Awareness, knowledge and trust in the Greek authorities towards COVID-19 pandemic: results from the Epirus Health Study cohort.

BACKGROUND: To assess the level of knowledge and trust in the policy decisions taken regarding the coronavirus disease (COVID-19) pandemic among Epirus Health Study (EHS) participants. METHODS: The EHS is an ongoing and deeply-phenotyped prospective cohort study that has recruited 667 participants in northwest Greece until August 31st, 2020. Level of knowledge on coronavirus (SARS-CoV-2) transmission and COVID-19 severity was labeled as poor, moderate or good. Variables assessing knowledge and beliefs towards the pandemic were summarized overall and by sex, age group (25-39, 40-49, 50-59, ≥60 years) and period of report (before the lifting of lockdown measures in Greece: March 30th to May 3rd, and two post-lockdown time periods: May 4th to June 31st, July 1st to August 31st). A hypothesis generating exposure-wide association analysis was conducted to evaluate the associations between 153 agnostically-selected explanatory variables and participants' knowledge. Correction for multiple comparisons was applied using a false discovery rate (FDR) threshold of 5%. RESULTS: A total of 563 participants (49 years mean age; 60% women) had available information on the standard EHS questionnaire, the clinical and biochemical measurements, and the COVID-19-related questionnaire. Percentages of poor, moderate and good knowledge status regarding COVID-19 were 4.5, 10.0 and 85.6%, respectively. The majority of participants showed absolute or moderate trust in the Greek health authorities for the management of the epidemic (90.1%), as well as in the Greek Government (84.7%) and the official national sources of information (87.4%). Trust in the authorities was weaker in younger participants and those who joined the study after the lifting of lockdown measures (p-value≤0.001). None of the factors examined was associated with participants' level of knowledge after correction for multiple testing. CONCLUSIONS: High level of knowledge about the COVID-19 pandemic and trust in the Greek authorities was observed, possibly due to the plethora of good quality publicly available information and the timely management of the pandemic at its early stages in Greece. Information campaigns for the COVID-19 pandemic should be encouraged even after the lifting of lockdown measures to increase public awareness.

Role of 9p21 and 2q36 variants and arterial stiffness in the prediction of coronary artery disease.

BACKGROUND: Genetic polymorphisms and arterial stiffness indices have been associated with cardiovascular prognosis and the presence and extent of angiographic coronary artery disease (CAD). We aimed to investigate whether arterial stiffness indices and 9p21 and 2q36 variants may improve prediction of CAD presence and extent when added to classical cardiovascular risk factors in patients at high risk for CAD. MATERIALS AND METHODS: In this cross-sectional study, we enrolled 183 consecutive patients with suspected stable CAD (age 61 ± 9 years, 134 males) referred for diagnostic coronary angiography. Framingham risk score (FRS) was calculated. Arterial stiffness was assessed by carotid-femoral pulse wave velocity (PWV) and central augmentation index (AIx) using applanation tonometry. Genetic polymorphisms of 9p21 (rs1333049) and 2q36 (rs2943634) loci were also analysed. RESULTS: Higher FRS and PWV and the presence of rs2943634 risk allele were independent predictors of CAD (Nagelkerke R(2) 0·252, P < 0·001), while higher FRS and the presence of rs1333049 risk allele were independent predictors of multivessel CAD (Nagelkerke R(2) 0·190, P < 0·001). Genetic polymorphisms and vascular indices did not improve the predictive accuracy of FRS-based models (P > 0·1 for all) for CAD presence or extent. CONCLUSIONS: In these high-risk patients, 9p21 and 2q36 variants and PWV were independently associated with CAD presence and extent, but the addition of both genetic data and arterial stiffness indices to FRS did not improve the prediction of CAD compared with FRS alone. Further studies are needed to clarify the prognostic role of genetic and vascular indices in the prediction of angiographic CAD.

Endothelial dysfunction, but not structural atherosclerosis, is evident early in children with heterozygous familial hypercholesterolemia.

Children with heterozygous familial hypercholesterolemia (heFH) are prone to premature atherosclerosis. Vascular endothelial dysfunction may predict increased cardiovascular risk in children with heFH. The aim of this study was to assess for early functional and structural vascular changes in children with heFH. This cross-sectional study included 30 children with heFH (mean age 12 years) and 30 age- and sex-matched controls. Brachial artery flow-mediated dilation (FMD), carotid intima-media thickness (cIMT), carotid-femoral pulse wave velocity, and large- and small vessel compliance were measured noninvasively. HeFH children exhibited significantly greater total and LDL cholesterol, apolipoprotein B, and lipoprotein (a) levels (p < 0.05 for all) and lower FMD (6.23 ± 3.88 vs. 9.46 ± 4.54 %, p < 0.004) compared with controls. When children were divided in age subgroups, FMD was found to be significantly decreased in heFH compared with control subjects only in ages >10 years (p < 0.05). However, FMD was found to be similarly impaired in heFH children in all age subgroups (two-way analysis of variance, p = 0.39). No differences in other vascular function indices were found. In heFH patients, but not in controls, FMD was inversely correlated with cIMT (r = -0.378, p = 0.036). In conclusion, endothelial dysfunction occurs early in heFH children indicating an increased risk for premature cardiovascular disease and reflecting probably the need for early initiation of anticholesterolemic treatment. Decreased FMD is detected before structural atherosclerotic changes occur.

Adherence to Mediterranean Diet and Cognitive Abilities in the Greek Cohort of Epirus Health Study.

The Mediterranean diet is commonly proposed as a major modifiable protective factor that may delay cognitive impairment in the elderly. The aim of the study was to investigate the cross-sectional association of adherence to the Mediterranean diet with cognitive abilities in a younger Greek population. A total of 1201 healthy adults aged 21-77 years (mean: 47.8) from the Epirus Health Study cohort were included in the analysis. Adherence to the Mediterranean diet was measured using the 14-point Mediterranean Diet Adherence Screener (MEDAS) and cognition was measured using the Trail Making Test, the Verbal Fluency test and the Logical Memory test. Statistical analysis was performed using multiple linear regression models adjusted for age, sex, education, body mass index, smoking status, alcohol consumption and physical activity. Overall, no association was found between the MEDAS score and cognitive tests, which could be explained by the young mean age and high level of education of the participants. Future studies should target young and middle-aged individuals to gain further understanding of the association between Mediterranean diet and cognition in this age group.

Prevalence and Determinants of Sex-Specific Dietary Supplement Use in a Greek Cohort.

We describe the profile of dietary supplement use and its correlates in the Epirus Health Study cohort, which consists of 1237 adults (60.5% women) residing in urban north-west Greece. The association between dietary supplement use and demographic characteristics, lifestyle behaviors, personal medical history and clinical measurements was assessed using logistic regression models, separately for women and men. The overall prevalence of dietary supplement use was 31.4%, and it was higher in women (37.3%) compared to men (22.4%; p-value = 4.2-08). Based on multivariable logistic regression models, dietary supplement use in women was associated with age (positively until middle-age and slightly negatively afterwards), the presence of a chronic health condition (OR = 1.71; 95% CI, 1.18-2.46), lost/removed teeth (OR = 0.52; 95% CI, 0.35-0.78) and diastolic blood pressure (OR per 5 mmHg increase =0.84; 95% CI, 0.73-0.96); body mass index and worse general health status were borderline inversely associated. In men, dietary supplement use was positively associated with being employed (OR = 2.53; 95% CI, 1.21-5.29). A considerable proportion of our sample used dietary supplements, and the associated factors differed between women and men.

The importance of characteristics of angina symptoms for the prediction of coronary artery disease in a cohort of stable patients in the modern era.

OBJECTIVE: Angina is an important clinical symptom indicating underlying coronary artery disease (CAD). Its characteristics are important for the diagnosis and risk stratification of patients with CAD. Currently, we aimed to investigate the association of chest pain characteristics with the presence of obstructive CAD in a contemporary cohort of patients undergoing coronary angiography for suspected stable CAD. METHODS: Consecutive patients undergoing coronary angiography for suspected stable CAD (n = 686) in a single university hospital cardiology department were enrolled. Chest pain was classified as typical angina, atypical angina, nonangina chest pain, and lack of symptoms. The presence of significant angiographic CAD was diagnosed by standard coronary angiography. RESULTS: Typical angina symptoms were associated with a higher prevalence of CAD (odds ratio [OR], 3.47, p < 0.001), whereas atypical angina symptoms were associated with a lower prevalence of CAD (OR, 0.49, p = 0.003) than the nonangina symptoms/or asymptomatic status. In multivariate analysis, typical angina symptoms remained an independent predictor of CAD (OR, 2.54, p < 0.001), with a greater predictive accuracy than other clinical risk factors (area under the curve [AUC], 0.715, p < 0.001) and similar to the accuracy of the high-sensitivity C-reactive protein (AUC, 0.712, p < 0.001). In a multivariate model, the combination of all studied factors further improved the predictive accuracy (AUC, 0.81, p < 0.001). CONCLUSION: In a contemporary cohort of patients referred for coronary angiography for stable CAD, the presence of typical angina symptoms was the most important independent predictor of obstructive CAD. The association of atypical angina symptoms with low CAD prevalence compared to nonangina chest pain or absence of significant symptoms probably reflects different management and referral strategies in these groups of patients.

Distinct association of SLC19A1 polymorphism -43T>C with red cell folate levels and of MTHFR polymorphism 677C>T with plasma folate levels.

OBJECTIVES: The role of SLC19A1 -43T>C, MTHFR 677C>T and MS 2756A>G polymorphisms on red cell and plasma folate levels. DESIGN AND METHODS: Genotype analysis of the three polymorphisms. Red cell and plasma folate measurements in 64 patients with coronary artery disease. RESULTS: The non-wild type allele of SLC19A1 polymorphism -43T>C was associated with low red cell folate levels and the non-wild type allele of MTHFR polymorphism 677C>T with low plasma folate levels. CONCLUSION: SLC19A1 and MTHFR genes are differently associated with red cell and plasma folate levels.

Interleukin-1 genotypes modulate the long-term effect of lipoprotein(a) on cardiovascular events: The Ioannina Study.

BACKGROUND: Lipoprotein(a) [Lp(a)] is a genetic risk factor for cardiovascular disease (CVD), and proinflammatory interleukin-1 (IL-1) genotypes may influence Lp(a)-mediated CVD events. The genotype IL-1(+) is associated with higher rates of inflammation than IL-1(-) genotype. Targeting IL-1ß was recently shown to decrease CVD events independent of low-density lipoprotein-cholesterol levels. OBJECTIVE: The objective of the study is to assess the modulatory effect of IL-1 genotypes on risk mediated by Lp(a) METHODS: We assessed whether IL-1 genotypes modulate the effect of Lp(a) on major adverse cardiovascular events (cardiovascular death, myocardial infarction, and stroke/transient ischemic attack) and angiographically determined coronary artery disease (CAD). IL-1 genotypes and Lp(a) were measured in 603 patients without diabetes mellitus undergoing angiography. Major adverse cardiovascular events and CAD were assessed over a median of 45 months. RESULTS: In multivariable-adjusted analysis, Lp(a) was associated with major adverse cardiovascular events (hazard ratio [HR] [95% confidence interval {CI}]: 2.95 [1.16-7.54], P = .023) and CAD (odds ratio [OR] [95% CI]: 1.84 [1.12-3.03], P = .016) comparing quartile 4 vs quartile 1. In Cox regression analysis, IL-1(+) patients with Lp(a) above the median (>9.2 mg/dL) had a worse event-free cumulative survival (HR [95% CI]: 3.59 [1.07-12.03], P = .039) compared to IL-1(-) patients with Lp(a) below the median. In IL-1(+) patients aged ≤60 years, Lp(a) was also associated with angiographically determined CAD (OR [95% CI]: 2.90 [1.07-7.86], P = .036) comparing quartile 4 vs quartile 1 but not IL-1(-) patients. CONCLUSION: Proinflammatory IL-1(+) genotypes modulate the risk of Lp(a) long-term CVD events and CAD. These data suggest that the dual genetic contributions of elevated Lp(a) levels and IL-1(+) genotypes may identify younger subjects at particularly high risk for CVD events.

Impact of renin-angiotensin-aldosterone system genes on the treatment response of patients with hypertension and metabolic syndrome.

OBJECTIVE: To evaluate the influence of clinical, biochemical and genetic markers on the response to antihypertensive treatment in patients with essential hypertension and the metabolic syndrome (MetS). METHODS: Measurements of anthropometric indices, blood pressure (BP), and metabolic parameters were obtained from the medical records of 132 (77 women) newly diagnosed, untreated hypertensive patients. Renin-angiotensin-aldosterone system (RAAS) genes polymorphisms (including ACE I/D, angiotensinogen M235T, angiotensin II type 1 receptor [AT1-receptor] A1166C) were determined. Response to treatment was defined as BP less than 140/90 mmHg. RESULTS: Patients with MetS (n=60) had higher systolic BP and pulse pressure and a more atherogenic lipid profile than patients without MetS. The frequencies of the ACE and the AT1-receptor gene polymorphisms were similar between patients with and without MetS. Response to treatment was positively associated with pulse pressure, and the presence of the C allele as well as the AC genotype of the AT1-receptor gene and inversely with age after adjustment for confounding factors. CONCLUSIONS: RAAS genes distribution does not differ between hypertensive patients with and without the MetS. Higher baseline pulse pressure levels, the presence of the C allele and/or the AC genotype may be in favour of a better response to structured antihypertensive treatment in patients with MetS. However, these findings need to be evaluated in future studies.

Extent of coronary artery disease in patients undergoing angiography for stable or acute coronary syndromes.

BACKGROUND: We aimed to investigate whether the angiographic extent of coronary artery disease (CAD) differs in patients undergoing coronary angiography for stable CAD or acute coronary syndrome (ACS) and identify predictors of CAD extent in these patients. METHODS: We enrolled 584 consecutive patients (463 with stable CAD, 121 with ACS) with angiographically established CAD (≥1 stenosis >25%). The Gensini score was used to assess the extent of coronary atherosclerosis. RESULTS: Stable CAD patients had greater Framingham risk score and greater prevalence of hypertension, hypercholesterolemia, and diabetes (p<0.05 for all). Fasting glucose and systolic and diastolic blood pressure were higher, while high-sensitivity C-reactive protein (hsCRP) levels were lower in patients with stable CAD than in those with ACS (p<0.05 for all). No difference in Gensini score was observed between the two groups (p=0.118), but patients with ACS were more likely to have at least one significant epicardial angiographic lesion (>50% stenosis) (OR 2.0, p=0.022). Higher Gensini score was independently associated with (i) higher hsCRP and glucose levels, hypercholesterolemia, and increased age in stable CAD patients (R2 0.15, p<0001) and (ii) increased age and higher glucose and hsCRP levels in patients with ACS (R2 0.17, p<0001). CONCLUSIONS: Patients undergoing coronary angiography for ACS or stable CAD presented with a similar extent of angiographic CAD, although patients with ACS had a higher prevalence of significant lesions in the presence of a better cardiovascular risk profile and higher inflammation levels. The extent of angiographic CAD in both the groups shared common determinants such as hsCRP, age, and hyperglycemia, but these appeared to explain only a small part of the variation of coronary atherosclerosis.

Increased aortic pulse wave velocity is associated with the presence of angiographic coronary artery disease in overweight and obese patients.

BACKGROUND: Increased arterial stiffness assessed by carotid-femoral pulse wave velocity (CFPWV) and central augmentation index (AIx), has been associated with a worse cardiovascular prognosis and increased prevalence of angiographic coronary artery disease (CAD). Obesity, a well-recognized cardiovascular risk factor, has been related to increased arterial stiffness, although not consistently. The aim of this work was to investigate the association of arterial stiffness indices with obesity measures in patients undergoing coronary angiography and to study any potential association of arterial stiffness with angiographic CAD in relation to obesity. METHODS: Three hundred ninety-three patients with suspected stable CAD (aged 61±10 years; n = 303 men) referred for diagnostic coronary angiography were included. Body mass index (BMI), waist circumference (WC), and traditional cardiovascular risk factors were measured. Arterial stiffness was assessed by CFPWV and AIx using applanation tonometry in all patients. RESULTS: CFPWV was not associated with obesity measures in multiple-adjusted logistic regression analysis (P > 0.05), whereas AIx was inversely associated with BMI and WC (P < 0.05 for both). Increased CFPWV was associated with CAD in overweight and obese patients (BMI ≥25kg/m(2); WC ≥94cm in men and ≥80cm in women; P < 0.05). No association of AIx with CAD was found (P > 0.05). CONCLUSIONS: Arterial stiffness indices were not consistently associated with obesity, opposite to what might have been expected. The association of increased CFPWV with the presence of angiographic CAD in patients with increased BMI or WC values warrants further research.

Paradoxical protective effect of central obesity in patients with suspected stable coronary artery disease.

OBJECTIVE: Increased body mass index (BMI) has been paradoxically inversely associated with the presence of angiographic coronary artery disease (CAD). Central obesity measures, considered to be more appropriate for assessing obesity-related cardiovascular risk, have been little studied in relation to the presence of CAD. The aim was to investigate the association of central obesity with the presence of angiographic CAD as well as the prognostic significance of obesity measures in CAD prediction when added to other cardiovascular risk factors. DESIGN AND METHODS: Patients with suspected stable CAD (n = 403, age 61 ± 10 years, 302 males) referred for diagnostic coronary angiography with documented anthropometric data were enrolled. RESULTS: Significant angiographic CAD was found in 51% of patients. Both BMI (OR = 0.64 per 1 SD increase, P = 0.001) and waist circumference (WC) (OR = 0.54 per 1 SD increase, P < 0.001) were inversely associated with the presence of CAD even after adjustment for cardiovascular risk factors. In subgroup analysis, BMI and WC were significantly inversely associated with the presence of CAD in males, non diabetics, patients >60 years old and patients with Framingham risk score (FRS) >20% (P < 0.01 for all). The addition of BMI or WC in FRS-based regression models improved prediction of CAD (P = 0.03 and P < 0.001 for BMI and WC respectively) without a significant difference between the two models (P = 0.08). CONCLUSIONS: Central and overall obesity were independently associated with a reduced prevalence of angiographic CAD, lending further credence to the existence of the 'obesity paradox'. Obesity measures may further improve risk discrimination for the presence of CAD when added in an established risk score such as FRS.

Short-term hormone therapy improves sCD40L and endothelial function in early menopausal women: potential role of estrogen receptor polymorphisms.

OBJECTIVE: Hormone therapy (HT) has been suggested to improve vascular function and inflammation in menopausal women, although not consistently. We aimed to investigate the effects of HT on endothelial function and inflammation, especially sCD40L, in early menopausal women, and the effect of common estrogen receptor (ER) polymorphisms on vascular responses to HT. STUDY DESIGN: Eighty-four early menopausal women (<3 years in menopause) with menopausal complaints eligible for HT. Forty women received transdermal 17ß-estradiol plus cyclical micronized progesterone for 3 months while 44 did not (controls). MAIN OUTCOME MEASURES: Brachial artery flow-mediated dilation (FMD) and vascular inflammation markers (sICAM, sP-Selectin and sCD40L). Genetic polymorphisms of ERα (PvuII 454-397T>C and XbaI 454-351A>G) and ERß (AluI 1730A>G) were also assessed. RESULTS: The two groups did not differ at baseline. Following HT, vasomotor complaints' severity, blood pressure, LDL, sCD40L, sICAM and sP-Selectin decreased and FMD increased compared to controls (P<0.05 for all). ERß AluI A allele presence was the most important independent predictor of HT-induced increase in FMD while ERα XbaI A allele was the only independent predictor of decrease in sCD40L. CONCLUSIONS: Short-term HT in early menopausal women improved endothelial function and inflammation. Specific ER polymorphisms that were found to be main determinants of HT-induced effects on endothelium could identify subgroups of women who may benefit the most from HT.

Changes in vascular function and structure in juvenile idiopathic arthritis.

OBJECTIVE: Chronic inflammatory diseases in adults have been associated with increased cardiovascular risk and impaired vascular function. We aimed to assess the presence of early vascular dysfunction in patients with juvenile idiopathic arthritis (JIA) and investigate the role of inherent inflammatory process of JIA in vascular health. METHODS: Thirty patients with JIA (age range 7-18 years) were compared to 33 age- and sex-matched controls. Endothelial function (brachial artery flow-mediated dilation [FMD]), carotid intima-media thickness (IMT), and arterial stiffness were examined. Endothelial inflammation was assessed by intercellular adhesion molecule 1 (ICAM-1) and P-selectin measurements. RESULTS: Patients with JIA showed decreased FMD compared to controls (P = 0.001), independent of age (P = 0.9 among age subgroups). Baseline differences in erythrocyte sedimentation rate, ICAM-1, and glucose between the 2 groups accounted for the difference in FMD. The presence of systemic JIA was associated with greater IMT compared to patients with oligoarticular disease, polyarticular disease, or controls (P = 0.014, P = 0.069, and P = 0.046, respectively). The difference in IMT between systemic versus oligoarticular/polyarticular JIA was attributed to the following risk factors: age, body mass index, blood pressure, disease activity, and corticosteroids use. There were no differences in arterial stiffness indices between JIA patients and controls or between patients with systemic versus nonsystemic disease. CONCLUSION: Endothelial function is impaired in patients with JIA at a very young age, while IMT is increased only in the presence of systemic JIA. Vascular dysfunction may be partly attributed to the effects of disease-related characteristics (inflammation, disease activity, and medications).

Automated diagnosis of coronary artery disease based on data mining and fuzzy modeling.

A fuzzy rule-based decision support system (DSS) is presented for the diagnosis of coronary artery disease (CAD). The system is automatically generated from an initial annotated dataset, using a four stage methodology: 1) induction of a decision tree from the data; 2) extraction of a set of rules from the decision tree, in disjunctive normal form and formulation of a crisp model; 3) transformation of the crisp set of rules into a fuzzy model; and 4) optimization of the parameters of the fuzzy model. The dataset used for the DSS generation and evaluation consists of 199 subjects, each one characterized by 19 features, including demographic and history data, as well as laboratory examinations. Tenfold cross validation is employed, and the average sensitivity and specificity obtained is 62% and 54%, respectively, using the set of rules extracted from the decision tree (first and second stages), while the average sensitivity and specificity increase to 80% and 65%, respectively, when the fuzzification and optimization stages are used. The system offers several advantages since it is automatically generated, it provides CAD diagnosis based on easily and noninvasively acquired features, and is able to provide interpretation for the decisions made.