Higher frequency of coronary atherosclerotic plaques in patients with genetically confirmed FH

An age-matched computed tomography angiographic study of coronary atherosclerotic plaques in patients with familial hypercholesterolaemia

Literature - Pang J, Abraham A, Vargas-García C et al., - Atherosclerosis. 2020. doi:10.1016/j.atherosclerosis.2020.03.001.

Introduction and methods

Familial hypercholesterolemia (FH) is characterized by elevated LDL-c levels and a high risk of premature coronary artery disease (CAD) [1]. There is, however, a wide variation of CAD prevalence in FH patients [2,3]. Coronary events in FH patients could potentially be predicted by coronary artery stenoses and coronary artery calcium (CAC) scoring on cardiac computed tomography angiography (CCTA) [4,5]. CCTA and CAC scoring may therefore play a role in risk assessment in FH patients [2, 6-8]. The present study investigated the frequency and distribution of coronary artery plaques in asymptomatic adult patients with a presumptive phenotypic FH diagnosis with and without genetically confirmed heterozygous FH.

Patients with asymptomatic phenotypic FH (Dutch Lipid Clinic Network [DLCN] category score of at least 3) were included in this aged-matched case-control study. Patients were managed according to expert guidelines [9], consented to genetic testing, and underwent CCTA and CAC scoring. From the total group of patients, 104 patients with genetically confirmed heterozygous FH (mutation-positive cases, M+) were randomly aged-matched 1:1 with 104 patients without a FH-causing mutation (mutation-negative controls, M-). Mean age was 49.9±10.4 years and 45.2% were male. The Society of Cardiovascular Computed Tomography guidelines were used to define calcific, non-calcific and mixed plaques [10]. CAC scores were semi-automatically calculated by the Agatston method [11]. The segment stenosis score (SSS) was calculated as the sum of scores attributed to each of the 19 coronary segments (0: no stenosis, 1: mild stenosis [<50%], 2: moderate stenosis [50-70%], 3: severe stenosis [>70%]) [12].

Main results

  • Pre-treatment LDL-c levels and phenotypic DLCN score were significantly higher in the M+ group compared to the M- group (LDL-c [mean±SD]: 7.8±2.1 vs 6.2±1.2 mmol/L, P<0.001 [adjusted for correlations within family clusters]; DLCN score: 11.2±4.5 vs 7.4±2.7, P<0.001).
  • A greater proportion of patients in the M+ group had mixed or calcified coronary plaques, compared to patients in the M- group (66.4% vs 50.0%, adjusted P-value=0.018 [adjusted for correlations within family clusters, age, gender, pre-treatment LDL-c levels, LP(a)>0.5 g/L and statin use]).
  • A higher proportion of patients with no plaques was observed in the M- group (23.1%) compared with the M+ group (10.6%; adjusted P-value=0.046).
  • Median CAC score and mean SSS were significantly higher in the M+ group, compared to the M- group (CAC score [median and IQR]: 33 [IQR 124] vs 0.25 [IQR 36], adjusted P-value=0.001; SSS [mean±SD]: 3.8±4.3 vs. 2.8±3.3, adjusted P-value=0.023).
  • There was a higher proportion of patients with calcification in the right coronary artery (RAD), Left main (LM) and left anterior descending (LAD) in the M+ group compared to the M- group (RAD: 39.4% vs 23.1%, adjusted P-value=0.015; LM: 27.9% vs 7.7%, adjusted P-value=0.001; LAD: 65.4% vs 40.4%, adjusted P-value=0.015). No significant differences between the two groups in the proportion of patients with calcification in other coronary artery segments were observed.
  • A higher proportion of patients in the M+ group had calcification in ≥2 vessels or ≥3 vessels, compared with the M- group (calcification in ≥2 vessels: 51.0% vs 36.5%, adjusted P-value=0.036; calcification in ≥3 vessels: 31.7% vs 16.4%, adjusted P-value=0.034).

Conclusion

Among asymptomatic adult patients with a presumptive phenotypic FH diagnosis, patients with a genetically confirmed diagnosis of FH had a higher frequency and severity of coronary atherosclerotic plaques, compared to patients without a FH-causing mutation.

References

1. G.F. Watts, S. Gidding, A.S. Wierzbicki, et al., Integrated guidance on the care of familial hypercholesterolaemia from the international FH foundation, Int. J. Cardiol. 171 (2014) 309–325.

2. F. Mach, C. Baigent, A.L. Catapano, et al., ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS), Eur. Heart J. 41 (2019) 111–188 2020.

3. R. Mszar, G.R. Grandhi, J. Valero-Elizondo, et al., Absence of coronary artery calcification in middle aged familial hypercholesterolemia patients without atherosclerotic cardiovascular disease, JACC (J. Am. Coll. Cardiol.): Cardiovascular Imaging (2019), https://doi.org/10.1016/j.jcmg.2019.11.001 In press.

4. H. Tada, M-a Kawashiri, H. Okada, et al., Assessment of coronary atherosclerosis in patients with familial hypercholesterolemia by coronary computed tomography angiography, Am. J. Cardiol. 115 (2015) 724–729.

5. M.H. Miname, M.S. Bittencourt, S.R. Moraes, et al., Coronary artery calcium and cardiovascular events in patients with familial hypercholesterolemia receiving standard lipid-lowering therapy, JACC (J. Am. Coll. Cardiol.): Cardiovascular Imaging 12 (2019) 1797–1804.

6. J. Knuuti, W. Wijns, A. Saraste, et al., ESC Guidelines for the diagnosis and management of chronic coronary syndromes, Eur. Heart J. 2019 (2019).

7. M.D. Miedema, Z.A. Dardari, K. Nasir, et al., Association of coronary artery calcium with long-term, cause-specific mortality among young adults, JAMA network open 2 (2019) e197440.

8. J. Patel, M. Al Rifai, M.J. Blaha, et al., Coronary artery calcium improves risk assessment in adults with a family history of premature coronary heart disease : results from multiethnic study of atherosclerosis, circulation, Cardiovascular Imaging 8 (2015) e003186.

9. G.F. Watts, D.R. Sullivan, N. Poplawski, et al., Familial hypercholesterolaemia: a model of care for Australasia, Atherosclerosis Suppl. 12 (2011) 221–263.

10. J. Leipsic, S. Abbara, S. Achenbach, et al., SCCT guidelines for the interpretation and reporting of coronary CT angiography: a report of the Society of Cardiovascular Computed Tomography Guidelines Committee, J Cardiovasc Comput Tomogr 8 (2014) 342–358.

11. A.S. Agatston, W.R. Janowitz, F.J. Hildner, et al., Quantification of coronary artery calcium using ultrafast computed tomography, J. Am. Coll. Cardiol. 15 (1990) 827–832.

12. J.K. Min, L.J. Shaw, R.B. Devereux, et al., Prognostic value of multidetector coronary computed tomographic angiography for prediction of all-cause mortality, J. Am. Coll. Cardiol. 50 (2007) 1161–1170.

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