Prevalence and clinical characteristics of familial hypercholesterolemia phenotypes in patients with acute coronary syndrome: data from the prospective observational registry study of patients with acute coronary syndrome (PRIMA-ACS)

Data on the prevalence and clinical features of familial hypercholesterolemia (FH) in the cohort of patients with acute coronary syndrome (ACS) are few and of particular interest due to the high risk of recurrent cardiovascular events. The aim of the study was to analyze the prevalence and evaluate the clinical parameters of patients with phenotypic FH among ACS patients with an assessment of the development of recurrent cardiovascular events.

Material and methods. The study included 498 patients hospitalized for the development of ACS. The clinical probability of FH was assessed using the diagnostic criteria of the Dutch Lipid Clinics (DLCN score). The follow-up lasted for one year.

Results. A possible diagnosis of FH was determined in 86 (17.3 %) patients, and a probable diagnosis of FH was determined in 6 (1.2 %) patients. Compared with the group of patients without clinical FH, patients with possible and probable FH were characterized by younger age (68.5 years versus 59.5 and 50.5 years, p < 0.001), higher incidence of family history of premature cardiovascular diseases (CVDs) (22.9 % versus 77.9 % and 83.3 %, p < 0.001) and earlier personal history of CVDs (24.1 % versus 90.7 and 100 %, p < 0.001). Patients with FH had more significant abnormalities of lipid metabolism: level of total serum cholesterol and low-density lipoprotein cholesterol was significantly higher among patients with possible and probable FH (p < 0.001) compared to patients without FH. There were no statistically significant differences in the development of cardiovascular events during hospitalization and in the first year after hospital discharge (p > 0.05).

Conclusions. A high prevalence of clinical FH in the population of ACS patients has been revealed. Patients with FH are characterized by younger age, high frequency of family history of premature CVD, early personal history of CVD and more significant lipid disorders. The obtained data demonstrate the importance of identifying patients with FH in order to intensify lipid-lowering therapy to reduce atherogenic burden and prevent the development of acute primary and recurrent cardiovascular events.

1. Foody J.M. Familial hypercholesterolemia: an under-recognized but significant concern in cardiology practice. Clin. Cardiol., 2014; 37 (2): 119–125. doi: 10.1002/clc.22223

2. Singh A., Gupta A., Collins B.L., Qamar A., Monda K.L., Biery D., Lopez J.A.G., de Ferranti S.D., Plutzky J., Cannon C.P., Januzzi J.L.Jr., di Carli M.F., Nasir K., Bhatt D.L., Blankstein R. Familial hypercholesterolemia among young adults with myocardial infarction. J. Am. Coll. Cardiol., 2019; 73 (19): 2439–2450. doi: 10.1016/j.jacc.2019.02.059

3. Amor-Salamanca A., Castillo S., Gonzalez-Vioque E., Dominguez F., Quintana L., Lluís-Ganella C., Escudier J.M., Ortega J., Lara-Pezzi E., Alonso-Pulpon L., Garcia-Pavia P. Genetically Confirmed Familial Hypercholesterolemia in Patients With Acute Coronary Syndrome. J. Am. Coll. Cardiol., 2017 Oct 3; 70 (14): 1732–1740. doi: 10.1016/j.jacc.2017.08.009

4. de Backer G., Besseling J., Chapman J., Hovingh G.K., Kastelein J.J., Kotseva K., Ray K., Reiner Ž., Wood D., de Bacquer D.; EUROASPIRE Investigators. Prevalence and management of familial hypercholesterolaemia in coronary patients: An analysis of EUROASPIRE IV, a study of the European Society of Cardiology. Atherosclerosis, 2015 Jul; 241 (1): 169–175. doi: 10.1016/j.atherosclerosis.2015.04.809

5. Dyrbuś K., Gąsior M., Desperak P., Osadnik T., Nowak J., Banach M. The prevalence and management of familial hypercholesterolemia in patients with acute coronary syndrome in the Polish tertiary centre: Results from the TERCET registry with 19,781 individuals. Atherosclerosis, 2019 Sep; 288: 33–41. doi: 10.1016/j.atherosclerosis.2019.06.899

6. Nordestgaard B.G., Chapman M.J., Humphries S.E., Ginsberg H.N., Masana L., Descamps O.S., Wiklund O., Hegele R.A., Raal F.J., Defesche J.C., Wiegman A., Santos R.D., Watts G.F., Parhofer K.G., Hovingh G.K., Kovanen P.T., Boileau C., Averna M., Borén J., Bruckert E., Catapano A.L., Kuivenhoven J.A., Pajukanta P., Ray K., Stalenhoef A.F., Stroes E., Taskinen M.R., Tybjærg-Hansen A.; European Atherosclerosis Society Consensus Panel. 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 Dec; 34 (45): 3478–3490a. doi: 10.1093/eurheartj/eht273

7. Научно-организационный комитет проекта ЭССЕРФ. Эпидемиология сердечно-сосудистых заболеваний в различных регионах России (ЭССЕ-РФ). Обоснование и дизайн исследования. Профилакт. медицина. 2013; 16 (6): 25–34.

8. Stein J.H., Korcarz C.E., Hurst R.T., Lonn E., Kendall C.B., Mohler E.R., Najjar S.S., Rembold C.M., Post W.S.; American Society of Echocardiography Carotid Intima-Media Thickness Task Force. Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: a consensus statement from the American Society of Echocardiography Carotid Intima-Media Thickness Task Force. Endorsed by the Society for Vascular Medicine. J. Am. Soc. Echocardiogr., 2008 Feb; 21 (2): 93– 111; quiz 189–190. doi: 10.1016/j.echo.2007.11.011

9. Ежов М.В., Близнюк С.А., Сагайдак О.В., Выгодин В.А., Чубыкина У.В., Колмакова Т.Е., Ощепкова Е.В. Возможность выявления семейной гиперхолестеринемии при остром коронарном синдроме (по данным федерального регистра острого коронарного синдрома). Кардиол. вестн., 2019; 4. doi: 10.36396/MS.2019.15.4.006

10. Nanchen D., Gencer B., Auer R., Räber L., Stefanini G.G., Klingenberg R., Schmied C.M., Cornuz J., Muller O., Vogt P., Jüni P., Matter C.M., Windec- ker S., Lüscher T.F., Mach F., Rodondi N. Prevalence and management of familial hypercholesterolaemia in patients with acute coronary syndromes. Eur Heart J., 2015 Sep 21; 36 (36): 2438–2445. doi: 10.1093/eurheartj/ehv289

11. Al-Rasadi K., Al-Zakwani I., Alsheikh-Ali A.A., Almahmeed W., Rashed W., Ridha M., Santos R.D., Zubaid M. Prevalence, management, and outcomes of familial hypercholesterolemia in patients with acute coronary syndromes in the Arabian Gulf. J. Clin. Lipidol., 2018 May-Jun; 12 (3): 685–692.e2. doi: 10.1016/j.jacl.2018.02.003

12. Rallidis L.S., Triantafyllis A.S., Tsirebolos G., Katsaras D., Rallidi M., Moutsatsou P., Lekakis J. Prevalence of heterozygous familial hypercholesterolaemia and its impact on long-term prognosis in patients with very early ST-segment elevation myocardial infarction in the era of statins. Atherosclerosis, 2016 Jun; 249: 17–21. doi: 10.1016/j.atherosclerosis.2016.03.023

13. Kheiri B., Simpson T.F., Osman M., Balla S., Rahmouni H., Mehta A., Pokharel Y., Nasir K., Fazio S., Shapiro M.D. Familial hypercholesterolemia related admission for acute coronary syndrome in the United States: Incidence, predictors, and outcomes. J. Clin. Lipidol., 2021 May-Jun; 15 (3): 460–465. doi: 10.1016/j.jacl.2021.04.005

14. Nanchen D., Gencer B., Muller O., Auer R., Aghlmandi S., Heg D., Klingenberg R., Räber L., Carballo D., Carballo S., Matter C.M., Lüscher T.F., Windecker S., Mach F., Rodondi N. Prognosis of Patients With Familial Hypercholesterolemia After Acute Coronary Syndromes. Circulation, 2016 Sep 6; 134 (10): 698–709. doi: 10.1161/CIRCULATIONAHA.116.023007

15. Benedek P., Eriksson M., Duvefelt K., Freyschuss A., Frick M., Lundman P., Nylund L., Szummer K. Genetic testing for familial hypercholesterolemia among survivors of acute coronary syndrome. J. Intern. Med., 2018 Dec; 284 (6): 674–684. doi: 10.1111/joim.12812