Lifestyle Trajectories Are Associated with Incidence of Cardiovascular Disease: Highlights from the ATTICA Epidemiological Cohort Study (2002-2022).

The study aimed to assess the trajectories of lifestyle characteristics and their association with 20-year cardiovascular disease (CVD) incidence. In 2002, 3042 Greek adults (aged: 45 (12) years) free of CVD were enrolled. In 2022, the 20-year follow-up was performed on 2169 participants; of those, 1988 had complete data for CVD. The 20-year CVD incidence was 3600 cases/10,000 individuals; the man-to-woman ratio was 1.25, with the peak difference in the 35-45 age group (i.e., 2.1); however, a reversal of the trend was observed in the age-groups 55-65 and 65-75, with a resumption of an almost equal incidence in those >75 years. In multi-adjusted analysis, age, sex, abnormal waist circumference, hypercholesterolemia, hypertension, and diabetes were positively associated with 20-year CVD risk, explaining 56% of the excess CVD risk, whereas an additional 30% was attributed to lifestyle trajectories; being physically active throughout life-course and being close to the Mediterranean diet were protective, while continuous smoking was detrimental against CVD risk. Mediterranean diet adherence protected against CVD development even if not sustained, while quitting smoking or engaging in physical activities during the 20-year observation did not offer any significant protection. A life-course personalized approach that is cost-effective and long-term sustained is needed to prevent CVD burden.

High fish intake rich in n-3 polyunsaturated fatty acids reduces cardiovascular disease incidence in healthy adults: The ATTICA cohort study (2002-2022).

Background: The long-term effects of high fish intake rich in n-3 fatty acids for deterring cardiovascular disease (CVD) and related adverse outcomes in healthy individuals have not been yet elucidated. Purpose: To evaluate the association between total seafood, as well as small fish, intake on 10- and 20-year CVD incidence and mortality in healthy adults. Methods: A prospective cohort study (n = 2,020) was conducted in healthy community dwelling adults in Athens, Greece, selected following age- and sex-based random multistage sampling (mean ± SD age at baseline: 45.2 ± 14.0 years). Seafood (high (>2 servings/week) vs. low (≤2 servings/week) intake), including small fish rich in n-3 fatty acids (high (>1 serving/week) vs. low (≤1 serving/week) intake), consumption was evaluated by semi-quantitative food frequency questionnaire at baseline. The occurrence of non-fatal and/or fatal CVD events (ICD-10) was assessed during 10- and 20-year follow-up periods. Results: Only 32.7% and 9.6% of participants had high seafood and small fish intakes, respectively. Participants with high seafood intake had 27% decreased 10-year CVD risk (adj. HR:0.73; 95% CI:0.55-0.98) and 74% lower attributable mortality (adj. HR:0.26; 95% CI:0.11-0.58). Participants with high seafood intake also sustained a 24% lower 20-year risk of CVD mortality (adj. HR: 0.76; 95% CI: 0.55-0.98). Moreover, participants with high small fish intake had a lower 10-year CVD risk and 76% decreased risk of 10-year CVD mortality (adj. HR:0.24; 95% CI:0.06-0.99), even among normotensive individuals (adj. HR:0.31; 95% CI:0.13-0.73). When analogous analyses focused on 20-year CVD incidence and mortality, similar but not significant associations were observed (all p-values >0.10). Conclusion: High intake of seafood, and particularly small fish rich in n-3 fatty acids, was associated with a lower risk of 10-year fatal and non-fatal CVD. Thus, public health interventions aimed at enhancing small fish consumption may most effectively deter long-term CVD outcomes, particularly among low risk normotensive individuals.

Irrational beliefs, depression and anxiety, in relation to 10-year cardiovascular disease risk: the ATTICA Epidemiological Study.

BACKGROUND AND OBJECTIVES: Various bio-psychosocial mechanisms underlying the link between anxiety, depression and cardiovascular disease risk, remain unknown. We investigated the role of irrational beliefs in conjunction with anxiety and depression in the 10-year cardiovascular disease (CVD) incidence, and the effect of biochemical and socio-behavioral factors. DESIGN: 853[453 men (45 ± 13 years) and 400 women (44 ± 18 years)] from the ATTICA study (2002-2012) and without evidence of CVD were assessed. METHODS: The Irrational Beliefs Inventory (IBI), the Zung Self-Rating-Depression-Scale (ZDRS) and the State-Trait-Anxiety-Inventory (STAI) were used for the assessments. Incidence of CVD was defined according to the International Coding Diseases (ICD)-10 criteria. RESULTS: Participants with high irrational beliefs and anxiety symptoms had a 138% greater risk of developing CVD during the 10-year follow-up (2.38; 95%CI 1.75, 3.23) as compared to those without anxiety. Among others, C-reactive protein, interleukin-6 and total antioxidant capacity were mediators in the tested association. Interaction of irrational beliefs and depression was not associated with the 10-year CVD in all models. CONCLUSIONS: Inflammation and oxidative stress, partially explained the associations between irrational beliefs and anxiety in predicting CVD risk. These findings advance psychological research in the area of primary prevention of mental health and cardiovascular diseases.

Quality of plant-based diets is associated with liver steatosis, which predicts type 2 diabetes incidence ten years later: Results from the ATTICA prospective epidemiological study.

BACKGROUND & AIMS: Plant-based diets have recently risen in popularity due to their proposed health benefits. We evaluated the association of plant-based diet quality with non alcoholic fatty liver (NAFL) prevalence and their interaction on risk for developing type 2 diabetes ten years later. ETHODS: A post-hoc analysis of data collected in the ATTICA study. In 2001-02, 3042 participants from the Attica region of Greece were recruited. NAFL was assessed through hepatic steatosis index (HSI). Overall, healthful (hPDI), and unhealthful (uPDI) plant-based dietary indices (PDI) were calculated through standard procedures. N = 1485 participants free of type 2 diabetes at baseline completed the follow-up evaluation ten years later (n = 191 cases). RESULTS: Unhealthy plant-based diet was significantly associated with likelihood for NAFL; the NAFL prevalence was 32.7%, 33.2% and 40.0%, respectively (p = 0.01), ranking from 1st to 3rd uPDI tertile. Multi-adjusted analysis revealed an inverse association between PDI and NAFL [OR(per 5 units increase in PDI) = 0.85 95%CI (0.76, 0.94)] and hPDI [HR(per 5 units increase in hPDI) = 0.91 95%CI (0.83, 0.99)] and a positive association in the case of uPDI [HR(per 5 units increase in uPDI) = 1.12 95%CI (1.01, 1.25)]. Multi-adjusted analysis revealed that baseline NAFL was associated with 2.95 times higher 10-year type 2 diabetes risk. No significant interaction of baseline liver steatosis with plant-based diet indices was observed (p for interaction > 0.05) in predicting type 2 diabetes. CONCLUSIONS: Plant-based diet quality is of importance for NAFL and affects long-term risk for incident type 2 diabetes.

Skeletal muscle mass and abdominal obesity are independent predictors of hepatic steatosis and interact to predict ten-year cardiovascular disease incidence: Data from the ATTICA cohort study.

BACKGROUND & AIMS: Sarcopenia and sarcopenic obesity may be associated with nonalcoholic fatty liver disease (NAFLD). This study examined the association between low skeletal muscle mass, with or without central obesity, with NAFLD, as well as their interaction on predicting 10-year incidence of cardiovascular disease (CVD). METHODS: This was a post-hoc analysis of the ATTICA study. At baseline, 3042 participants from the Attica region of Greece were recruited; 2020 completed the 10-year follow-up visit for CVD. NAFLD was assessed through hepatic steatosis index (HSI). Skeletal muscle mass index (SMI) was calculated to assess skeletal muscle mass. SMI was studied in tertiles, stratified by sex; the first tertile corresponds to the lowest SMI, the second to middle, and the third to highest SMI. Abnormal waist circumference was defined as ≥102 cm for men and ≥88 cm for women. The combined 10-year endpoint was the development of a fatal or nonfatal CVD event. Logistic regression analysis was used to assess the association between NAFLD prevalence and SMI as well as Cox regression analysis to assess the interaction of both variables on the incidence of CVD over 10 years. RESULTS: Higher rates of NAFLD were observed in the first (45%) compared to the second [33%; odds ratio (OR): 0.50, 95% confidence interval (95%CI): 0.41-0.61] and the third (22%; OR: 0.24, 95%CI: 0.19-0.29) SMI tertile. This association remained robust after multiple adjustments; significance was marginally lost, when waist circumference was added to the model. When SMI and waist circumference were evaluated jointly, participants with moderate/high SMI and normal waist circumference had the lowest and those with low SMI and abnormal waist circumference the highest NAFLD rate (24.3 and 60.5%, respectively; P < 0.001). Ten-year CVD incidence was gradually lower from the first (22.8%) to second (16.1%) and third SMI tertile (8.2%) (P < 0.001). The hazard ratio (HR) for the third vs. the first SMI tertile for predicting CVD in fully adjusted model was 0.69 (95%CI: 0.46, 1.00). The unadjusted HR for NAFLD predicting CVD was 3.00 (95%CI: 2.28-3.95). Finally, there was a significant interaction among NAFLD, SMI and waist circumference (P = 0.04) in determining the 10-year CVD incidence; the association between NAFLD and 10-year CVD remained significant for the participants with low SMI and normal or abnormal waist circumference, but not those with moderate/high SMI and normal or abnormal waist circumference. CONCLUSIONS: Increasing SMI and lower abdominal obesity are independently associated with lower rates of NAFLD, and the two interact as key determinants of NAFLD. Low SMI and central obesity are independent predictors of CVD and were shown to interact with NAFLD in determining 10-year CVD risk.

Quality of plant-based diets in relation to 10-year cardiovascular disease risk: the ATTICA cohort study.

PURPOSE: We prospectively evaluated the association between quality of plant-based diets and 10-year first fatal/non-fatal cardiovascular disease (CVD) incidence. METHODS: ATTICA study was conducted in the greater metropolitan Athens area, Greece, during 2001-2002 studying men and women (aged > 18 years old) free of CVD at baseline. Follow-up CVD assessment (2011-2012) was achieved in n = 2,020 participants (n = 317 cases). Dietary assessment was based on a validated semi-quantitative paper-based food frequency questionnaire. Overall, healthful, and unhealthful plant-based dietary indices (PDI, hPDI and uPDI) were calculated through a standard published procedure. The association between plant-based indices and CVD outcome has been evaluated via Cox regression analysis. RESULTS: The CVD event rate was 15.7% (n = 317) with a median follow-up time of 8.41 years. The highest (3rd PDI tertile) vs. lowest (1st tertile) adherence to plant-based pattern-irrespective to healthfulness of food products consumed-was inversely associated with CVD (hazard ratio (HR) 0.56; 95% confidence interval (95% CI) 0.14, 2.25) yet the CI was wide. Ranking from 1st to 2nd and 3rd hPDI tertile the CVD event rate was 6.4%, 10.5% and 16.2%, respectively (p = 0.003). Multi-variable adjusted analysis revealed that participants assigned in 2nd and 3rd hPDI tertile had 47% (HR 0.53; 95% CI 0.25-1.08) and 68% (HR 0.32; 95% CI 0.16-0.63) lower risk to develop CVD compared with their 1st tertile counterparts. Conversely, a positive association between uPDI and CVD risk was revealed in dose-response analysis (HR(per 5 units increase in uPDI) 1.34; 95% CI 0.95-2.37)). CONCLUSIONS: Quality of plant-based diets is important and needs to be considered, as not all plant-source foods have beneficial cardiovascular effects.

The presence of NAFLD influences the transition of metabolically healthy to metabolically unhealthy obesity and the ten-year cardiovascular disease risk: A population-based cohort study.

BACKGROUND/OBJECTIVES: We evaluated the role of the presence of non-alcoholic fatty liver disease (NAFLD) at baseline in the transition from metabolically healthy to metabolically unhealthy obesity (MHO to MUO) ten years later. METHODS: A prospective cohort study (ATTICA study, Greece) was performed between 2002 and 2012 studying a sample from the greater metropolitan Athens area. In total, 1514 (49·8%) men and 1528 (50.2%) women (aged >18 years old) free-of-CVD were included. Healthy metabolic status was defined as absence of all NCEP ATP III (2005) metabolic syndrome components. NAFLD was defined according to validated liver steatosis indices. Follow-up CVD assessment (2011-2012) was achieved in n = 2020 participants (n = 317 cases). RESULTS: NAFLD prevalence among MHO participants ranged from 29% to 39% according to the specific NAFLD score used. MHO participants who developed metabolically unhealthy status had about two times higher odds to have NAFLD at baseline compared with their metabolically healthy normal weight counterparts whereas stable MHO was not associated significantly with NAFLD. Moreover, MHO status accompanied by NAFLD was associated with increased CVD risk (Hazard Ratio = 2.90 95% Confidence Interval (1.35, 5.40)) in comparison to their non-NAFLD MHO counterparts. Further analysis revealed that in the obese, NAFLD indices and not simply visceral adiposity increased significantly the ability of metabolic status (using standard definition) to predict long-term CVD incidence. CONCLUSIONS: Considering NAFLD, even when assessed using validated indices only, in the clinical assessment of apparently healthy obese individuals predicts who is to develop MUO and contributes independently and more accurately to defining future cardiometabolic risk.

Predicted Skeletal Muscle Mass and 4-Year Cardiovascular Disease Incidence in Middle-Aged and Elderly Participants of IKARIA Prospective Epidemiological Study: The Mediating Effect of Sex and Cardiometabolic Factors.

The sex-specific effect of skeletal muscle mass (SMM) index (SMI) on 4-year first fatal/non-fatal cardiovascular disease (CVD) event in free-of-disease individuals was examined. In 2009, n = 1411 inhabitants (mean age = 64(12)) from Ikaria were selected. Follow-up was performed in 2013. SMI was created to reflect SMM through appendicular skeletal muscle mass (indirectly calculated through formulas) divided by body mass index (BMI). Fifteen and six tenths percent of participants exhibited CVD (19.8% in men/12% in women, p = 0.002). Significant U-shape trends were observed in participants >65 years old and women irrespective to age confirmed through multi-adjusted Cox regression analysis; in age >65 years, Hazard Ratio (HR)(2nd vs. 1st SMI tertile) = 0.80, 95% Confidence Interval (95%CI) (0.45, 0.96) and in women HR(2nd vs. 1st SMI tertile) = 0.71, 95% CI (0.33, 0.95), while, as for the 3rd SMI tertile, no significant trends were observed. Mediation analysis revealed that mediators of the aforementioned associations in men were the arterial distensibility and total testosterone, while, in women, inflammation, insulin resistance, and arterial distensibility. High SMM accompanied by obesity may not guarantee lower CVD risk. Specific cardiometabolic factors seem to explain this need for balance between lean and fat mass.

Peritoneal dialysis as a therapeutic solution in elderly patients with cardiorenal syndrome and heart failure: A case-series report.

BACKGROUND: The aim of this work was to evaluate the impact of peritoneal dialysis (PD) on venous congestion, right ventricular function, pulmonary artery systolic pressure (PASP), and clinical functional status in elderly patients with cardiorenal syndrome (CRS) and chronic heart failure (HF). METHODS: A case series of 21 (17 males, age 70 ± 11 years) consecutive patients with HF along with diuretic resistance and right ventricular dysfunction (median renal failure duration 60 months, range 13-287 months, mean ejection fraction 36 ± 11%) having been engaged in PD; 76% of the patients were under automated peritoneal dialysis (APD), whereas the rest were under continuous ambulatory PD (CAPD). Patients' PASP and central venous pressure (CVP) - through compression sonography - and body weight were evaluated before initiating the PD program and at 6 and 12 months. RESULTS: During the follow-up period, the mortality rate was 8 deaths out of 21 patients (38%) A significant reduction by 29.9% in PASP levels (p = 0.013) and by 42% in CVP levels (p < 0.001), and in right ventricular function assessed by tricuspid annulus tissue Doppler velocity (p = 0.04) was observed, whereas patients' weight increased by 3.7% (p = 0.001). New York Heart Association class improved in 12 patients, whereas in the remaining patients, it remained constant (p = 0.046). In 8 patients, complications were reported (mainly presence of Staphylococcus aureus). In conclusion, PD seems to confer a substantial benefit in clinical status, which is in line with improvement in venous congestion and right ventricular systolic pressure among elderly patients with HF along with CRS.

Prognostic value of exercise tolerance test for predicting cardiovascular disease in asymptomatic individuals with heterozygous familiar hypercholesterolemia.

Heterozygous familiar hypercholesterolemia (hFH) is an autosomal dominant inherited dyslipidemia, associated with premature cardiovascular disease (CVD). Aim of the study was to define prognostic factors for cardiovascular events (CVE) in asymptomatic individuals with hFH. All participants with recent diagnosis of hFH were recruited from the outpatient lipid clinic from 1987 to 2016, without any previous clinical evidence of CVD. A detailed clinical evaluation and laboratory investigation was obtained. Exercise tolerance test (ETT) was performed until maximum exercise capacity was achieved, without evidence of ischemia. Primary endpoint of the study was the first CVE. Four hundred fifty one participants were followed up for 10 ± 8 years, with 68 recorded cases of CVD (15%). Cumulative incidence of CVD was 15%, 24% and 32% for the 3 decades, respectively. In univariate analysis, male gender (p = 0.016), progression of age (p < 0.001), menopause (p = 0.030), waist-hip ratio (p = 0.043) and increased levels of Lp(α) (p = 0.014) were significantly associated with increased CVD incidence; whereas, exercise capacity (p = 0.025), low variation of heart rate (HR) during all stages of ETT compared to resting state (p = 0.020), maximum systolic (p = 0.014) and diastolic (p < 0.001) blood pressure were inversely associated with CVD. In multi-adjusted analysis, male gender (p < 0.001), duration of ETT (p = 0.023), estimated HR (p = 0.029), variation of HR during ETT compared to resting state (p < 0.05) and maximum diastolic pressure (p = 0.044) were significantly associated with CVD. Parameters of ETT in asymptomatic individuals with hFH, without any evidence of ischemia, may predict CVD in these high-risk patients after decades of observation.

The anti-inflammatory potential of diet and nonalcoholic fatty liver disease: the ATTICA study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is correlated with low-grade inflammation and dietary habits. Until today, there have been limited epidemiologic data assessing the role of diet's inflammatory potential on NAFLD. The aim was to evaluate the relationship between an anti-inflammatory diet, as reflected by the Dietary Anti-Inflammation Index (D-AII), and NAFLD among cardiovascular disease (CVD)-free adults. METHODS: ATTICA is a prospective, population-based study that recruited 3042 adults without pre-existing CVD from the Greek population (Whites; age ⩾18 years; 1514 men and 1528 women). D-AII was calculated using a standard procedure. The baseline study captured various sociodemographic, lifestyle and clinical characteristics as well as hepatic markers. These were used to calculate four NAFLD assessment indices: triglyceride-glucose (TyG) index, fatty liver index (FLI), hepatic steatosis index (HSI), and NAFLD Fatty Liver Score (NAFLD-FLS). Specific cutoffs were applied to capture NAFLD. RESULTS: D-AII showed a significant inverse association with NAFLD, applying the four indices with NAFLD cutoffs [odds ratio (OR) with 95% confidence interval (CI); TyG (0.95, 0.93-0.98); HSI (0.89, 0.86-0.92); FLI (0.88, 0.85-0.91); NAFLD-FLS (0.89, 0.86-0.92)], after adjusting for various confounders. Participants in the highest D-AII tertile had lower odds of having NAFLD, compared with those in the lowest D-AII tertile [(OR, 95% CI); TyG (0.33, 0.24-0.47); HSI (0.13, 0.08-0.23); FLI (0.05, 0.02-0.11); NAFLD-FLS (0.13, 0.07-0.23)]. Anti-inflammatory nutrition was related to lower odds of NAFLD among daily alcohol drinkers and individuals with metabolic syndrome. CONCLUSIONS: Anti-inflammatory diet is an important predictor of NAFLD among adults without pre-existing CVD. Adherence to a high anti-inflammatory diet seems to contribute to NAFLD prevention.

Dietary Patterns and Their Association with Anxiety Symptoms among Older Adults: The ATTICA Study.

Abstract: By 2050, the global population aged 60 years and over is expected to reach nearly 2.1 billion and affective disorders might be also expected to increase. Although nutrition has been related with affective disorders, there is a lack of studies assessing the relation between dietary habits and anxiety among European and Mediterranean older populations. In the present study, we aimed to evaluate the association between dietary habits, energy intake, and anxiety symptoms using data from 1128 Greek older adults (>50 years) without pre-existing cardiovascular disease (CVD) or any other chronic disease who participated in the ATTICA study. Various socio demographic lifestyle, bio-clinical (e.g., blood pressure), and psychological (e.g., depression) characteristics were used, and dietary habits as well as energy intake were calculated using standard procedures. Older people with anxiety were more likely to be sedentary, to be smokers, and to show symptoms of depression. The saturated fat and added sugars (SFAS) dietary pattern was associated with higher anxiety levels (non-standardized b (95% CI): 5.82 (0.03 to 11.61)). No association between energy intake tertiles and anxiety levels pictured in the later regression model. Moreover, female gender, family status, and depression were positively related to anxiety. Therefore, promoting healthy dietary habits could reduce anxiety symptoms of the older adults.

Vascular inflammation and metabolic activity in hematopoietic organs and liver in familial combined hyperlipidemia and heterozygous familial hypercholesterolemia.

BACKGROUND: Familial dyslipidemias of either heterozygous (heFH) or combined (FCH) type lead to accelerated atherogenesis and increased cardiovascular risk. OBJECTIVE: The aim of this study was to investigate in statin-naïve adult patients with familial dyslipidemias whether inflammatory activation and liver, spleen and bone marrow metabolic activity differ compared with normolipidemic subjects and between dyslipidemic groups. METHODS: Fourteen patients with FCH, 14 with heFH, and 14 normolipidemic individuals were enrolled. Serum lipids, high-sensitivity C-reactive protein, and fibrinogen levels were measured, followed by 18F-fluorodeoxyglucose positron-emission tomography/computed tomography imaging. Radiotracer uptake in the aortic wall, spleen, bone marrow, and liver was quantified as tissue-to-background ratio (TBR). RESULTS: Patients with heFH had significantly higher low-density lipoprotein levels compared with those with FCH and controls (P < .001). However, aortic TBRs were higher in FCH compared with heFH patients and controls (P = .02 and P < .001, respectively). FCH patients exhibited higher FDG uptake in the spleen compared with controls (P = .05). In addition, FCH exhibited higher bone marrow FDG uptake compared with heFH patients and controls (P = .03 and P = .02, respectively). FCH had higher liver uptake compared with heFH patients and controls (P < .001 for both). Significant correlations were observed between inflammatory biomarkers and imaging indices as well as between aortic TBR and FDG uptake of hematopoietic organs and liver. CONCLUSIONS: Systemic, as well as vascular inflammation and spleen, bone marrow, and hepatic metabolic activity are increased in patients with FCH despite lower levels of low-density lipoprotein.

Exercise capacity and haemodynamic response among 12,327 individuals with cardio-metabolic risk factors undergoing treadmill exercise.

Aims Haemodynamic parameters during and after exercise test seem to have a role in predicting cardiovascular events. We sought to evaluate the potential different responses in exercise capacity, heart rate and blood pressure levels in relation to major cardiovascular disease risk factors, among individuals undergoing exercise tolerance testing. Methods and results Consecutive individuals ( N = 12,327), aged 55 ± 11.8 years, underwent exercise tolerance testing, using the Bruce protocol. Obese participants showed higher values of peak systolic and diastolic blood pressure ( p < 0.01), with no heart rate differences. Diabetic patients presented increased systolic blood pressure across the test ( p = 0.02) and decreased tolerance to exercise ( p = 0.05), but without differences in diastolic blood pressure or heart rate. Hypertensives showed exaggerated blood pressure, chronotropic response and decreased capacity to exercise ( p < 0.001 for all). Smokers had increased baseline systolic blood pressure, peak diastolic blood pressure and recovery heart rate and decreased tolerance to exercise ( p < 0.001 for all). For all high-risk subgroups, exercise testing was more often positive. Age-stratified analysis revealed different patterns: all four risk factors significantly decreased peak metabolic equivalent in subjects <50 years old ( p < 0.05 for all), while in participants between 50 and 69 years old, diabetes mellitus ( p = 0.03), hypertension ( p = 0.04) and smoking ( p = 0.01) predicted achieved metabolic equivalent. For patients of ≥ 70 years old, obesity ( p = 0.006) and hypertension ( p = 0.02) decreased peak metabolic equivalent and systolic blood pressure recovery. In subjects without pre-existing cardiovascular disease and negative exercise tolerance testing (7064 subjects, mean age: 52.4 ± 12.1 years, 62.9% males), age, obesity, hypertension and female gender inversely and independently predicted peak metabolic equivalent. Conclusions High-risk individuals showed different haemodynamic responses when undergoing exercise tolerance testing, reflecting independent pathophysiological pathways.

Effects of Oral and Non-Insulin Injectable Antidiabetic Treatment in Hypertension: A Systematic Review.

BACKGROUND: Diabetes mellitus type 2 (T2DM) often co-exists with hypertension, and this aggregation of co-morbidities amplifies the risk for future cardiovascular events. Therefore, it appears crucial to understand the essence of choosing oral and non-insulin injectable anti-diabetic drugs (ADs) with a favorable hemodynamic impact that could partially attenuate the increased baseline cardiovascular risk. OBJECTIVE: We sought to evaluate the effect of ADs on blood pressure (BP) indices and to assess the potential role of certain ADs towards hypertension treatment. METHOD: We performed a systematic review of the literature searching MEDLINE via Pubmed for all human studies implementing ADs, either individually or in combinations. RESULTS: Metformin was found to reduce BP in small cohorts but failed to confirm its beneficial effect in a metaanalysis of 41 studies. Thiazolidinediones are associated with BP lowering but are contraindicated in patients with heart failure. Sulfonylureas, on the other hand, may increase BP, while a-glucosidase inhibitors, DPP-4 inhibitors, and SGLT2 inhibitors activate favorable pathophysiologic mechanisms serving as potential BP lowering agents. Relevant BP reduction was established for GLP-1 Ras in most clinical trials. CONCLUSION: The favorable hemodynamic impact of certain classes of ADs might provide synergistic or incremental therapeutic benefits in high-risk patients suffering from both T2DM and hypertension. Additional randomized trials designed under the hypothesis of the emerging beneficial hemodynamic effect of ADs are expected to provide more robust evidence and to guide the optimization of combined treatment strategies in this challenging group of patients.

Determinants of All-Cause Mortality and Incidence of Cardiovascular Disease (2009 to 2013) in Older Adults: The Ikaria Study of the Blue Zones.

AIM: Ikaria Island (North-East Aegean, Greece) has been recognized as one of the places with the highest life expectancy around the world (the Blues Zones). Risk factors in relation to 4-year all-cause mortality and cardiovascular disease (CVD) incidence in elders were studied. METHODS: From June to October 2009, 330 men and 343 women, aged 65 to 100 years, were enrolled, and in June to July 2013, they were reevaluated. RESULTS: Age-standardized, gender-specific, all-cause mortality rate was 790 deaths per 10 000 inhabitants, and causes of death were CVD (36%), cancer (21%), infection (10%), respiratory disease (2%), and other (31%). Incidence of CVDwas 520 cases per 10 000 men inhabitants and 320 cases per 10 000 women (P = .03). Age, male gender, heart rate, urea levels, left atrial maximum volume, left ventricular hypertrophy, thyroid-stimulating hormone, and moderate to severe depression were positively associated with mortality, whereas left ventricular ejection fraction as well as coffee and tea drinking, fruit intake, and exclusive olive oil use were inversely associated with CVD. CONCLUSION: Heart function markers in addition to antioxidant dietary factors were placed in this puzzle of CVD morbidity.

Chronotropic response during treadmill exercise and subclinical carotid atherosclerosis after adjusting for the calibrated SCORE risk classification: a cross-sectional study.

Carotid atherosclerosis (CA) and chronotropic incompetence (CI) during exercise are two independent cardiovascular risk factors. Aim of the current study was to investigate the possible association between them, in apparently healthy individuals, after adjusting for the 10-year cardiovascular disease (CVD) risk score. This cross-sectional study consisted of 139 apparently healthy subjects, 40-65 years old, who underwent treadmill exercise test (Bruce protocol used), which showed no evidence of ischemia. Heart rate reserve (HR reserve) was calculated to assess chronotropic response; a value of ≤ 0.80 is considered CI. CA was assessed by the presence of carotid plaque(s) in common and internal carotid arteries and carotid bulb bilaterally, using B-mode ultrasound. A calibrated version of SCORE (i.e., HellenicSCORE) was used to estimate the 10-year fatal CVD risk; participants were classified into low-, moderate- or high-risk group. CI was present in 7.9 % and CA in 18.7 % of the participants. After adjusting for 10-year CVD risk and other key confounders, odds of CA were 8.6 times higher in subjects with CI compared to their counterparts with normal chronotropic response to exercise. The results of the study indicate that CI during exercise can lead to high clinical suspicion of CA in apparently healthy individuals.

Statin therapy and risk of diabetes in patients with heterozygous familial hypercholesterolemia or familial combined hyperlipidemia.

OBJECTIVE: Controversial findings exist regarding potential influence of statin therapy on diabetic incidence. Aim of this study was to investigate the role of long duration statin treatment on diabetes mellitus (DM) incidence of Heterozygous Familial Hypercholesterolemia (hFH) and Familial Combined Hyperlipidemia (FCH) patients. METHODS: Study population consisted of 212 hFH and 147 FCH patients that visited Lipid Outpatient Department (mean follow up of 11 and 10 years respectively). Several clinical data such as history of DM, cardiovascular disease, thyroid function, metabolic syndrome, glucose levels, lipid profile and lifestyle data were obtained. In order to compare the effects of different doses of different types of statins, a "statin treatment intensity product" was used. RESULTS: 14% of FCH and only 1% of hFH patients developed DM during follow up. Although univariate analysis showed a statistical trend (p = 0.06) in the association between new onset DM and statin treatment intensity (STI) in the FCH subgroup of patients with normal baseline glucose levels, this was no longer significant after adjusting for several confounders. Furthermore, the type of statins used did not seem to play a role in the development of DM either in hFH or FCH patients. CONCLUSION: Long duration of high STI does not seem to be associated with diabetic risk in hFH patients. High STI used in the FCH population is not associated with increased risk of new onset DM compared to low STI. Further studies are required in order to clarify the potential diabetogenic effects of statins in these high risk populations.

Aortic elastic properties and cognitive function in elderly individuals: the Ikaria Study.

BACKGROUND: The aim of this work was to evaluate the association between aortic elastic properties and cognitive function in elderly individuals, permanent inhabitants of Ikaria Island. METHODS: In 535 individuals (75 ± 6 years, 53% males) aortic distensibility (AoD) was non-invasively calculated from the aortic diameters measured with echocardiography and brachial artery pressure using the formula by Stefanadis et al.; cognitive status was evaluated using the Mini Mental State Examination (MMSE). RESULTS: 88% of the elders had normal values of MMSE score (i.e., ≥ 24). Elders who achieved MMSE score ≥ 24 had higher values of AoD (1.90 ± 2.06 vs. 1.08 ± 1.42, p < 0.001), as well as were more physically active (85% vs. 69%, p = 0.05), had higher educational status (8.5 ± 2.8 years vs. 6 ± 2 years, p = 0.001), higher creatinine clearance levels (70 ± 21 vs. 63 ± 23, p = 0.05) and lower pulse pressure (PP) values (63 ± 16 vs. 68 ± 18, p = 0.06), as compared with those individuals with MMSE < 24. Logistic regression analysis showed that for every unit increase in AoD there was a 25% higher likelihood of having MMSE ≥ 24 (OR per 1000 × mmHg(-1) = 1.25, 95%CI 0.99-1.58), after adjustments for age, gender, current smoking, cardiovascular disease, creatinine clearance, hypertension, diabetes mellitus, obesity, physical activity status and education status. Furthermore having PP levels in the upper tertile (> 70 mmHg), increases by 55% the likelihood of having MMSE < 24 (OR for above 70 mmHg = 0.45, 95%CI 0.22, 0.92), after the same adjustments were made. CONCLUSION: Arterial aging seems to affect cognitive function; a finding that states a novel research hypothesis about the pathophysiological mechanisms of mental functioning.

Aortic artery distensibility shows inverse correlation with heart rate variability in elderly non-hypertensive, cardiovascular disease-free individuals: the Ikaria Study.

The aim of this study was to evaluate the relation between aortic artery distensibility, expressed by pulse pressure (PP) and autonomic nervous system function expressed by heart rate variability (HRV), among elders. During 2009, 469 individuals (50 % males, mean age 75 ± 6 years old), permanent inhabitants of Ikaria Island, were enrolled. Among several sociodemographic, bioclinical, lifestyle, and dietary characteristics, and biochemical parameters related to cardiovascular risk, a digital, standard, 12-lead electrocardiogram (ECG) and 5-min ECG monitoring were recorded. Smart ECG measurement and interpretation programs were used for the automated measurement and interpretation of ECG intervals. Autonomic nervous system tone was estimated with the HRV-standard deviation of normal to normal intervals (SDNN)-in surface ECG. Pulse pressure was calculated as the difference between systolic and diastolic blood pressures. Pulse pressure showed a positive association with age, systolic blood pressure levels, and presence of diabetes mellitus (all P < 0.001) and an inverse correlation with logSDNN. Multiadjusted logistic regression analysis revealed that 10-unit increase in SDNN values decreases by 26 % the likelihood of having PP above 70 mmHg; when the analysis was stratified according to hypertension status, the relationship remained significant only among non-hypertensive individuals. These data support the hypothesis that cardiac sympathovagal disturbance correlates with impaired elasticity properties of aorta, indicating parallel impairment in cardiac autonomic modulation and mechanical vessel wall properties in elderly non-hypertensive individuals.