Evaluation of Clinical Features including the frequency of Familial Hypercholesterolemia, and 2-Year Cardiovascular Outcomes in Patients with Early Acute Coronary Syndrome: Real-Life Data from a Retrospective Cohort

Meral Kayikcioglu, Bahadir Alan, Burcu Yağmur — Thu, 31 Aug 2023 00:00:00 +0000

Objective: This retrospective study, based on real-life data, aimed to evaluate the clinical characteristics and 2-year cardiovascular outcomes in patients presenting with early acute coronary syndrome (ACS) in a tertiary healthcare center.
Methods: Information including at least 2-year endpoint data after index ACS event was retrieved from hospital records. Age limit for early ACS was considered <55 years for males and <60 years for females.
Results: Of 985 consecutive ACS patients (770 males; age range, 21-93 years) 361 (36.6%) met early ACS criteria. Frequency familial hypercholesterolemia (FH) was 7.6% and higher in the young-age group (15.5%) than in the old-age group (3%) (p<0.001). During the follow-up (30 monts), the risk predictors for cardiovascular events were the index event being ST-segment elevation myocardial infarction or non-ST-segment elevation myocardial infarction and the presence of hypertension, and the risk predictors for mortality were female sex, older age, in-hospital cardiovascular complications.
Conclusion: A very high rate of early ACS (36.6%) was observed in this retrospective ACS cohort of a single center from Turkey. Compared to older patients, young patients were more smoking, more obese, less diabetic, and less hypertensive. High total cholesterol, high triglycerides, low HDL-cholesterol levels, high non-HDL cholesterol, family history of CAD, and FH were also more commonly observed in the young group. High FH prevalence might be a major factor of the high prevalence of premature ACS in this population. Both the in-hospital and 2-year follow-up mortality rates were significantly lower in the old-age group.

PCSK9 in extrahepatic tissues: What can we expect from its inhibition?

Angela Pirillo, Lale Tokgözoğlu, Alberico L. Catapano — Thu, 31 Aug 2023 00:00:00 +0000

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme that belongs to the serine protease family and plays a key role in regulating low-density lipoprotein cholesterol (LDL-C) levels in the blood. PCSK9 binds to the LDL receptor (LDLR), targeting it for degradation, resulting in an increase in circulating LDL-C levels. Loss-of-function mutations in the PCSK9 gene are associated with lower LDL-C levels and lower cardiovascular risk; in contrast, gain-of-function mutations are a cause of familial hypercholesterolaemia. The identification of PCSK9 as a pharmacological target led to the development of inhibitors for the treatment of hypercholesterolaemia. To date, the monoclonal antibodies evolocumab and alirocumab (which target plasma PCSK9) and the small-interfering RNA inclisiran (which targets hepatic PCSK9 mRNA) have been approved for the treatment of hypercholesterolaemia. Although hepatic PCSK9 plays a central role in regulating plasma LDL-C levels, this protein is also expressed in other tissues, including the brain, pancreas, heart, kidney, intestine and adipose tissue. In extrahepatic tissues, the functions of PCSK9 are both dependent and independent of LDLR and not necessarily harmful. For this reason, it is essential to uncover any potentially harmful effects of therapies that inhibit PCSK9, beyond their known LDL-C-lowering and CV risk-reducing effects.

European Atherosclerosis Journal

Evaluation of Clinical Features including the frequency of Familial Hypercholesterolemia, and 2-Year Cardiovascular Outcomes in Patients with Early Acute Coronary Syndrome: Real-Life Data from a Retrospective Cohort

PCSK9 in extrahepatic tissues: What can we expect from its inhibition?