Atherosclerosis xxx (2015) 1e3
Contents lists available at ScienceDirect
Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis
Invited commentary
Europe aspires to set the record straight on familial hypercholesterolaemia Gerald F. Watts a, b, *, Jing Pang a, Raul D. Santos c a
School of Medicine and Pharmacology, University of Western Australia, Western Australia, Australia Lipid Disorders Clinic, Cardiovascular Medicine, Royal Perth Hospital, Western Australia, Australia c ~o Paulo Medical School Hospital, and Preventive Medicine Centre and Cardiology Program Hospital Lipid Clinic Heart Institute (InCor), University of Sa ~o Paulo, Brazil Israelita Albert Einstein, Sa b
a r t i c l e i n f o Article history: Received 13 April 2015 Accepted 14 April 2015 Available online xxx Keywords: Familial hypercholesterolaemia Screening Coronary care unit Prevalence
1. Editorial Familial hypercholesterolaemia (FH) is a co-dominantly inherited condition that markedly elevates plasma levels of low-density lipoprotein (LDL) cholesterol and induces premature coronary artery disease (CAD) [1]. Risk of CAD in FH may be significantly diminished through early detection and treatment of hypercholesterolaemia [1e3]. However, FH remains under-detected and under-treated worldwide [2]. International guidelines recommend diverse screening strategies for FH, a potentially highly effective one being identification of index cases among patients with early CAD, with subsequent cascade testing of family members [1,2]. The frequency and management of FH among patients with CAD has not, however, been adequately documented and requires further evaluation to inform future planning and policy for the care of FH. The EUROASPIRE-IV Investigators tested the prevalence of FH using modified Dutch Lipid Clinic Network Criteria (DLCNC) in 7044 patients (male:female ratio ¼ 3.12:1) aged 18e80 years with CAD in 24 countries in Europe [4]. The age-standardized prevalence of
* Corresponding author. GPO Box X2213, Perth, WA 6847, Australia. E-mail address: [email protected] (G.F. Watts).
probable/definite FH was 8.3% and 20% among those aged less than 50 years. Overall, FH was apparently more common in women than men (11.1% vs 7.5%). There was wide variation in the prevalence of FH among countries, the lowest in Finland (3.4%) and the highest in Bosnia Herzegovina (20.8%). The prevalence of non-cholesterol CAD risk factors was high, with smoking, low HDL-cholesterol and high triglyceride being significantly more common in patients with FH than those without FH. Blood pressure and diabetes were not well controlled in about 40% of the FH patients and 25% were still smoking. High intensity statins were used by only 55% of the FH patients, but a greater proportion were taking aspirin and beta blockers (90%) and angiotensin-converting-enzyme inhibitors or angiotensin II receptor blockers (75%). These data emphasize that FH is common among CAD patients and foreshadow the major challenges facing the management of such patients in Europe and, by extension, the rest of the world. How accurate and representative are these data of the status of FH in Europe? The use of a ‘probable’ definition FH by the DLCNC could have over-inflated the frequency of the condition, noting that the prevalence of ‘definite’ FH was 1.1%. Adjustment of plasma LDL cholesterol for statins might have also contributed to error in the diagnosis and misclassified patients [5], acknowledging the wide inter-individual variability in the response to statins [6]. Whole exome sequencing of patients with premature CAD shows that only 2% have LDL receptor mutations [7]. Since genetic testing for FH was not undertaken in EUROASPIRE-IV, it is possible that a significant proportion of individuals had hereditary elevation of liporotein(a) [8] and/or familial combined hyperlipidaemia [9]. The latter accords with the high prevalence of obesity, diabetes and hypertriglyceridemia in the FH cohort. Recent evidence shows that polygenic hypercholesterolaemia can mimic FH, but can be distinguished from it by a high ‘cholesterol gene score’ [10] relating to high frequency, small effect size cholesterol raising alleles. Finally, the possibility of recurrent fatal myocardial infarction in the period of assessment between six months to three years after the first coronary event might have excluded more patients with FH, especially men, and could have led to an underestimation of the prevalence of the condition [4].
http://dx.doi.org/10.1016/j.atherosclerosis.2015.04.016 0021-9150/© 2015 Published by Elsevier Ireland Ltd.
Please cite this article in press as: G.F. Watts, et al., Europe aspires to set the record straight on familial hypercholesterolaemia, Atherosclerosis (2015), http://dx.doi.org/10.1016/j.atherosclerosis.2015.04.016
2
G.F. Watts et al. / Atherosclerosis xxx (2015) 1e3
Table 1 Published data on the prevalence of FH in individuals with early onset CAD and in the EUROASPIRE-IV study. First author, year
Country/Region
n
Age
Prevalence
Diagnostic test
Patterson, 1972 [11] Goldstein, 1973 [12] Nikkila, 1973 [13] Koivisto, 1993 [14] Dorsch, 2001 [15] Bates, 2008 [16] Rallidis, 2008 [17] Wiesbauer, 2009 [18] Yudi, 2012 [19] Wald, 2015 [20] De Backer, 2015 [4]
United Kingdom USA Finland Finland United Kingdom Australia Greece Austria Australia United Kingdom Europe
193 1450 775 150 292 199 135 302 201 231 7044 2212
Contents lists available at ScienceDirect
Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis
Invited commentary
Europe aspires to set the record straight on familial hypercholesterolaemia Gerald F. Watts a, b, *, Jing Pang a, Raul D. Santos c a
School of Medicine and Pharmacology, University of Western Australia, Western Australia, Australia Lipid Disorders Clinic, Cardiovascular Medicine, Royal Perth Hospital, Western Australia, Australia c ~o Paulo Medical School Hospital, and Preventive Medicine Centre and Cardiology Program Hospital Lipid Clinic Heart Institute (InCor), University of Sa ~o Paulo, Brazil Israelita Albert Einstein, Sa b
a r t i c l e i n f o Article history: Received 13 April 2015 Accepted 14 April 2015 Available online xxx Keywords: Familial hypercholesterolaemia Screening Coronary care unit Prevalence
1. Editorial Familial hypercholesterolaemia (FH) is a co-dominantly inherited condition that markedly elevates plasma levels of low-density lipoprotein (LDL) cholesterol and induces premature coronary artery disease (CAD) [1]. Risk of CAD in FH may be significantly diminished through early detection and treatment of hypercholesterolaemia [1e3]. However, FH remains under-detected and under-treated worldwide [2]. International guidelines recommend diverse screening strategies for FH, a potentially highly effective one being identification of index cases among patients with early CAD, with subsequent cascade testing of family members [1,2]. The frequency and management of FH among patients with CAD has not, however, been adequately documented and requires further evaluation to inform future planning and policy for the care of FH. The EUROASPIRE-IV Investigators tested the prevalence of FH using modified Dutch Lipid Clinic Network Criteria (DLCNC) in 7044 patients (male:female ratio ¼ 3.12:1) aged 18e80 years with CAD in 24 countries in Europe [4]. The age-standardized prevalence of
* Corresponding author. GPO Box X2213, Perth, WA 6847, Australia. E-mail address: [email protected] (G.F. Watts).
probable/definite FH was 8.3% and 20% among those aged less than 50 years. Overall, FH was apparently more common in women than men (11.1% vs 7.5%). There was wide variation in the prevalence of FH among countries, the lowest in Finland (3.4%) and the highest in Bosnia Herzegovina (20.8%). The prevalence of non-cholesterol CAD risk factors was high, with smoking, low HDL-cholesterol and high triglyceride being significantly more common in patients with FH than those without FH. Blood pressure and diabetes were not well controlled in about 40% of the FH patients and 25% were still smoking. High intensity statins were used by only 55% of the FH patients, but a greater proportion were taking aspirin and beta blockers (90%) and angiotensin-converting-enzyme inhibitors or angiotensin II receptor blockers (75%). These data emphasize that FH is common among CAD patients and foreshadow the major challenges facing the management of such patients in Europe and, by extension, the rest of the world. How accurate and representative are these data of the status of FH in Europe? The use of a ‘probable’ definition FH by the DLCNC could have over-inflated the frequency of the condition, noting that the prevalence of ‘definite’ FH was 1.1%. Adjustment of plasma LDL cholesterol for statins might have also contributed to error in the diagnosis and misclassified patients [5], acknowledging the wide inter-individual variability in the response to statins [6]. Whole exome sequencing of patients with premature CAD shows that only 2% have LDL receptor mutations [7]. Since genetic testing for FH was not undertaken in EUROASPIRE-IV, it is possible that a significant proportion of individuals had hereditary elevation of liporotein(a) [8] and/or familial combined hyperlipidaemia [9]. The latter accords with the high prevalence of obesity, diabetes and hypertriglyceridemia in the FH cohort. Recent evidence shows that polygenic hypercholesterolaemia can mimic FH, but can be distinguished from it by a high ‘cholesterol gene score’ [10] relating to high frequency, small effect size cholesterol raising alleles. Finally, the possibility of recurrent fatal myocardial infarction in the period of assessment between six months to three years after the first coronary event might have excluded more patients with FH, especially men, and could have led to an underestimation of the prevalence of the condition [4].
http://dx.doi.org/10.1016/j.atherosclerosis.2015.04.016 0021-9150/© 2015 Published by Elsevier Ireland Ltd.
Please cite this article in press as: G.F. Watts, et al., Europe aspires to set the record straight on familial hypercholesterolaemia, Atherosclerosis (2015), http://dx.doi.org/10.1016/j.atherosclerosis.2015.04.016
2
G.F. Watts et al. / Atherosclerosis xxx (2015) 1e3
Table 1 Published data on the prevalence of FH in individuals with early onset CAD and in the EUROASPIRE-IV study. First author, year
Country/Region
n
Age
Prevalence
Diagnostic test
Patterson, 1972 [11] Goldstein, 1973 [12] Nikkila, 1973 [13] Koivisto, 1993 [14] Dorsch, 2001 [15] Bates, 2008 [16] Rallidis, 2008 [17] Wiesbauer, 2009 [18] Yudi, 2012 [19] Wald, 2015 [20] De Backer, 2015 [4]
United Kingdom USA Finland Finland United Kingdom Australia Greece Austria Australia United Kingdom Europe
193 1450 775 150 292 199 135 302 201 231 7044 2212
