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).