Canada and the world1;
- •A new, simplified definition of FH specific to the Canadian context4;
- •A validated tool to calculate the baseline LDL-C during treatment with statins or ezetimibe5;
- •Diagnostic tools (http://www.circl.ubc.ca/cardiorisk-calculator.html) for health care professionals to make a precise diagnosis of FH;
- •Initial data from the FH Canada registry6; and
- •Genetic testing for FH in a Clinical Laboratory Improvement Amendments-certified laboratory.
Diagnosis of FH
- 1.We recommend that FH be defined using the DLCNC, Simon Broome Registry, or FH Canada definition (Strong Recommendation, High-Quality Evidence).
Screening for FH
- 2.We recommend that cascade screening (lipid profile) protocols be implemented at the local, provincial, and national level in Canada and offered to first-degree relatives of patients with FH (Strong Recommendation, Moderate-Quality Evidence).
- 3.We recommend that genetic testing be offered, when available, to complement a diagnosis of FH and enable cascade screening (Strong Recommendation, High-Quality Evidence).
ASCVD Risk and FH
ASCVD risk stratification in patients with FH: Genetics
ASCVD risk stratification in patients with FH: Clinical variables
ASCVD risk stratification in patients with FH: Imaging
- 4.We recommend that current risk calculators (Framingham Risk Score, Pooled Cohort Equation, European SCORE) should not be used to determine cardiovascular risk in patients with FH (Strong Recommendation, Low-Quality Evidence).
- 5.We suggest that if available, genetic testing should be used to stratify the ASCVD risk in patients with FH (Weak Recommendation, Moderate-Quality Evidence).
- 6.We suggest that conventional risk factors such as age, sex, HDL-C, hypertension, smoking, lipoprotein(a), and diabetes be ascertained in patients with FH (Weak Recommendation, Moderate-Quality Evidence).
Management of FH in Adults
Overall goals of treatment
- 7.We suggest that patients with FH adopt a healthy lifestyle as recommended by the CCS guidelines on the diagnosis and treatment of dyslipidemias9(Weak Recommendation, Low-Quality Evidence).
- 8.1.Because the diagnosis of FH using validated clinical criteria and/or genotyping may occur at any age and imparts a high, lifelong risk of ASCVD, we recommend a personalized treatment plan, taking into account, at a minimum, age, additional cardiovascular risk factors, psychosocial and socioeconomic factors, and personal as well as family preferences, that should be developed as a shared-decision process (Strong Recommendation, Low-Quality Evidence).
- 8.2.We recommend that for patients with FH requiring medications, a personalized treatment plan should include statins as the primary therapy and secondary agents as required, including ezetimibe and PCSK9 inhibitors according to the CCS guidelines on the diagnosis and treatment of dyslipidemias9(Strong Recommendation, Low-Quality Evidence).
- 9.In patients with FH and ASCVD, we suggest that targets should follow the recommendations of the CCS guidelines on the diagnosis and treatment of dyslipidemias9(LDL-C < 2.0 mmol/L and non–HDL-C < 2.6 mmol/L) (Weak Recommendation, Moderate-Quality Evidence).
- 10.We recommend that statins be used as the primary line of therapy (Strong Recommendation, High-Quality Evidence).
- 11.We suggest that ezetimibe be used as second-line agent to achieve unmet LDL-C goals (Weak Recommendation, Low-Quality Evidence).
- 12.We recommend that monoclonal antibody inhibitors of PCSK9 be considered in adult FH individuals without ASCVD if they have not achieved a 50% reduction in LDL-C from baseline level and reached an LDL-C level of at least < 3.5 mmol/L or lower (as determined by the shared decision process between physician and patient) on maximally tolerated statin therapy with or without ezetimibe, as per recommendation 8 (Strong Recommendation, High-Quality of Evidence).
- Cuchel M.
- Bruckert E.
- Ginsberg H.N.
- et al.
- Drouin-Chartier J.P.
- Tremblay A.J.
- Bergeron J.
- Lamarche B.
- Couture P.
Pregnancy in FH
- 13.We recommend that statins should not be used during pregnancy (Strong Recommendation, Low-Quality Evidence).
Type 2 diabetes mellitus in patients with FH
- Cuchel M.
- Bruckert E.
- Ginsberg H.N.
- et al.
- Cuchel M.
- Bruckert E.
- Ginsberg H.N.
- et al.
- 14.We recommend that patients with HoFH be referred to a specialized lipid clinic and undergo complete evaluation for genetic analysis, presence of ASCVD, and aggressive lipid-lowering therapies, including consideration for extracorporeal LDL-C removal, lomitapide, and PCSK9 inhibitors (Strong Recommendation, Moderate-Quality Evidence).
Screening and diagnosis
- 15.We suggest that universal cholesterol level screening be considered for detection of FH in children with reverse cascade screening of parents when warranted (Weak Recommendation, Moderate-Quality Evidence).
- 16.We suggest that statin therapy be considered usually between 8 and 10 years of age if LDL-C remains ≥ 4.9 mmol/L, or ≥ 4.1 mmol/L with a family history of premature ASCVD or other cardiovascular risk factors or risk conditions (Weak Recommendation, Moderate-Quality Evidence).
Cascade Screening, FH Registry, Knowledge Translation
- 17.We recommend that a national registry for FH be implemented to raise awareness among patients and health care professionals and to provide advocacy to ensure access to effective therapies (Strong Recommendation, Moderate-Quality Evidence).
- Supplementary Material
- Estimating the prevalence of heterozygous familial hypercholesterolaemia: a systematic review and meta-analysis.BMJ Open. 2017; 7e016461
- 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: 3478-3490a
- Canadian Cardiovascular Society position statement on familial hypercholesterolemia.Can J Cardiol. 2014; 30: 1471-1481
- Simplified Canadian definition for familial hypercholesterolemia.Can J Cardiol. 2018; 34: 1210-1214
- Imputation of baseline LDL cholesterol concentration in patients with familial hypercholesterolemia on statins or ezetimibe.Clin Chem. 2018; 64: 355-362
- Familial hypercholesterolemia in Canada: initial results from the FH Canada National Registry.Atherosclerosis. 2018; 277: 419-424
- US physician practices for diagnosing familial hypercholesterolemia: data from the CASCADE-FH registry.J Clin Lipidol. 2016; 10: 1223-1229
- 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
- 2016 Canadian Cardiovascular Society guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult.Can J Cardiol. 2016; 32: 1263-1282
- Cascade screening for familial hypercholesterolemia and the use of genetic testing.JAMA. 2017; 318: 381-382
- Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment.Eur Heart J. 2015; 36: 2425-2437
- Genetically confirmed familial hypercholesterolemia in patients with acute coronary syndrome.J Am Coll Cardiol. 2017; 70: 1732-1740
- Genetic identification of familial hypercholesterolemia within a single U.S. health care system.Science. 2016; 354: aaf7000
- Diagnostic yield and clinical utility of sequencing familial hypercholesterolemia genes in patients with severe hypercholesterolemia.J Am Coll Cardiol. 2016; 67: 2578-2589
- Child-parent familial hypercholesterolemia screening in primary care.N Engl J Med. 2016; 375: 1628-1637
- Polygenic versus monogenic causes of hypercholesterolemia ascertained clinically.Arterioscler Thromb Vasc Biol. 2016; 36: 2439-2445
- Selection of individuals for genetic testing for familial hypercholesterolaemia: development and external validation of a prediction model for the presence of a mutation causing familial hypercholesterolaemia.Eur Heart J. 2017; 38: 565-573
- 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. 2015; 61: 231-238
- 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
- Impact of clinical signs and genetic diagnosis of familial hypercholesterolaemia on the prevalence of coronary artery disease in patients with severe hypercholesterolaemia.Eur Heart J. 2017; 38: 1573-1579
- The agenda for familial hypercholesterolemia: a scientific statement from the American Heart Association.Circulation. 2015; 132: 2167-2192
- Defining severe familial hypercholesterolaemia and the implications for clinical management: a consensus statement from the International Atherosclerosis Society Severe Familial Hypercholesterolemia Panel.Lancet Diabetes Endocrinol. 2016; 4: 850-861
- National Institutes for Clinical Excellence. Familial Hypercholesterolaemia: Identification and Management.(Available at:)Accessed May 8, 2018)
- Clinical genetic testing for familial hypercholesterolemia: JACC Scientific Expert Panel.J Am Coll Cardiol. 2018; 72: 662-680
- Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics.Genet Med. 2017; 19: 249-255
- Statins in familial hypercholesterolemia: consequences for coronary artery disease and all-cause mortality.J Am Coll Cardiol. 2016; 68: 252-260
- Cardiovascular disease in familial hypercholesterolemia: validation and refinement of the Montreal-FH-SCORE.J Clin Lipidol. 2017; 11: 1161-1167
- Severe heterozygous familial hypercholesterolemia and risk for cardiovascular disease: a study of a cohort of 14,000 mutation carriers.Atherosclerosis. 2014; 233: 219-223
- Carotid artery plaques and intima medial thickness in familial hypercholesteraemic patients on long-term statin therapy: a case control study.Atherosclerosis. 2017; 256: 62-66
- Efficacy of statins in familial hypercholesterolaemia: a long term cohort study.BMJ. 2008; 337: a2423
- Effect of rosuvastatin on carotid intima-media thickness in children with heterozygous familial hypercholesterolemia: the CHARON study (Hypercholesterolemia in Children and Adolescents Taking Rosuvastatin Open Label).Circulation. 2017; 136: 359-366
- ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia.Eur Heart J. 2015; 36: 2996-3003
- Long-term safety, tolerability, and efficacy of evolocumab in patients with heterozygous familial hypercholesterolemia.J Clin Lipidol. 2017; 11: 1448-1457
- Attainment of recommended lipid targets in patients with familial hypercholesterolemia: real-world experience with PCSK9 inhibitors.Can J Cardiol. 2018; 34: 1004-1009
- Evolocumab and clinical outcomes in patients with cardiovascular disease.N Engl J Med. 2017; 376: 1713-1722
- Effect of alirocumab, a monoclonal antibody to PCSK9, on long-term cardiovascular outcomes following acute coronary syndromes: rationale and design of the ODYSSEY outcomes trial.Am Heart J. 2014; 168: 682-689
- Cardiovascular event reduction with PCSK9 inhibition among 1578 patients with familial hypercholesterolemia: results from the SPIRE randomized trials of bococizumab.J Clin Lipidol. 2018; 12: 958-965
- 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. 2014; 35: 2146-2157
- The low-density lipoprotein receptor genotype is a significant determinant of the rebound in low-density lipoprotein cholesterol concentration after lipoprotein apheresis among patients with homozygous familial hypercholesterolemia.Circulation. 2017; 136: 880-882
- The fetal safety of statins: a systematic review and meta-analysis.J Obstet Gynaecol Can. 2014; 36: 506-509
- Statins and congenital malformations: cohort study.BMJ. 2015; 350: h1035
- Association between familial hypercholesterolemia and prevalence of type 2 diabetes mellitus.JAMA. 2015; 313: 1029-1036
- Universal versus targeted blood cholesterol screening among youth: the CARDIAC project.Pediatrics. 2010; 126: 260-265
- Statins for children with familial hypercholesterolemia.Cochrane Database Syst Rev. 2017; 7: CD006401
The disclosure information of the authors and reviewers is available from the CCS on their guidelines library at www.ccs.ca.
This statement was developed following a thorough consideration of medical literature and the best available evidence and clinical experience. It represents the consensus of a Canadian panel comprised of multidisciplinary experts on this topic with a mandate to formulate disease-specific recommendations. These recommendations are aimed to provide a reasonable and practical approach to care for specialists and allied health professionals obliged with the duty of bestowing optimal care to patients and families, and can be subject to change as scientific knowledge and technology advance and as practice patterns evolve. The statement is not intended to be a substitute for physicians using their individual judgement in managing clinical care in consultation with the patient, with appropriate regard to all the individual circumstances of the patient, diagnostic and treatment options available and available resources. Adherence to these recommendations will not necessarily produce successful outcomes in every case.