Dear Editor,
In their comprehensive review articleCitation1, Anagnostis et al. discuss the association between familial hypercholesterolaemia (FH) and the risk of non-coronary atherosclerotic vascular disease, namely carotid artery stenosis, stroke, peripheral artery disease (PAD) and aortic/renal artery diseaseCitation1.
FH is a common autosomal dominant inherited disease affecting one in 200–500 individuals worldwideCitation1. Hypercholesterolaemia is a major risk factor for the development of atherosclerotic non-coronary vascular diseaseCitation2,Citation3. Thus, patients with (often undiagnosed) FH are at increased risk of developing advanced atherosclerotic disease prematurely in at least one vascular bed. A recent large cohort study from the UK (n = 14,097 patients with vs 42,506 patients without FH) demonstrated a >7-fold higher risk of PAD (hazard ratio [HR]: 7.17; 95% confidence interval [CI]: 6.08–8.46; p < .001) and a nearly 7-fold higher risk of stroke/transient ischaemic attack (TIA; HR: 6.74; 95% CI: 5.84–7.77; p < .001) in patients with vs without FHCitation4. Importantly, the overall mean age at first diagnosis of PAD and stroke/TIA was approximately 10 years earlier in patients with compared with those without FH (52.4 ± 8.2 vs 61.7 ± 10.9 and 51.9 ± 8.5 vs 63.7 ± 11.2 years, respectively; p < .0001 for both associations)Citation4. Therefore, vascular surgeons/vascular specialists should keep in mind that patients with FH present with advanced forms of PAD and carotid stenosis much earlier than the general population. Furthermore, when FH is combined with other vascular risk factors (e.g. smoking or diabetes mellitus), the risk of developing advanced vascular disease prematurely would probably be even higher.
Another important issue is that when patients with FH are undergoing a vascular surgical procedure, their long-term outcomes are considerably worse compared with the general population. A study comparing long-term prognosis in patients with vs without FH after a coronary event is relevantCitation5. This study showed that FH was associated with a >2-fold higher risk of long-term major adverse cardiovascular and cerebrovascular events (HR: 2.30; 95% CI: 1.09–4.84; p = .028)Citation5. Another study investigated outcomes following 1000 percutaneous infrainguinal interventions performed for claudication (46.3%) or limb-threatening ischaemia (53.7%)Citation6. Hypercholesterolaemia was a strong risk factor for reduced primary patency and recurrent interventions (HR: 1.72; 95% CI: 1.24–2.39; p = .001)Citation6. In patients requiring a recurrent intervention, approximately one fifth (20.5%) eventually underwent a major amputation. These findings suggest that PAD patients with FH undergoing an intervention will have low primary patency rates and high primary intervention failure rates, as well as high recurrent intervention and amputation ratesCitation6.
In conclusion, besides the association between FH and non-coronary atherosclerotic cardiovascular diseaseCitation1, vascular surgeons/specialists should bear in mind not only that patients with FH have a high incidence of vascular diseases, but also that the manifestations of these diseases appear in more advanced forms and earlier in life compared with the general populationCitation2–4. Finally, patients with FH undergoing a vascular procedure have higher failure rates and poorer long-term outcomes compared with individuals without FHCitation5,Citation6. Earlier diagnosis and more aggressive treatment of FH patients at all times, including perioperatively, with intensive lipid lowering therapy (e.g. high-dose statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitorsCitation7,Citation8), may prove beneficial. A well designed study comparing very aggressive vs usual treatment is justified.
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References
- Anagnostis P, Vaitsi K, Mintziori G, et al. Non-coronary atherosclerotic cardiovascular disease in patients with familial hypercholesterolaemia. Curr Med Res Opin. 2020;36(5):731–740.
- Liapis CD, Bell PF, Mikhailidis DP, et al. ESVS guidelines: section a – prevention in patients with carotid stenosis. Curr Vasc Pharmacol. 2010;8(5):673–681.
- Naylor AR, Ricco JB, de Borst GJ, et al. Editor’s choice – management of atherosclerotic carotid and vertebral artery disease: 2017 Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS). Eur J Vasc Endovasc Surg. 2018;55:3–81.
- Iyen B, Qureshi N, Kai J, et al. Risk of cardiovascular disease outcomes in primary care subjects with familial hypercholesterolaemia: a cohort study. Atherosclerosis. 2019;287:8–15.
- Wang X, Cai G, Wang Y, et al. Comparison of long-term outcomes of young patients after a coronary event associated with familial hypercholesterolemia. Lipids Health Dis. 2019;18(1):131.
- DeRubertis BG, Faries PL, McKinsey JF, et al. Shifting paradigms in the treatment of lower extremity vascular disease: a report of 1000 percutaneous interventions. Ann Surg. 2007;246(3):415–422.
- Katsiki N, Giannoukas AD, Athyros VG, et al. Lipid-lowering treatment in peripheral artery disease. Curr Opin Pharmacol. 2018;39:19–26.
- Bonaca MP, Nault P, Giugliano RP, et al. Low-density lipoprotein cholesterol lowering with evolocumab and outcomes in patients with peripheral arterial disease: insights from the FOURIER Trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk). Circulation. 2018;137(4):338–350.