The Ryanodine Receptor Leak: Its Role in the Development of Heart Failure

The cardiac ryanodine receptor-Ca2+ release channel (RyR2) is an essential sarcoplasmic reticulum (SR) transmembrane protein that plays a central role in excitation-contraction coupling in cardiomyocytes. Aberrant spontaneous, diastolic Ca2+ leak from the SR due to dysfunctional RyR2 is the mechanism underlying contractile and relaxation dysfunctions in heart failure. Several potential mechanisms have been proposed to explain the dysfunctional RyR2 in heart failure including overphosphorylation status of RyR2, altered RyR2 regulation and perturbed RyR2 intra/intermolecular interactions. Novel therapeutic strategies that enhance myocyte Ca2+ homeostasis could prevent and reverse adverse cardiac remodeling and improve clinical outcomes in patients with heart failure

Long-term prognostic value of LDL-C, HDL-C, lp(a) and TG levels on cardiovascular disease incidence, by body weight status, dietary habits and lipid-lowering treatment:the ATTICA epidemiological cohort study (2002–2012)

BACKGROUND: The link between blood lipids and cardiovascular disease (CVD) is complex. Our aim was to assess the differential effect of blood lipids on CVD risk according to age, sex, body weight, diet quality, use of lipid-lowering drugs and presence of hypercholesterolemia. METHODS: In this secondary analysis of the ATTICA prospective cohort study, serum blood lipids, i.e., total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) and liproprotein(a) [Lp(a)], and sociodemographic, anthropometric, lifestyle and clinical parameters were evaluated at baseline (2001/2002) in 2020 CVD-free men and women. CVD incidence was recorded at the 10-year follow-up (2011/2012). RESULTS: All blood lipids assessed were univariately related to CVD risk; however, associations remained significant only for HDL-C and TG in multivariate models adjusted for age, sex, body mass index, smoking, Mediterranean Diet Score, physical activity, presence of hypercholesterolemia, hypertension and diabetes mellitus, use of lipid-lowering drugs, and family history of CVD [RR per 1 mg/dL (95% CI): 0.983 (0.967, 1.000) and 1.002 (1.001, 1.003), respectively]. In stratified analyses, TC and LDL-C predicted CVD risk in younger subjects, normal-weight subjects, and those not on lipid-lowering drugs, while HDL-C and TG were significant predictors in older subjects, those with low adherence to the Mediterranean diet, and hypercholesterolemic subjects; a significant effect on CVD risk was also observed for TG in males, overweight participants and lipid-lowering medication users and for Lp(a) in older subjects and females (all p ≤ 0.050). CONCLUSIONS: The impact of blood lipids on CVD risk differs according to several biological, lifestyle and clinical parameters

The association between serum uric acid levels and 10-year cardiovascular disease incidence: results from the ATTICA prospective study.

Limited data suggests possible gender-specific association between serum uric acid (SUA) and cardiovascular disease (CVD) incidence. The aim of the present analysis was to evaluate the association between SUA levels and 10-year CVD incidence (2002-2012) in the ATTICA study participants. Overall, 1687 apparently healthy volunteers, with SUA measurements, residing in the greater metropolitan Athens area (Greece), were included. Multivariable Cox-regression models were used to estimate the hazard ratios for SUA in relation to 10-year CVD incidence. Receiver operating curve analysis was conducted to detect optimal SUA cut-off values. Participants in the 2nd and 3rd SUA tertile had 29 and 73% higher 10-year CVD incidence compared with those in the 1st tertile (p < 0.001). In gender-specific analysis, only in women SUA was independently associated with CVD incidence; women in the 3rd SUA tertile had 79% greater 10-year CVD event risk compared to their 1st tertile counterparts. Obese in the 3rd SUA tertile had 2-times higher CVD incidence compared to those in the 1st tertile. Similar findings were observed in metabolically healthy (vs. unhealthy) and metabolically healthy obese. SUA thresholds best predicting 10-year CVD incidence was 5.05 and 4.15 mg/dL (0.30 and 0.25 mmol/L) in men and women, respectively. In conclusion, increased SUA levels were independently related to 10-year CVD event rate in women, obese and metabolically healthy individuals. SUA could predict 10-year CVD incidence even at low levels. Further studies are warranted to identify SUA cut-off values that may improve the detection of individuals at higher CVD risk in clinical practice

Exposure to second hand smoke and 10-year (2002–2012) incidence of cardiovascular disease in never smokers: The ATTICA cohort study

Background: Despite WHO Framework Convention of Tobacco Control (FCTC) adoption, effective implementation of national smoking bans remains pending in several countries. This study quantified the association of second hand smoke (SHS) exposure and 10-year cardiovascular disease (CVD) among never smokers in such settings. Methods: In 2001–2002, a sample of 1514 males and 1528 females (range: 18–89 years old) were randomly selected in Greece. Frequency and duration of SHS exposure (i.e. exposure extending \u3e30 min/day) within the home and/or workplace were assessed by interview. Following a 10-year follow-up period (2002–2012), incidence of non-fatal and fatal CVD (ICD-10) was evaluated among n = 2020 participants. The analytic study sample consisted of all never smokers (n = 910). Results: Despite national smoking ban implementation (2009), 44.6% (n = 406) of never smokers reported SHS exposure. While SHS exposed never smokers exhibited a more favorable profile of CVD-related risk factors at baseline, they subsequently developed similar 10-year CVD incidence rates, at a younger mean age (p = 0.001), than their non-exposed counterparts. Following adjustment for several lifestyle and clinical factors, SHS exposed never smokers exhibited a two-fold elevated 10-year CVD risk (adj. HR: 2.04, 95% CI: 1.43–2.92), particularly among women (adj. HR: 2.45, 95% CI: 1.45–4.06). SHS exposure accounted for 32% excess Population Attributable Risk (PAR) for 10-year CVD events in never smokers, with highest rates (PAR: 52%) being among those exposed in the workplace. Conclusion: The prevention of SHS associated CVD and related healthcare costs mandates additional strategies for securing the effective implementation of comprehensive WHO FCTC based national smoking bans

Sociodemographic and Lifestyle Statistics of Oldest Old People (>80 Years) Living in Ikaria Island: The Ikaria Study

Background. There are places around the world where people live longer and they are active past the age of 100 years, sharing common behavioral characteristics; these places (i.e., Sardinia in Italy, Okinawa in Japan, Loma Linda in California and Nicoya Peninsula in Costa Rica) have been named the “Blue Zones”. Recently it was reported that people in Ikaria Island, Greece, have also one of the highest life expectancies in the world, and joined the “Blue Zones”. The aim of this work work was to evaluate various demographic, lifestyle and psychological characteristics of very old (>80 years) people participated in Ikaria Study. Methods. During 2009, 1420 people (aged 30+) men and women from Ikaria Island, Greece, were voluntarily enrolled in the study. For this work, 89 males and 98 females over the age of 80 yrs were studied (13% of the sample). Socio-demographic, clinical, psychological and lifestyle characteristics were assessed using standard questionnaires and procedures. Results. A large proportion of the Ikaria Study's sample was over the age of 80; moreover, the percent of people over 90 were much higher than the European population average. The majority of the oldest old participants reported daily physical activities, healthy eating habits, avoidance of smoking, frequent socializing, mid-day naps and extremely low rates of depression. Conclusion. Modifiable risk factors, such as physical activity, diet, smoking cessation and mid-day naps, might depict the “secrets” of the long-livers; these findings suggest that the interaction of environmental, behavioral together with clinical characteristics may determine longevity. This concept must be further explored in order to understand how these factors relate and which are the most important in shaping prolonged life

Adherence to the Mediterranean diet moderates the association of aminotransferases with the prevalence of the metabolic syndrome; the ATTICA study

<p>Abstract</p> <p>Background</p> <p>Elevated liver enzymes are markers of liver steatosis and metabolic syndrome. We aimed to investigate the association of Mediterranean diet on the relationship between aminotransferases (i.e., AST, ALT, gGT) and the metabolic syndrome.</p> <p>Methods</p> <p>The ATTICA study has randomly enrolled 1514 adult males (18–87 yrs) and 1528 females (18–89 yrs) from the greater area of Athens. Adherence to Mediterranean diet was assessed through the MedDietScore. According to NCEP III criteria, participants were classified into those with or without the metabolic syndrome.</p> <p>Results</p> <p>Women with metabolic syndrome had higher γGT (p = 0.02) and lower AST/ALT levels (p = 0.018) than those without, and men with metabolic had a lower AST/ALT ratio (p = 0.01) compared to those without metabolic syndrome. The AST/ALT ratio was also positively correlated with MedDietScore (rho = 0.17, <it>p </it>< 0.001), while higher MedDietScore was associated with lower likelihood of having the metabolic syndrome in a multi-adjusted analysis (OR = 0.34, 95% CI: 0.16–0.73). Stratified analysis by the level of adherence to the Mediterranean diet, revealed that only in subjects away or with moderate adherence to the Mediterranean diet, an increase in the AST/ALT ratio was associated with lower likelihood of having the metabolic syndrome (OR = 0.33, <it>p </it>< 0.05 and OR = 0.34, <it>p </it>< 0.09, respectively); however, when we focused in those with greater adherence to the Mediterranean diet, AST/ALT ratio was not associated with the presence of the syndrome (OR = 0.51, <it>p </it>= 0.55). These findings remained similar in both genders, and even when the quantity of alcohol drinking was taken into account.</p> <p>Conclusion</p> <p>Aminotransferases ratio constitutes a marker of the metabolic syndrome among healthy adults; however, this relationship is moderated when individuals are close to the Mediterranean dietary pattern.</p

Abdominal obesity, blood glucose and apolipoprotein B levels are the best predictors of the incidence of hypercholesterolemia (2001–2006) among healthy adults: the ATTICA Study

<p>Abstract</p> <p>Objective</p> <p>In this work we evaluated the 5-year incidence of hypercholesterolemia, in a sample of cardiovascular disease free adult men and women from Greece. We also evaluated the association of several socio-demographic, dietary and lifestyle habits on the incidence of this disorder.</p> <p>Methods</p> <p>1514 men and 1528 women (>18 y) without any clinical evidence of cardiovascular disease, living in Attica area, Greece, were enrolled in the ATTICA study from May 2001 to December 2002. The sampling was random, multi-stage, and included information about various socio-demographic, lifestyle (diet, exercise, smoking etc), biological (lipids, and inflammatory markers), and clinical characteristics of the participants. In 2006, a group of experts performed the 5-year follow-up through telephone calls or personal visits (941 of the 3042 (31%) participants were lost to follow-up). Hypercholesterolemia, among people who had normal blood lipids at initial examination, was defined as fasting total cholesterol levels > 200 mg/dl or use of lipids lowering agents (NCEP ATPIII).</p> <p>Results</p> <p>The 5-year incidence of hypercholesterolemia was 23.7% (n = 127) in men and 17.7% (n = 110) in women (p for gender differences < 0.001). Multi-adjusted logistic regression analysis which revealed that increased age (odds ratio = 1.05, p < 0.001), waist circumference (odds ratio = 1.02, p = 0.03), fasting blood glucose (odds ratio = 1.01, p = 0.08) and apolipoprotein B (odds ratio = 1.02, p = 0.001) levels, were the most significant baseline predictors of developing hypercholesterolemia within a 5-year period.</p> <p>Conclusion</p> <p>Incidence of hypercholesterolemia was high in both genders, emphasizing the burden of this disorder at population level. Aging, increased waist circumference, fasting blood glucose and apolipoprotein B levels were the most significant baseline predictors of hypercholesterolemia.</p

Consumption of fruits and vegetables in relation to the risk of developing acute coronary syndromes; the CARDIO2000 case-control study

BACKGROUND: The relation between diet and human health has long been investigated. The aim of this work is to evaluate the association between CHD risk and the consumption of fruit and vegetable, in a large sample of cardiac patients and controls. METHODS: Stratified sampling from all Greek regions, consisted of 848 (700 males, 58 ± 10 years old and 148 females, 65 ± 9 years old) randomly selected patients, admitted to the cardiology clinic for a first event of an acute coronary syndrome (ACS). In addition we selected 1078 frequency paired, by sex-age-region, controls in the same hospitals but without any clinical suspicion of CHD. Using validated food-frequency questionnaires we assessed total diet, including fruit and vegetable intake, on a weekly basis. Multiple logistic regression analysis estimated the relative risk of developing ACS by level of fruits and vegetables intake after taking into account the effect of several potential confounders. RESULTS: Data analysis revealed that the benefit of fruit or vegetable consumption increases proportionally by the number of servings consumed (P for trend < 0.001). After adjusting for the conventional cardiovascular risk factors, those in the upper quintile of fruit consumption (5 or more items/day) had 72% lower risk for CHD (odds ratio = 0.28, 95% CI 0.11 – 0.54, P < 0.001), compared with those in the lowest quintile of intake (<1 items/day). Similarly, consumption of vegetable more than 3 days / week was associated with 70% lower risk for CHD (odds ratio = 0.30, 95% CI 0.22 – 0.40, P < 0.001), compared with those that they did not consume vegetables. Of particular interest, a 10% reduction in coronary risk was observed for every one piece of fruit consumed per day (odds ratio = 0.90, 95% CI 0.85 – 0.97, P = 0.004). CONCLUSIONS: Consumption of fruits and vegetables seems to offer significant protection against CHD