Abstract:
Heterozygous familial hypercholesterolemia (HeFH) patients are the prime example of subjects who are at high risk for both acute myocardial infarction (AMI) and ischemic stroke during, and post, SARS-CoV-2 infection. HeFH per se, if left untreated, results in premature clinical atherosclerosis often presenting in the fourth or fifth decade of life. The other concern in HeFH is endothelial dysfunction which is already evident from early childhood. In untreated HeFH patients, the severe hypercholesterolemia causes endothelial dysfunction from an early age, and as a result thereof, atherosclerotic lesions develop prematurely, particularly in the coronary arteries, and result in further endothelial dysfunction and inflammation in these critical segments of the arterial tree. As the pre-existing endothelial dysfunction in HeFH patients is most likely sensitive to further direct and indirect SARS-CoV-2 virus-dependent damage, we can infer that HeFH serves as an example of a comorbidity that predicts a poorer prognosis with COVID-19 infection. Indeed, a large US national database study showed that patients diagnosed with HeFH and SARS-CoV-2 infection had significantly increased Annualized Incidence Density Rates (AIDRs) of AMI when compared to matched HeFH controls not having been diagnosed with SARS-CoV-2 infection. Effective cholesterol lowering is essential for the prevention, or at least alleviation, of the detrimental effects of SARS-CoV-2 infection among HeFH patients. Due to the pre-existing subclinical or even clinical atherosclerotic cardiovascular disease in subjects with HeFH, cholesterol-lowering treatment needs to be continued or, better still, intensified during, and for an extended period post, SARS-CoV-2 infection.
摘要:
杂合子家族性高胆固醇血症(HeFH)患者是在急性心肌梗死(AMI)和缺血性中风期间处于高风险的受试者的主要例子,和帖子,SARS-CoV-2感染。HeFH本身,如果不及时治疗,导致早期临床动脉粥样硬化,通常出现在生命的第四或第五个十年。HeFH的另一个问题是内皮功能障碍,这在儿童早期就已经很明显。在未经治疗的HeFH患者中,严重的高胆固醇血症从早期就引起内皮功能障碍,因此,动脉粥样硬化病变过早发展,特别是在冠状动脉中,并导致动脉树的这些关键段进一步的内皮功能障碍和炎症。由于HeFH患者预先存在的内皮功能障碍很可能对进一步的直接和间接SARS-CoV-2病毒依赖性损伤敏感,我们可以推断,HeFH是预测COVID-19感染预后较差的合并症的一个例子。的确,美国一项大型国家数据库研究显示,与未被诊断为SARS-CoV-2感染的HeFH对照者相比,被诊断为HeFH和SARS-CoV-2感染的患者AMI的年化发病率密度(AIDRs)显著增加.有效降低胆固醇对预防至关重要,或者至少是缓解,SARS-CoV-2感染对HeFH患者的有害影响。由于HeFH受试者预先存在亚临床甚至临床动脉粥样硬化性心血管疾病,需要继续进行降胆固醇治疗,或者,更好的是,期间加剧,对于一个长期的职位,SARS-CoV-2感染。