Mediterranean diet trajectories and 20-year incidence of cardiovascular disease: The ATTICA cohort study (2002-2022).

BACKGROUND AND AIMS: Only few studies have assessed longitudinal dietary trends in relation to cardiovascular disease (CVD) risk. We aimed to evaluate the association between adherence to the Mediterranean diet, both baseline and longitudinal, and 20-year CVD incidence. METHODS AND RESULTS: This was a prospective study among 1988 Greek adults (50% men, age: 45 ± 14years). Adherence to the Mediterranean diet was evaluated at baseline and 10 years through the MedDietScore, based on which longitudinal Mediterranean diet trajectories were identified. CVD incidence was recorded at 20 years. Each one-unit increase in baseline MedDietScore was associated with an 8% reduction in 20-year CVD incidence. Compared to subjects in the lowest tertile of baseline MedDietScore, those in the highest exhibited a 44% lower 20-year CVD risk (relative risk: 0.56, 95% confidence interval: 0.32, 0.97) adjusted for age, sex, baseline body mass index, smoking, physical activity, presence of hypercholesterolemia, hypertension and diabetes mellitus, and family history of CVD; further adjustment for high-sensitivity C-reactive protein, uric acid and estimated glomerular filtration rate attenuated this association. Results were similar in models adjusted for longitudinal changes in body weight, physical activity and smoking, and 10-year medical status. Mediterranean diet trajectory analysis revealed that 24.7%, 8.6%, 45.8% and 20.9% of participants longitudinally sustained a low adherence, moved closer, moved away or sustained a high adherence, respectively; among those, the corresponding CVD incidence was 63.3%, 65.5%, 28.1% and 9.4% (p-value<0.001). CONCLUSION: The Mediterranean diet offers long-term protection against CVD, part of which is mediated by inflammation, uricemia and renal function.

Food Compass Score predicts incident cardiovascular disease: The ATTICA cohort study (2002-2022).

BACKGROUND: The Food Compass Score (FCS) is a novel nutrient profiling system, which evaluates food and diet quality. The present study aimed to prospectively assess the relationship of FCS with short-term (10 years) and long-term (20 years) cardiovascular disease (CVD) incidence and to explore whether this relationship is modified by long-term adherence to a Mediterranean type diet (MTD). METHODS: Volunteers of the ATTICA cohort study, with complete data for the calculation of FCS and incident CVD were included (n = 759). Development of CVD was determined at 10 and 20 years after baseline. Dietary intake was assessed through a validated food frequency questionnaire. The FCS was calculated for each participant based on the published algorithm. Long-term adherence to a MTD was evaluated through MedDietScore. RESULTS: FCS was inversely associated with CVD incidence (hazard ratio [HR] for 20-year follow-up = 0.97, 95% confidence interval [CI] = 0.95-0.99; HR for 10-year follow-up = 0.98, 95% CI = 0.96-1.01) in the total sample, as well as in those with a high baseline adherence to a MTD (HR for 20-year follow-up = 0.96, 95% CI = 0.93-0.99; HR for 10-year follow-up = 0.98, 95% CI = 0.95-1.02). FCS was also inversely associated with CVD risk in those who went away from the MTD (HR = 0.97, 95% CI = 0.96-0.99). CONCLUSIONS: FCS, a novel tool for assessing overall diet quality, was also found to be useful in identifying potential CVD candidates in a long-term period, even in populations with good background dietary habits, such as those following a MTD.

Apolipoprotein B, Residual Cardiovascular Risk After Acute Coronary Syndrome, and Effects of Alirocumab.

BACKGROUND: Apolipoprotein B (apoB) provides an integrated measure of atherogenic risk. Whether apoB levels and apoB lowering hold incremental predictive information on residual risk after acute coronary syndrome beyond that provided by low-density lipoprotein cholesterol is uncertain. METHODS: The ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) compared the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome and elevated atherogenic lipoproteins despite optimized statin therapy. Primary outcome was major adverse cardiovascular events (MACE; coronary heart disease death, nonfatal myocardial infarction, fatal/nonfatal ischemic stroke, hospitalization for unstable angina). Associations between baseline apoB or apoB at 4 months and MACE were assessed in adjusted Cox proportional hazards and propensity score-matched models. RESULTS: Median follow-up was 2.8 years. In proportional hazards analysis in the placebo group, MACE incidence increased across increasing baseline apoB strata (3.2 [95% CI, 2.9-3.6], 4.0 [95% CI, 3.6-4.5], and 5.5 [95% CI, 5.0-6.1] events per 100 patient-years in strata <75, 75-<90, ≥90 mg/dL, respectively; Ptrend<0.0001) and after adjustment for low-density lipoprotein cholesterol (Ptrend=0.035). Higher baseline apoB stratum was associated with greater relative (Ptrend<0.0001) and absolute reduction in MACE with alirocumab versus placebo. In the alirocumab group, the incidence of MACE after month 4 decreased monotonically across decreasing achieved apoB strata (4.26 [95% CI, 3.78-4.79], 3.09 [95% CI, 2.69-3.54], and 2.41 [95% CI, 2.11-2.76] events per 100 patient-years in strata ≥50, >35-<50, and ≤35 mg/dL, respectively). Compared with propensity score-matched patients from the placebo group, treatment hazard ratios for alirocumab also decreased monotonically across achieved apoB strata. Achieved apoB was predictive of MACE after adjustment for achieved low-density lipoprotein cholesterol or non-high-density lipoprotein cholesterol but not vice versa. CONCLUSIONS: In patients with recent acute coronary syndrome and elevated atherogenic lipoproteins, MACE increased across baseline apoB strata. Alirocumab reduced MACE across all strata of baseline apoB, with larger absolute reductions in patients with higher baseline levels. Lower achieved apoB was associated with lower risk of MACE, even after accounting for achieved low-density lipoprotein cholesterol or non-high-density lipoprotein cholesterol, indicating that apoB provides incremental information. Achievement of apoB levels as low as ≤35 mg/dL may reduce lipoprotein-attributable residual risk after acute coronary syndrome. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01663402.

Oxidized phospholipids and lipoprotein(a): An update.

Over the past few years, there has been an undiminished interest in lipoprotein(a) [Lp(a)] and oxidized phospholipids (OxPLs), mainly carried on this lipoprotein. Elevated Lp(a) has been established as an independent causal risk factor for cardiovascular disease. OxPLs play an important role in atherosclerosis. The main questions that remain to be answered, however, is to what extent OxPLs contribute to the atherogenicity of Lp(a), what effect hypolipidaemic medications may have on their levels and the potential clinical benefit of their reduction. This narrative review aimed to summarize currently available data on OxPLs and cardiovascular risk, as well as the effect of established and emerging hypolipidaemic medications on Lp(a)-OxPLs.

Assessing forgetfulness and polypharmacy and their impact on health-related quality of life among patients with hypertension and dyslipidemia in Greece during the COVID-19 pandemic.

PURPOSE: We estimate the association between forgetfulness to take medications as prescribed and polypharmacy and health-related quality of life (HRQoL) among a cohort of patients with hypertension, dyslipidemia or both in Greece during the COVID-19 pandemic. METHODS: A telephone survey of 1018 randomly selected adults was conducted in Greece in June 2020. Participants were included in the survey, if they (a) had a diagnosis of hypertension, dyslipidemia or both and (b) were on prescription treatment for these conditions. HRQoL was calculated using the short form (SF) -12 Patient Questionnaire. A multivariable generalized linear regression model (GLM) was used to estimate the association between forgetfulness and polypharmacy and HRQoL, controlling for sociodemographic and health-related covariates. RESULTS: Overall, 351 respondents met the inclusion criteria, of whom 28 did not fully complete the questionnaire (response rate: 92%, n = 323). Of those, 37% were diagnosed with hypertension only, 28% with dyslipidemia only, and 35% with both. Most reported good to average physical (64.1%) and mental health (48.6%). Overall, 25% indicated that they sometimes forget to take their prescribed medications, and 12% took two or more pills multiple times daily. Total HRQoL score was 68.9% (s.d. = 18.0%). About 10% of participants reported paying less attention to their healthcare condition during the pandemic. Estimates of multivariable analyses indicated a negative association between forgetfulness (- 9%, adjusted ß: - 0.047, 95% confidence interval - 0.089 to - 0.005, p = 0.029), taking two or more pills multiple times daily compared to one pill once a day (- 16%, adjusted ß: - 0.068, 95% confidence interval - 0.129 to - 0.008, p = 0.028) and total HRQoL. CONCLUSION: Our results suggest that among adult patients with hypertension, dyslipidemia or both in Greece, those who forget to take their medications and those with more complex treatment regimens had lower HRQoL. Such patients merit special attention and require targeted approaches by healthcare providers to improve treatment compliance and health outcomes.

Anakinra in hospitalized non-intubated patients with coronavirus disease 2019: a Systematic review and meta-analysis.

OBJECTIVES: Acute respiratory distress syndrome and cytokine release syndrome are the major complications of coronavirus disease 2019 (COVID-19) associated with increased mortality risk. We performed a meta-analysis to assess the efficacy and safety of anakinra in adult hospitalized non-intubated patients with COVID-19. METHODS: Relevant trials were identified by searching literature until 24 April 2021 using the following terms: anakinra, IL-1, coronavirus, COVID-19, SARS-CoV-2. Trials evaluating the effect of anakinra on the need for invasive mechanical ventilation and mortality in hospitalized non-intubated patients with COVID-19 were included. RESULTS: Nine studies (n = 1119) were eligible for inclusion in the present meta-analysis. Their bias risk with reference to the assessed parameters was high. In pooled analyses, anakinra reduced the need for invasive mechanical ventilation (odds ratio (OR): 0.38, 95% CI: 0.17-0.85, P = 0.02, I2 = 67%; six studies, n = 587) and mortality risk (OR: 0.32, 95% CI: 0.23-0.45, P < 0.00001, I2 = 0%; nine studies, n = 1119) compared with standard of care therapy. There were no differences regarding the risk of adverse events, including liver dysfunction (OR: 0.75, 95% CI: 0.48-1.16, P > 0.05, I2 = 28%; five studies, n = 591) and bacteraemia (OR: 1.07, 95% CI: 0.42-2.73, P > 0.05, I2 = 71%; six studies, n = 727). CONCLUSIONS: Available evidence shows that treatment with anakinra reduces both the need for invasive mechanical ventilation and mortality risk of hospitalized non-intubated patients with COVID-19 without increasing the risk of adverse events. Confirmation of efficacy and safety requires randomized placebo-controlled trials.

Could Dapagliflozin Attenuate COVID-19 Progression in High-Risk Patients With or Without Diabetes? Behind DARE-19 Concept.

ABSTRACT: 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, 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.

Sodium-Glucose Cotransporter-2 Inhibitors and Protection Against stroke in Patients with type 2 Diabetes and Impaired Renal Function: A Systematic Review and Meta-Analysis.

BACKGROUND: Recent evidence indicates that treatment with sodium-glucose cotransporter-2 inhibitors (SGLT2i) may favorably affect the risk of stroke in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease. OBJECTIVES: This meta-analysis considered data from cardiovascular outcome trials (CVOTs) regarding the effect of SGLT2i treatment on stroke risk in T2DM patients with an emphasis on patients with impaired renal function. SELECTION CRITERIA: Double-blind randomized trials (RCTs) representing CVOTs were included if they compared SGLT2i add-on therapy with placebo, and reported stroke among primary or secondary endpoints. RESULTS: Six eligible multicenter RCTs were included. The pooled analysis of 5 RCTs (n = 40,393) showed a neutral effect on the risk of total stroke from treatment with SGLT2i vs. placebo (hazard ratio, HR 0.90, 95% CI: 0.74-1.09, p = 0.29, I2 = 58%). Subgroup analysis (4 RCTs) involving patients with impaired renal function (n = 17,072) demonstrated a significant benefit in favor of SGLT2i (HR: 0.66, 95% CI: 0.54-0.82, p<0.0001, I2 = 8%). The pooled analysis of 2 RCTs (n = 14,543) showed a significant reduction in the risk of hemorrhagic stroke in T2DM patients (HR: 0.46, 95% CI: 0.25-0.83, p = 0.01; I2 = 0). No differences were noticed regarding the risk of ischemic stroke (HR: 0.97, 95% CI: 0.85-1.12, p = 0.69; I2 = 0), non-fatal stroke (HR: 0.98, 95% CI: 0.83-1.16, p = 0.79, I2 = 28%), and fatal stroke (HR: 0.77, 95% CI: 0.50-1.17, p = 0.22, I2 = 0). CONCLUSIONS: Available data suggest that SGLT2i reduce the risk of total stroke in patients with T2DM and impaired renal function. Based on the findings of two RCTs, these drugs may offer a protection against hemorrhagic stroke.

Achieving low-density lipoprotein cholesterol targets as assessed by different methods in patients with familial hypercholesterolemia: an analysis from the HELLAS-FH registry.

BACKGROUND: Familial hypercholesterolemia (FH) is characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels and increased cardiovascular disease (CVD) risk. FH patients often have increased lipoprotein(a) [Lp(a)] levels, which further increase CVD risk. Novel methods for accurately calculating LDL-C have been proposed. METHODS: Patients with FH were recruited by a network of Greek sites participating in the HELLAS-FH registry. LDL-C levels were calculated using the Friedewald (LDL-CF) and the Martin/Hopkins (LDL-CM/H) equations as well as after correcting LDL-CM/H for Lp(a) levels [LDL-CLp(a)corM/H]. The objective was to compare LDL-C levels and target achievement as estimated by different methods in FH patients. RESULTS: This analysis included 1620 patients (1423 adults and 197 children). In adults at diagnosis, LDL-CF and LDL-CM/H levels were similar [235 ± 70 mg/dL (6.1 ± 1.8 mmol/L) vs 235 ± 69 mg/dL (6.1 ± 1.8 mmol/L), respectively; P = NS], while LDL-CLp(a)corM/H levels were non-significantly lower than LDL-CF [211 ± 61 mg/dL (5.5 ± 1.6 mmol/L); P = 0.432]. In treated adults (n = 966) both LDL-CF [150 ± 71 mg/dL (3.9 ± 1.8 mmol/L)] and LDL-CM/H levels [151 ± 70 mg/dL (6.1 ± 1.8 mmol/L); P = 0.746] were similar, whereas LDL-CLp(a)corM/H levels were significantly lower than LDL-CF [121 ± 62 mg/dL (3.1 ± 1.6 mmol/L); P < 0.001]. Target achievement as per latest guidelines in treated patients using the LDL-CM/H (2.5%) and especially LDL-CLp(a)corM/H methods (10.7%) were significantly different than LDL-CF (2.9%; P < 0.001). In children, all 3 formulas resulted in similar LDL-C levels, both at diagnosis and in treated patients. However, target achievement by LDL-CF was lower compared with LDL-CM/H and LDL-CLp(a)corM/H methods (22.1 vs 24.8 vs 33.3%; P < 0.001 for both comparisons). CONCLUSION: LDL-CLp(a)corM/H results in significantly lower values and higher target achievement rate in both treated adults and children. If validated in clinical trials, LDL-CLp(a)corM/H may become the method of choice to more accurately estimate 'true' LDL-C levels in FH patients.

Lipid testing in infectious diseases: possible role in diagnosis and prognosis.

INTRODUCTION: Acute infections lead to significant alterations in metabolic regulation including lipids and lipoproteins, which play a central role in the host immune response. In this regard, several studies have investigated the role of lipid levels as a marker of infection severity and prognosis. SCOPE OF REVIEW: We review here the role of lipids in immune response and the potential mechanisms underneath. Moreover, we summarize studies on lipid and lipoprotein alterations in acute bacterial, viral and parasitic infections as well as their diagnostic and prognostic significance. Chronic infections (HIV, HBV, HCV) are also considered. RESULTS: All lipid parameters have been found to be significantly dearranged during acute infection. Common lipid alterations in this setting include a decrease of total cholesterol levels and an increase in the concentration of triglyceride-rich lipoproteins, mainly very low-density lipoproteins. Also, low-density lipoprotein cholesterol, apolipoprotein A1, low-density lipoprotein cholesterol and apolipoprotein-B levels decrease. These lipid alterations may have prognostic and diagnostic role in certain infections. CONCLUSION: Lipid testing may be of help to assess response to treatment in septic patients and those with various acute infections (such as pneumonia, leptospirosis and others). Diagnostically, new onset of altered lipid levels should prompt the clinician to test for underlying infection (such as leishmaniasis).

Visceral leishmaniasis is associated with marked changes in serum lipid profile.

BACKGROUND: Infection is often accompanied by lipid profile alterations. The aim of this study was to evaluate the lipid profile changes in patients with visceral leishmaniasis (VL). MATERIALS AND METHODS: We included 15 patients [10 men, aged 50 (24-82) years old] with VL and 15 age- and sex-matched controls. The parameters estimated at diagnosis and 4 months after VL resolution were total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), apolipoproteins (apo) A-Ι, B, E, C-II, C-III, lipoprotein (a) [Lp(a)], activities of lipoprotein-associated phospholipase A2 (Lp-PLA2), HDL-Lp-PLA2, PON1 (paraoxonase 1) and cholesterol ester transfer protein (CETP), cytokines (interleukins 1ß and 6 and tumour necrosis factor α), as well as LDL subfraction profile. RESULTS: Patients with VL at diagnosis had lower levels of TC, LDL-C, apoΒ and Lp(a), and higher TG and apoE concentrations compared with 4 months after VL resolution. The activities of Lp-PLA2, HDL-Lp-PLA2 and ΡΟΝ1 were reduced at diagnosis compared with post-treatment values. VL patients had decreased levels of both large and sdLDL-C at diagnosis; no effect on mean LDL particle size was observed. Patients with VL at diagnosis had decreased HDL-C and apoA-I concentrations; these increased 4 months after VL resolution, but remained lower compared with controls. The activities of HDL-Lp-PLA2 and PON1 remained lower in patients after VL resolution compared with controls. CONCLUSIONS: Patients with VL exhibit increased TG levels and decreased cholesterol subclasses at diagnosis. HDL-C, apoA-I and associated enzymes remain lower 4 months after VL resolution compared with controls.

L-carnitine for the treatment of acute myocardial infarction.

Although the therapeutic strategies available for treating acute myocardial infarction (AMI) have evolved dramatically in recent decades, coronary artery disease remains the leading cause of death in our society, and the rates of recurrent myocardial infarction and mortality are still unacceptably high. Therefore, exploration of alternative therapeutic strategies for AMI is of utmost importance. One such strategy is to target metabolic pathways via L-carnitine supplementation. L-carnitine is a physiologically essential metabolic cofactor that has been shown to provide a plethora of benefits when administered after AMI. L-carnitine has been shown to lessen infarct size, to reduce ventricular arrhythmias, left ventricular dilation, and heart failure incidence, as well as improve survival. These benefits may, in part, be related to its ability to boost glucose oxidation in ischemic tissues, while moderating increases in fatty acyl-coenzyme A levels that can impair mitochondrial efficiency and promote oxidative stress and inflammation. This article summarizes the evidence pertinent to the therapeutic use of L-carnitine for AMI.

No association between high-density lipoprotein levels and ventricular repolarization indexes in subjects with primary hypercholesterolemia.

OBJECTIVE: Data regarding the effect of lipid parameters on repolarization are sparse. Recent data indicate that reconstituted HDL administration shortens repolarization in cardiomyocytes as well as the corrected QT (QTc) interval in human subjects. We investigated the potential association of high-density lipoprotein cholesterol (HDL-C) levels with conventional and novel electrocardiographic markers of ventricular repolarization in patients with hypercholesterolemia. METHODS: Consecutive subjects with primary hypercholesterolemia were recruited. We recorded clinical and laboratory parameters as well as electrocardiographic indexes. With regard to ventricular repolarization, we calculated the QTc interval, the T peak-to-end (Tpe) interval, and the Tpe/QT ratio. RESULTS: The study population consisted of 440 patients (199 men) with a median age of 56 [48-65] years. The correlation analysis (Spearman's) failed to show any association between HDL-C and any of the studied electrocardiographic parameter. Moreover, no correlation between other lipid parameters and the electrocardiograhic indexes was evident. Also, a comparison of the ventricular repolarization parameters between different HDL-C quartile groups (HDL-Q1: ≤ 1.11 mmol/L; HDL-Q2: 1.12-1.29 mmol/L; HDL-Q3: 1.30-1.53 mmol/L; HDL-Q4: ≥ 1.54 mmol/L) was performed. Specifically, the differences in QTc (p: 0.372), Tpe in leads II (p: 0.356), V2 (p: 0.372), V5 (p: 0.112), and Tpe/QT in leads II (p: 0.348), V2 (p: 0.162), V5 (p: 0.122) were not significant. CONCLUSION: HDL-C levels are not associated with the QTc interval or indexes of repolarization dispersion in patients with primary hypercholesterolemia. The potential antiarrhythmic efficacy of HDL should be further evaluated in the setting of myocardial ischemia where dynamic changes in the heterogeneity of ventricular repolarization ensue.

Diabetic Sensorimotor Polyneuropathy: An Overview on Epidemiology, Risk Factors, Classification, Diagnosis, and Treatment.

Diabetic distal symmetric sensorimotor polyneuropathy (DSPN) is a common complication of diabetes with devastating consequences. Hyperglycaemia is the major aetiological factor, while emerging data demonstrate that cardiometabolic risk factors also contribute to its development. Diagnosis of DSPN involves interview of medical and neurological history, foot inspection, and sensory and motor function examination with specific tests such as temperature and pinprick perception for small nerve fibers, and vibration and light touch assessments for large nerve fibers. Management includes optimised glycaemic control, treatment of cardiovascular risk factors, and symptomatic treatment aiming at improving life quality. This article provides an overview on epidemiology, risk factors, classification, diagnosis and current treatment of DSPN.

Retrotransposons and Diabetes Mellitus.

Retrotransposons are invasive genetic elements, which replicate by copying and pasting themselves throughout the genome in a process called retrotransposition. The most abundant retrotransposons by number in the human genome are Alu and LINE-1 elements, which comprise approximately 40% of the human genome. The ability of retrotransposons to expand and colonize eukaryotic genomes has rendered them evolutionarily successful and is responsible for creating genetic alterations leading to significant impacts on their hosts. Previous research suggested that hypomethylation of Alu and LINE-1 elements is associated with global hypomethylation and genomic instability in several types of cancer and diseases, such as neurodegenerative diseases, obesity, osteoporosis, and diabetes mellitus (DM). With the advancement of sequencing technologies and computational tools, the study of the retrotransposon's association with physiology and diseases is becoming a hot topic among researchers. Quantifying Alu and LINE-1 methylation is thought to serve as a surrogate measurement of global DNA methylation level. Although Alu and LINE-1 hypomethylation appears to serve as a cellular senescence biomarker promoting genomic instability, there is sparse information available regarding their potential functional and biological significance in DM. This review article summarizes the current knowledge on the involvement of the main epigenetic alterations in the methylation status of Alu and LINE-1 retrotransposons and their potential role as epigenetic markers of global DNA methylation in the pathogenesis of DM.

Effects of Serum Estradiol on Proprotein Convertase Subtilisin/Kexin Type 9 Levels and Lipid Profiles in Women Undergoing In Vitro Fertilization.

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.

Differential Adherence to Free and Single-Pill Combination of Rosuvastatin/Ezetimibe: Findings from a Real-World Analysis in Italy.

INTRODUCTION: Adherence to cardiovascular drug treatment can significantly benefit from a reduced pill burden, but data on this matter derived from real-life settings are currently scanty. This analysis assessed the possible changes in adherence in patients treated with rosuvastatin and ezetimibe (ROS/EZE) as free multi-pill combination who switched to ROS/EZE as single-pill combination in the setting of real clinical practice in Italy. METHODS: A retrospective analysis was conducted on the administrative databases for a catchment area of about seven million health-assisted residents. Adults receiving ROS/EZE as a single-pill combination from January 2010 to June 2020 (followed up to 2021) were identified. The date of the first prescription of single-pill combination of ROS/EZE was considered as the index date. The analysis included the users of ROS/EZE as a free combination during the year before the index date. Baseline demographic and clinical characteristics were collected during the period of data availability prior to the index date. Adherence to therapy was evaluated as proportion of days covered (PDC), namely the percentage of days during which a patient had access to medication, in the 12-month interval preceding or following the index date (PDC < 25% non-adherence; PDC = 25-75% partial adherence; PDC > 75% adherence). RESULTS: A total of 1219 patients (61.1% male, aged 66.2 ± 10.4 years) were included. Cardiovascular comorbidities were found in 83.3% of them, diabetes in 26.4%, and a combination of both in 16.2%. Single-pill combination of ROS/EZE was associated with a higher proportion of adherent patients compared to free-pill combination (75.2% vs 51.8%, p < 0.001). CONCLUSIONS: This real-world analysis suggested that switching from a regimen based on separate pills to one based on a single-pill combination resulted in improved adherence to ROS/EZE therapy.

Lipid-lowering therapy to control low-density lipoprotein (LDL) cholesterol levels is essential for cardiovascular risk prevention. Successful therapy depends on the type of lipid-lowering therapy, i.e., low or high statin intensity and combination of statins with ezetimibe or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and adherence to therapy, i.e., whether the patient actually takes their pills as prescribed. If there are fewer pills to be taken, this can help patients to follow their treatment. Single-pill combinations of two drugs could facilitate adherence and thus the chances of reaching the recommended lipid targets. Here, we analyzed a sample of Italian patients with dyslipidemia to examine whether the switch from a free combination of two separate pills of rosuvastatin and ezetimibe to a single-pill combination of the same drugs could improve adherence to therapy. We found that the proportion of adherent patients increased from about just over half (51.8%) to about three-fourths (75.1%) when switching from two-pill to single-pill combination of rosuvastatin and ezetimibe. These findings suggest that simplifying therapy can help improve patient adherence, which is essential for reaching lipid targets and ultimately for alleviating atherosclerotic cardiovascular disease.

A real-world analysis of adherence, biochemical outcomes, and healthcare costs in patients treated with rosuvastatin/ezetimibe as single-pill combination vs. free combination in Italy.

Aims: To compare medication adherence, lipid goal attainment, and healthcare costs between patients receiving a single-pill combination (SPC) vs. a free combination treatment (FCT) of rosuvastatin/ezetimibe (ROS/EZE) in Italy. Methods and results: Administrative databases of healthcare entities covering ∼7 million individuals were used to identify adults prescribed with ROS/EZE as SPC or FCT between January 2018 and June 2020. Adherence was calculated as the proportion of days covered (PDC) after cohort balancing by propensity score matching. Patients with available LDL cholesterol testing were assessed for the proportion of those who at baseline were above lipid targets recommended by ESC/EAS Guidelines for their cardiovascular risk category and reached the target during follow-up. Among 25 886 patients on SPC and 7309 on FCT, adherent patients were more represented in SPC than FCT cohort (56.8 vs. 44.5%, P < 0.001), and this difference remained significant (P < 0.001) after stratification by cardiovascular risk (very high, high, and other). The proportion of patients reaching LDL cholesterol target at 1 year follow-up was significantly (P < 0.001) higher in SPC vs. FCT cohort: 35.4 vs. 23.8% for very high cardiovascular risk, 46.9 vs. 23.1% for high risk and 71.6 vs. 49.5% for other risk. Total healthcare costs per patient at 1 year follow-up were lower in SPC vs. FCT users (2337€ vs. 1890€, P < 0.001). In both cohorts, costs were mainly driven by drug expenses and hospitalizations. Conclusion: This real-world analysis in dyslipidaemic patients found that treatment with ROS/EZE as SPC resulted in better adherence, higher chances of reaching lipid goals, and cost savings over FCT, in all cardiovascular risk categories.

Neutrophil Extracellular Traps (NETs) and Atherosclerosis: Does Hypolipidemic Treatment Have an Effect?

Neutrophil extracellular traps (NETs) have attracted much attention recently, beyond elemental host immunity, due to their fundamental implication in a variety of pathologic conditions and widespread impactful diseases. Atherosclerotic cardiovascular disease (ASCVD) is one of them, and a major cause of mortality and disability worldwide. Consequently, years of basic and clinical research were dedicated to shedding light on every possible pathophysiologic mechanism that could be used as an effective prevention and treatment tool to ameliorate its burden. This led to the development of complex and prevention protocols and regimens that are now widely used, with lipid-lowering treatment being the current cornerstone; however, this is not adequate to alleviate the residual cardiovascular risk, which remains prominent. Despite the demonstrated pathogenic role of NETs in the progression and complications of ASCVD, little is known about their potential as a therapeutic target and the effects hypolipidemics exert on them.