Georgia Anastasiou

Background and Aim: Serum alkaline phosphatase (ALP) activity has been associated with atherosclerotic cardiovascular disease (ASCVD). We aimed to investigate the association of ALP with ASCVD in patients with dyslipidemia. Methods: We conducted a retrospective cohort study including consecutive adults with dyslipidemia followed-up for ≥3 years (from 1999 to 2022) in the outpatient Lipid Clinic of Ioannina University General Hospital, Greece. The primary endpoint was the association between baseline ALP and incident ASCVD after adjusting for traditional risk factors (i.e., sex, age, hypertension, diabetes, smoking, and dyslipidemia), baseline ASCVD, and lipid-lowering treatment. ALP levels were stratified by tertiles as follows: low: p = 0.001). Subjects in the highest ALP tertile had the highest odds for ASCVD when compared with those in the lowest tertile (OR: 2.35; 95% CI: 1.24–4.41, p = 0.008). Conclusions: The present study indicates an association between ALP and the development of ASCVD in patients with dyslipidemia, which underscores the potential of ALP as a predictive tool or a therapeutic target in the realm of ASCVD prevention within this population.

Background: Familial hypercholesterolemia (FH) carries a high risk of atherosclerotic cardiovascular disease (ASCVD). As the population ages, the age-related influence on clinical characteristics and outcomes becomes increasingly pertinent. This cross-sectional analysis from the HELLAS-FH registry aims to explore potential differences in clinical characteristics, treatment, ASCVD, and goal achievement between those younger and older than 65 years with FH. Results: A total of 2273 adults with heterozygous FH (51.4% males) were studied. Elderly FH patients (n = 349) had a higher prevalence of ASCVD risk factors, such as hypertension (52.1% vs. 20.9%, p < 0.05) and type 2 diabetes (16.9% vs. 6.0%, p < 0.05), compared to younger patients (n = 1924). They also had a higher prevalence of established ASCVD (38.4% vs. 23.1%, p < 0.001), particularly CAD (33.0% vs. 20.2%, p < 0.001), even after adjusting for major ASCVD risk factors. Elderly patients were more frequently and intensively receiving lipid-lowering treatment than younger ones. Although post-treatment LDL-C levels were lower in elderly than younger patients (125 vs. 146 mg/dL, p < 0.05), both groups had similar attainment of the LDL-C target (3.7% vs. 3.0%). Conclusions: Elderly FH patients have a higher prevalence of ASCVD, particularly CAD. Despite more aggressive treatment, the achievement of LDL-C targets remains very poor. These results emphasize the importance of early FH diagnosis and treatment in reducing ASCVD.

Background: The mechanisms underlying the impact of estradiol (E2) on low-density lipoprotein cholesterol (LDL-C) levels are not completely understood, although a role for proprotein convertase subtilisin/kexin type 9 (PCSK9) has been proposed. We aimed to investigate the association between levels of E2, PCSK9, and lipid parameters in premenopausal women undergoing in vitro fertilization (IVF). Methods: Healthy women undergoing IVF in the Department of Obstetrics and Gynecology of the University General Hospital of Ioannina were recruited. Their levels of E2, PCSK9, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), LDL-C, and triglycerides (TGs) were measured 10 days after ovarian depression (E2min) and 7 days after ovarian stimulation (E2max). Results: We included 34 consecutive women of median age 38 (interquartile range 26–46) years who underwent a full IVF cycle. As expected, E2 levels increased by 329.6% from E2min to E2max (108 [47–346] to 464 [241–2471] pg/mL, p < 0.05). During the same time, serum PCSK9 levels decreased by 30.8% (245 ± 80 to 170 ± 64 ng/mL, p < 0.05). TC, LDL-C, and TGs decreased by 0.4%, 3.8%, and 2.2%, respectively, while HDL-C levels increased by 5.3% (all p = NS). Conclusions: The rise in endogenous E2 during an IVF cycle was related with a significant decline in serum PCSK9 levels, but no significant change in plasma lipids during a 7-day period.

Background and Aim: Serum alkaline phosphatase (ALP) activity has been associated with ath-erosclerotic cardiovascular disease (ASCVD). We aimed to investigate the association of ALP with ASCVD in patients with dyslipidemia. Methods: Retrospective cohort study including consecutive adults with dyslipidemia followed-up for ≥3 years (from 1999 to 2022) in the outpatient Lipid Clinic of Ioannina University General Hospital, Greece. The primary endpoint was the association between baseline ALP and incident ASCVD after adjusting for traditional risk factors (i.e. sex, age, hypertension, diabetes, smoking, dyslipidemia), baseline ASCVD and lipid-lowering treatment. ALP levels were stratified by ter-tiles as follows: low:<67 U/L, middle: 67-79 U/L, high: ≥79 U/L. Results: Overall, 1178 subjects were included; 44% were males and their median age was 57 years (range 49-65). During a 6-year median follow-up (interquartile range IQR: 4-9), 78 new ASCVD events (6.6%) occurred. A statistically significant association between baseline ALP levels and incident ASCVD was demonstrated (Odds Ratio, OR: 6.99, 95% Confidence Interval, CI: 2.29-21.03, p=0.001). Subjects in the highest ALP tertile had the highest odds for ASCVD when compared with those in the lowest tertile (OR: 2.35; 95% CI: 1.24-4.41, p=0.008). Conclusions: The present study demonstrated that ALP is associated with ASCVD development in patients with dyslipidemia.

Background: The mechanisms underlying the effect of estradiol (E2) on low-density lipoprotein cholesterol (LDL-C) levels are not completely understood, although a role for proprotein con-vertase subtilisin/kexin type 9 (PCSK9) has been proposed. We aimed to investigate the association between levels of E2, PCSK9 and lipid parameters in premenopausal women undergoing in vitro fertilization (IVF). Methods: Healthy women undergoing IVF in the Department of Obstetrics and Gynecology of the University General Hospital of Ioannina were recruited. Levels of E2, pro-protein convertase subtilisin/kexin type 9 (PCSK9), total cholesterol (TCHOL), high-density lip-oprotein cholesterol (HDL-C), LDL-C, and triglycerides (TGs) were measured 10 days after ovarian depression (E2min) and 7 days after ovarian stimulation (E2max). Results: A total of 34 consecutive healthy women aged 38 (26-46) years old who underwent a full IVF cycle were included. E2 levels increased by 329.6% from E2min to E2max (108 [47-346] to 464 [241-2471] pg/mL, p<0.05). At the same time, serum PCSK9 levels significantly decreased by 30.8% (245 ± 80 to 170 ± 64 ng/mL, p0.05). Conclusions: The increase in endogenous E2 production during an IVF cycle was associated with a significant decrease in serum PCSK9 levels during a 7-day period.

Background: Statins are associated with new-onset type 2 diabetes (T2D), mainly in patients with metabolic syndrome (MetS). The fatty liver index (FLI) is used as a prognostic score for the diagnosis of non-alcoholic fatty liver disease (NAFLD), which is common in patients with MetS. We aimed to investigate the association of FLI with new-onset T2D in patients initiating statin therapy. Methods: A retrospective observational study including 1241 individuals with dyslipidemia and followed up for ≥3 years. Patients with T2D and those receiving lipid-lowering treatment at the baseline visit were excluded. Models with clinical and laboratory parameters were used to assess the association of FLI with incident T2D. Results: Among the 882 eligible subjects, 11% developed T2D during the follow-up (6 years; IQR: 4–10 years). After adjusting for sex, age and MetS parameters, a multivariate analysis revealed that age (HR:1.05; 95%CI: 1.01–1.09, p < 0.05), fasting plasma glucose (HR: 1.09; 95%CI: 1.06–1.13, p < 0.001) and FLI (HR: 1.02; 95%CI: 1.01–1.04, p < 0.01) were independently associated with T2D risk. The subjects with probable NAFLD (FLI ≥ 60) had a three-fold increased T2D risk compared with the subjects with FLI < 60 (HR: 3.14; 95%CI: 1.50–6.59, p = 0.001). A ROC curve analysis showed that FLI had a significant, although poor, predictive value for assessing T2D risk (C-Statistic: 0.67; 95%CI: 0.58–0.77, p = 0.001). Higher FLI values were associated with reduced T2D-free survival (log-rank = 15.46, p < 0.001). Conclusions: FLI is significantly and independently associated with new-onset T2D risk in patients initiating statin therapy.

Familial hypercholesterolemia (FH) and type 2 diabetes mellitus (T2DM) are both associated with a high risk of atherosclerotic cardiovascular disease (ASCVD). Little is known about the prevalence of T2DM and its association with ASCVD risk in FH patients. This was a cross-sectional analysis from the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH) including adults with FH (n = 1719, mean age 51.3 ± 14.6 years). Of FH patients, 7.2% had a diagnosis of T2DM. The prevalence of ASCVD, coronary artery disease (CAD), and stroke was higher among subjects with T2DM compared with those without (55.3% vs. 23.3%, 48.8% vs. 20.7%, 8.3% vs. 2.7%, respectively, p < 0.001). When adjusted for age, systolic blood pressure, smoking, body mass index, hypertension, waist circumference, triglyceride levels, high-density lipoprotein cholesterol levels, and gender, T2DM was significantly associated with prevalent ASCVD [OR 2.0 (95% CI 1.2–3.3), p = 0.004]. FH patients with T2DM were more likely to have undergone coronary revascularization than those without (14.2% vs. 4.5% for coronary artery bypass graft, and 23.9% vs. 11.5% for percutaneous coronary intervention, p < 0.001). T2DM is associated with an increased risk for prevalent ASCVD in subjects with FH. This may have implications for risk stratification and treatment intensity in these patients.

Epidemiological studies indicate that diabetes is the second most common comorbidity in COVID-19 (Coronavirus Disease-2019). Dapagliflozin, a sodium-glucose co-transporter 2 inhibitor (SGLT2i), exerts direct cardioprotective and nephroprotective effects. DARE-19 (Dapagliflozin in Respiratory Failure in Patients With COVID-19), an ongoing clinical trial, is designed to investigate the impact of dapagliflozin on COVID-19 progression. This article discusses the potential favorable impact of dapagliflozin on COVID-19 and its complications.