Omentin, fat and heart: classical music with new instruments.

Obesity is a new pandemic and its cardiovascular and metabolic complications will be more evident in the near future. The need to elucidate the structure and function of adipose tissue is becoming more prominent. Body fat mass has long become not just a matter of quantification, but an area of great interest due to the paracrine, endocrine and autocrine properties of its elements. The novel adipokines are under intense investigation and omentin has come into the centre of interest due to its favourable effects on inflammation and glucose homeostasis. Not all aspects of omentin have been clarified. This review tries to focus on the current knowledge of these aspects and the future perspectives of this novel adipokine.

Testosterone therapy for functional hypogonadism in middle-aged and elderly males: current evidence and future perspectives.

Population aging is a global phenomenon driving research focus toward preventing and managing age-related disorders. Functional hypogonadism (FH) has been defined as the combination of low testosterone levels, typically serum total testosterone below 300-350 ng/dL, together with manifestations of hypogonadism, in the absence of an intrinsic pathology of the hypothalamic-pituitary-testicular (HPT) axis. It is usually seen in middle-aged or elderly males as a product of aging and multimorbidity. This age-related decline in testosterone levels has been associated with numerous adverse outcomes. Testosterone therapy (TTh) is the mainstay of treatment for organic hypogonadism with an identifiable intrinsic pathology of the HPT axis. Current guidelines generally make weak recommendations for TTh in patients with FH, mostly in the presence of sexual dysfunction. Concerns about long-term safety have historically limited TTh use in middle-aged and elderly males with FH. However, recent randomized controlled trials and meta-analyses have demonstrated safe long-term outcomes regarding prostatic and cardiovascular health, together with decreases in all-cause mortality and improvements in various domains, including sexual function, body composition, physical strength, bone density, and hematopoiesis. Furthermore, there are numerous insightful studies suggesting additional benefits of TTh, for instance in cardio-renal-metabolic conditions. Specifically, future trials should investigate the role of TTh in improving symptoms and prognosis in various clinical contexts, including sarcopenia, frailty, dyslipidemia, arterial hypertension, diabetes mellitus, fracture risk, heart failure, stable angina, chronic kidney disease, mood disorders, and cognitive dysfunction.

Integrating Machine Learning with Multi-Omics Technologies in Geroscience: Towards Personalized Medicine.

Aging is a fundamental biological process characterized by a progressive decline in physiological functions and an increased susceptibility to diseases. Understanding aging at the molecular level is crucial for developing interventions that could delay or reverse its effects. This review explores the integration of machine learning (ML) with multi-omics technologies-including genomics, transcriptomics, epigenomics, proteomics, and metabolomics-in studying the molecular hallmarks of aging to develop personalized medicine interventions. These hallmarks include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis. Using ML to analyze big and complex datasets helps uncover detailed molecular interactions and pathways that play a role in aging. The advances of ML can facilitate the discovery of biomarkers and therapeutic targets, offering insights into personalized anti-aging strategies. With these developments, the future points toward a better understanding of the aging process, aiming ultimately to promote healthy aging and extend life expectancy.

Nationwide mortality trends from 2001 to 2020 in Greece: health policy implications under the scope of aging societies.

OBJECTIVE: This nationwide study aims to analyze mortality trends for all individual causes in Greece from 2001 to 2020, with a specific focus on 2020, a year influenced by the COVID-19 pandemic. As Greece is the fastest-aging country in Europe, the study's findings can be generalized to other aging societies, guiding the reevaluation of global health policies. METHODS: Data on the population and the number of deaths were retrieved from the Hellenic Statistical Authority. We calculated age-standardized mortality rates (ASMR) and cause-specific mortality rates by sex in three age groups (0-64, 65-79, and 80+ years) from 2001 to 2020. Proportional mortality rates for 2020 were determined. Statistical analysis used generalized linear models with Python Programming Language. RESULTS: From 2001 to 2020, the ASMR of cardiovascular diseases (CVD) decreased by 42.7% (p < 0.0001), with declines in most sub-causes, except for hypertensive diseases, which increased by 2.8-fold (p < 0.0001). In 2020, the proportional mortality rates of the three leading causes were 34.9% for CVD, 23.5% for neoplasms, and 9.6% for respiratory diseases (RD). In 2020, CVD were the leading cause of death among individuals aged 80+ years (39.3%), while neoplasms were the leading cause among those aged 0-79 years (37.7%). Among cardiovascular sub-causes, cerebrovascular diseases were predominant in the 80+ year age group (30.3%), while ischemic heart diseases were most prevalent among those aged 0-79 years (up to 60.0%). CONCLUSIONS: The global phenomenon of population aging necessitates a reframing of health policies in our aging societies, focusing on diseases with either a high mortality burden, such as CVD, neoplasms, and RD, or those experiencing increasing trends, such as hypertensive diseases.

Advancing Cardiovascular Mortality Trend Analysis: A Machine Learning Approach to Predict Future Health Policy Needs.

This study investigates the forecasting of cardiovascular mortality trends in Greece's elderly population. Utilizing mortality data from 2001 to 2020, we employ two forecasting models: the Autoregressive Integrated Moving Average (ARIMA) and Facebook's Prophet model. Our study evaluates the efficacy of these models in predicting cardiovascular mortality trends over 2020-2030. The ARIMA model showcased predictive accuracy for the general and male population within the 65-79 age group, whereas the Prophet model provided better forecasts for females in the same age bracket. Our findings emphasize the need for adaptive forecasting tools that accommodate demographic-specific characteristics and highlight the role of advanced statistical methods in health policy planning.

A single-center, prospective, observational study on maternal smoking during pregnancy in Greece: The HELENA study.

INTRODUCTION: The unequivocal association between exposure to smoke and numerous complications of pregnancy, demonstrated in the last decades, has led to a significant decrease of smoking rates in pregnancy. The aim of the present study was to determine the prevalence of maternal smoking and to elucidate factors predisposing to it among pregnant women in Athens, Greece. METHODS: A population of 1700 pregnant women (mean age: 31.2±5.5 years) who visited consecutively the Cardiology Department of Helena Venizelou Maternity Hospital in Athens, Greece, between September 2016 and August 2017, was prospectively analyzed. Data regarding changes in the future mother's smoking habit as well as different sociodemographic factors potentially related to these changes were recorded. RESULTS: Of the 1700 participants, 704 (41.4%) were smokers, and of those 52.4% quit smoking after knowledge of their pregnancy status. The overall prevalence of smoking in pregnancy was 19.7%. Prevalence was higher in women who were aged <20 years (p=0.038), were multipara (p=0.032), had ≤12 years of education (p=0.044) and had a partner who was a smoker (p=0.047). Women aged ≤20 years were more likely to be persistent smokers at the beginning of pregnancy and demonstrated a higher prevalence of smoking during pregnancy (42.2% vs 19.7% in the overall study population). CONCLUSIONS: Our data demonstrate that maternal smoking during pregnancy still remains a major public health issue in Greece with a prevalence higher than most other industrialized countries.

MicroRNAs in Preeclampsia.

Preeclampsia (PE) continues to represent a worldwide problem and challenge for both clinicians and laboratory-based doctors. Despite many efforts, the knowledge acquired regarding its pathogenesis and pathophysiology does not allow us to treat it efficiently. It is not possible to arrest its progressive nature, and the available therapies are limited to symptomatic treatment. Furthermore, both the diagnosis and prognosis are frequently uncertain, whilst the ability to predict its occurrence is very limited. MicroRNAs are small non-coding RNAs discovered two decades ago, and present great interest given their ability to regulate almost every aspect of the cell function. A lot of evidence regarding the role of miRNAs in pre-eclampsia has been accumulated in the last 10 years. Differentially expressed miRNAs are characteristic of both mild and severe PE. In many cases they target signaling pathway-related genes that result in altered processes which are directly involved in PE. Immune system, angiogenesis and trophoblast proliferation and invasion, all fundamental aspects of placentation, are controlled in various degrees by miRNAs which are up- or downregulated. Finally, miRNAs represent a potential therapeutic target and a diagnostic tool.

Treatment with granulocyte colony stimulating factor is associated with improvement in endothelial function.

PRIMARY OBJECTIVE: Granulocyte-colony stimulating factor (G-CSF) is used for the mobilization of bone marrow and endothelial progenitor cells, though G-CSF-induced inflammation may cause endothelial dysfunction. We examined the effects of G-CSF on endothelium, C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-alpha) and anti-inflammatory cytokines namely interleukin 10 (IL-10). RESEARCH DESIGN: We studied 60 women with breast cancer, who were randomized to either subcutaneous G-CSF (5 microg/kg), o.d. for 5 days after adjuvant chemotherapy (n = 40) or placebo (n = 20). EXPERIMENTAL INTERVENTIONS: We measured flow-mediated dilatation (FMD%) of the brachial artery by ultrasonography, CRP, TNF-alpha, IL-10 and the ratio TNF-alpha/ IL-10 blood levels before, 2-h and 5-days after the G-CSF or placebo treatment. MAIN OUTCOMES AND RESULTS: There was a greater increase of FMD, IL-10 and reduction of TNF-alpha/ IL-10, 2 h and 5 days after the G-CSF treatment compared to placebo. Although, CRP and TNF-alpha were higher, TNF-alpha/IL-10 was lower at the end of G-CSF treatment compared to placebo. Improvement of FMD was related to changes of IL-10 and TNF-alpha/IL-10. CONCLUSIONS: Treatment with G-CSF improves endothelial function in vivo, possibly by shifting the balance between the pro- and anti-inflammatory cytokines.

Short-term effects of Mediterranean-type diet intervention on soluble cellular adhesion molecules in subjects with abdominal obesity.

BACKGROUND & AIMS: Abdominal obesity (AO) is associated with increased risk for cardiovascular disease and with increased production of adhesion molecules. The present work examined the effect of a Mediterranean-style diet on soluble cellular adhesion molecules in individuals with AO. METHODS: Ninety subjects with AO without cardiovascular disease or diabetes mellitus were randomly allocated to the intervention or control group and were instructed to follow a Mediterranean-style diet for two months. Intervention group followed a specific relevant food plan with close dietetic supervision and provision of basic foods. Soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), sP and sE-selectin, C-reactive protein (CRP) and interleukin-6 (IL-6) were measured. RESULTS: Subjects in the intervention group increased their intake of total fat, monounsaturated fatty acids, dietary fiber, vitamin C, and alcohol compared to controls, while decreased their intake of saturated fat. Although there was a significant decrease in CRP, sP-selectin and in sE-selectin in the intervention group, and an increase in sVCAM-1 in the control group, between-group analysis showed no statistically significant differences. There were also no significant changes in sICAM-1, and IL-6 levels after intervention. CONCLUSIONS: Mediterranean-type diet for two months combined with close dietetic supervision showed a beneficial tendency towards the down-regulation of some markers of vascular inflammation, although the comparison between groups after the intervention did not reach statistical significance. A longer period of dietary intervention may be required to further support these changes.

Long-term prognostic role of flow-mediated dilatation of the brachial artery after acute coronary syndromes without ST elevation.

Coronary endothelial vasodilator dysfunction is associated with increased cardiac events; the close relation between coronary vasomotor dysfunction and brachial artery vasoreactivity has been previously described. This study assessed the prognostic value of noninvasively assessed brachial artery vasoreactivity in survivors of acute coronary syndromes without ST-segment elevation. We examined 98 men (63.1 +/- 10.8 years) who were referred to our hospital for acute coronary syndromes without ST-segment elevation. Brachial artery endothelium-dependent flow-mediated dilation (FMD) and endothelium-independent nitrate-mediated dilation were examined in all patients using high-resolution echocardiographic Doppler ultrasound within 24 hours of admission. Plasma malondialdehyde, a marker of oxidative stress, and left ventricular ejection fraction were also assessed. Twenty-seven patients underwent coronary revascularization. Patients were followed for 24.8 +/- 5.9 months. Cardiovascular death, myocardial infarction, stroke, and unstable angina were designated as cardiovascular events (CEs). Twenty CEs were recorded. Kaplan-Meyer analysis showed that patients with FMD <1.9% (tertile 1 of FMD values) were more likely to have CEs than those with FMD >1.9% (log rank 5.29, p = 0.021). Multivariate Cox regression analysis showed that FMD <1.9% predicted CEs with an adjusted hazard ratio of 3.035 (95% confidence interval 1.148 to 8.023, p = 0.025) after adjustment for age, risk factors, troponin T, ejection fraction, revascularization procedures, number of diseased vessels, and medication. In conclusion, endothelium-dependent dilation of the brachial artery is a strong independent predictor of adverse outcome in survivors of acute coronary syndromes without ST-segment elevation.

Azilsartan as a Potent Antihypertensive Drug with Possible Pleiotropic Cardiometabolic Effects: A Review Study.

BACKGROUND: Hypertension related cardiovascular (CV) complications could be amplified by the presence of metabolic co-morbidities. Azilsartan medoxomil (AZL-M) is the eighth approved member of angiotensin II receptor blockers (ARBs), a drug class of high priority in the management of hypertensive subjects with diabetes mellitus type II (DMII). METHODS: Under this prism, we performed a systematic review of the literature for all relevant articles in order to evaluate the efficacy, safety, and possible clinical role of AZL-M in hypertensive diabetic patients. RESULTS: AZL-M was found to be more effective in terms of reducing indices of blood pressure over alternative ARBs or angiotensin-converting enzyme (ACE) inhibitors with minimal side effects. Preclinical studies have established pleiotropic effects for AZL-M beyond its primary antihypertensive role through differential gene expression, up-regulation of membrane receptors and favorable effect on selective intracellular biochemical and pro-atherosclerotic pathways. CONCLUSION: Indirect but accumulating evidence from recent literature supports the efficacy and safety of AZL-M among diabetic patients. However, no clinical data exist to date that evince a beneficial role of AZL-M in patients with metabolic disorders on top of its antihypertensive effect. Further clinical studies are warranted to assess the pleiotropic cardiometabolic benefits of AZL-M that are derived from preclinical research.

Cigarette smoking is associated with increased circulating proinflammatory and procoagulant markers in patients with chronic coronary artery disease: effects of aspirin treatment.

BACKGROUND: Smoking is associated with endothelial dysfunction. Cytokines released by injured endothelium promote vascular interactions with leukocytes and platelets. We investigated whether (a) cigarette smoking is linked to increased cytokine production, which may mediate platelet activation and thrombin generation in chronic coronary artery disease (CAD), and (b) aspirin treatment inhibits smoking-related changes on cytokines, platelets, and thrombin. METHODS AND RESULTS: Plasma macrophage-colony-stimulating factor (M-CSF) and C-reactive protein (CRP) were measured in 100 patients with chronic CAD, 60 of whom were chronic smokers. Prothrombin fragments 1+2 and urinary 11-dehydro-thromboxane B2 (TXB2) were additionally measured in 60 of 100 patients (30 of whom were smokers) and in 24 healthy controls. Smokers (n = 20) matched for age, myocardial ischemia, and other risk factors with 20 nonsmokers entered a double-blind crossover trial of aspirin (300 mg/d for 3 weeks) versus placebo. Blood and urine measurements were repeated after each treatment. Compared with nonsmokers, smokers had 3-fold median M-CSF (1499 vs 476 pg/mL), 2-fold CRP (1.5 vs 0.8 mg/L), and higher 11-dehydro-TXB 2 (3.6 vs 2.1 ng/mg creatinine, P < .01 for all comparisons). After aspirin treatment, M-CSF, CRP, 11-dehydro-TXB 2 , and prothrombin fragments 1+2 remained higher in smokers compared with nonsmokers despite a significant reduction of these markers by aspirin (P < .05). M-CSF remained related to 11-dehydro-TXB 2 excretion during both treatment phases (P < .01) suggesting that cytokine-mediated thromboxane A 2 production was not altered by aspirin. CONCLUSIONS: Smoking is associated with increased M-CSF, CRP, and platelet activity. Although aspirin treatment reduces the proinflammatory and procoagulant markers in smokers, it does not abolish the proinflammatory effects of smoking in patients with chronic CAD.

Novel antidepressant drugs, arterial hypertension and cardiovascular disease.

Depression is a common mental health issue worldwide leading to disability, functional decline and increased mortality. Novel antidepressants have been developed during the last decades in order to treat depression syndromes. Some evidence suggests that major depression has been associated with the development of congestive heart failure and with adverse outcomes in patients with coronary heart disease. The purpose of the present article is to review the impact of novel antidepressant patent drugs on cardiovascular disease and arterial hypertension.

Canagliflozin: a new hope in the antidiabetic armamentarium.

Canagliflozin-with the patent number WO2011142478A1- belongs to a novel class of antidiabetic drugs known as SGLT2 inhibitors, which has been approved by FDA in March 2013. This medication acts through the inhibition of glucose reabsorption in the kidney resulting in glucosuria and thus lowering of glucose blood levels. There are several phase III clinical ongoing trials involving this new class of medications. So far promising results have been shown. This review article summarizes current knowledge regarding the novel SGLT2 inhibitor canagliflozin and its future perspectives in the treatment of type 2 diabetes mellitus.

Close adherence to a Mediterranean diet improves endothelial function in subjects with abdominal obesity.

BACKGROUND: Abdominal obesity (AO) is associated with increased risk of cardiovascular disease and type 2 diabetes, whereas the Mediterranean diet exerts a cardioprotective effect. OBJECTIVE: We examined whether a close adherence to a Mediterranean-style diet improves endothelial function in individuals with AO. DESIGN: We recruited 90 subjects with AO without cardiovascular disease or type 2 diabetes. Participants were randomly assigned to the intervention or control group. Both groups were instructed to follow a Mediterranean-style diet for 2 mo. Subjects in the intervention group additionally had to follow a specific relevant daily and weekly food plan with close supervision by a dietitian and provision of basic foods. Flow-mediated dilatation (FMD), lipids, C-reactive protein (CRP), and insulin resistance with the homeostasis model assessment (HOMA-IR) were measured. RESULTS: After 2 mo, subjects in the intervention group increased their intake of total fat due to higher consumption of monounsaturated fatty acids as well as intakes of dietary fiber, vitamin C, and alcohol compared with the control group (all P < 0.05). The intervention group also increased FMD ( 2.05%; 95% CI: 0.97, 3.13%), whereas no effect was found in the control group (-0.32%; 95% CI: -1.31, 0.67%). Changes in lipids and CRP concentrations did not differ between the 2 groups, whereas diastolic blood pressure decreased in the intervention group (-6.44 mm Hg; 95% CI: -8.57, -4.31 mm Hg) compared with the control group (-0.76 mm Hg; 95% CI: -2.83, 1.31 mm Hg). Finally, there was a trend for a reduction in HOMA-IR in the intervention group compared with the control group (P = 0.072). CONCLUSION: Close adherence to a Mediterranean-style diet achieved by close dietetic supervision improves endothelial function in subjects with AO.

Inflammatory and non-invasive vascular markers: the multimarker approach for risk stratification in coronary artery disease.

Current thinking supports the notion that several inflammatory proteins intervene with endothelium and haemostatic factors leading to plaque formation and rupture. Of these, C-reactive protein (CRP), monocyte/macrophage colony-stimulating factor (MCSF) and interleukin-6 (IL-6) promote atherogenesis by inducing monocyte-macrophage activation, foam cell formation, platelet activation, tissue factor expression, release of other procoagulant cytokines or downregulation of atheroprotective cytokines such as interleukin 10 and transforming growth factor b-1 (TGFb-1). CRP, MSCF and IL-6 are interrelated and have been found in increased blood concentrations in CAD. Increased levels of CRP and IL-6 predict a higher cardiovascular event rate in the general population and in addition to high MCSF or low TGFb-1 predict adverse outcome in CAD patients independently of traditional risk factors. Moreover, in CAD patients, the predictive value of MCSF is additive and beyond that of CRP suggesting the need of a "multimarker approach" in assessing cardiovascular risk. Accumulating evidence supports the utility of non-invasive markers of subclinical atherosclerosis, namely carotid intimal media thickness, flow mediated dilatation of the brachial artery, augmentation index or pulse wave velocity, in the prediction of cardiovascular risk particularly in primary prevention settings. The combination of these non-invasive tests has been shown to improve their prognostic accuracy compared to each other alone. Although several therapeutic strategies like vaccination against antigens promoting atherogenesis, cyclooxygenase inhibitors, statins, and ACE inhibitors may reduce the levels of these inflammatory markers and improve the non-invasive markers of subclinical atherosclerosis, the impact on cardiovascular risk resulting from these changes is unknown. The combination of an established inflammatory marker such as CRP or a vascular marker such as IMT with novel biochemical and vascular markers of cardiovascular disease may offer additive prognostic information for adverse outcome.

Chronic administration of an angiotensin II receptor antagonist resets the hypothalamic-pituitary-adrenal (HPA) axis and improves the affect of patients with diabetes mellitus type 2: preliminary results.

Diabetes mellitus type 2 (DM type 2) is associated with depressive symptomatology and intermittent hyperfunction of the hypothalamic-pituitary-adrenal (HPA) axis. DM type 2 is also accompanied by increased tissue levels of angiotensin II (Ang II), which stimulates the HPA axis through the Ang II type 1 receptors (AT1). We investigated the effect of candesartan, an angiotensin receptor blocker (ARB) that crosses the blood brain barrier, on the activity of the HPA axis and on the affect of 17 patients with DM type 2, aged 40-65 years, who were treated with 4 mg/day candesartan per os for at least 3 months. Before and after candesartan administration, a corticotropin-releasing hormone (CRH) stimulation test and psychological tests were performed. In response to hCRH, time-integrated secretion of ACTH was not altered by candesartan administration, however, the cortisol response was decreased significantly compared to baseline (mean +/- SEM, 2327 +/- 148.3 vs. 1943 +/- 131.9 microg/dl, P = 0.005) suggesting reduced sensitivity of the adrenals to ACTH. In parallel, there was a significant improvement in interpersonal sensitivity (0.91 +/- 0.16 vs. 0.70 +/- 0.15, P = 0.027) and depression scores (0.96 +/- 0.15 vs. 0.71 +/- 0.10, P = 0.026). We suggest that candesartan resets the HPA axis of patients with DM type 2 and improves their affect.

IgA anticardiolipin antibody is associated with the extent of daily-life ischaemia in patients with chronic coronary artery disease.

BACKGROUND: Circulating anticardiolipin antibodies (aCL) may cause endothelial dysfunction. We investigated whether aCL are related to platelet activation, thrombin generation and daily-life ischaemia in patients with chronic coronary artery disease (CAD). METHODS: We measured (medians 25th-75th percentile) IgG, IgM, IgA aCL serum levels (Arbitrary Elisa Units, AEU), prothrombin fragments (F1+2, nmol/l), 24 h urine excretion of 11-dehydrothromboxane B2 (11-DHTXB2, ng/mg creatinine) creatine kinase (CK) and its cardiac isoenzyme CK-MB (IU/l) in 60 patients with angiographically documented CAD and in 40 age and sex matched controls. Patients underwent a 48 h Holter monitoring for assessment of the number and duration of ischaemic episodes. RESULTS: Patients had higher IgA-aCL levels than controls (3.2 vs 2.4 AEU, p = 0.002). Increased IgA-ACA levels were related to increased number and duration of ischaemic episodes (p<0.01). By ANOVA, patients with >or=10 ischaemic episodes (3rd tertile) or duration of ischaemia >or=32min (3rd tertile) had higher IgA-aCL than those with lower ischaemic burden (4.95 vs 3 vs 2.5 AEU, p = 0.002 and 4.9 vs 3 vs 2.5 AEU, p = 0.001 respectively). Patients with >or=2 ischaemic episodes (2nd and 3rd tertile) had higher 11-DHTXB2, than those with minimal ischaemia (2< episodes, 1st tertile) (p = 0.001). CK and CK-MB were within normal range after Holter monitoring. Receiver operating curve analysis showed a greater area under the curve for IgA-aCL than for 11-DHTXB2 in predicting severe ischaemia (>or=10 ischemic episodes or >or=32 min duration of ischaemia). CONCLUSION: Increasing IgA-aCL levels are associated with increasing ischemic burden in patients with CAD.

The relative impact of different measures of adiposity on markers of early atherosclerosis.

BACKGROUND: Although there are several methods available to assess adiposity, there is still controversy on the relative clinical utility of each of these methods. This study examines the relative impact of different measures of adiposity on markers of early atherosclerosis. In particular weight changes over time have been poorly assessed in this setting. METHODS: Eighty-six healthy individuals (31 men, age 36.5+/-8.9 years) with a wide range of body-mass index (28.7+/-7.0, 18.9-57.9 kg/m2) without hypertension, diabetes or smoking were examined. In addition to waist circumference and waist-to-hip ratio self-reported weight change since adolescence was also calculated. Ultrasonography was used to measure abdominal fat layers and their ratio. Flow-mediated dilatation of the brachial artery, serum levels of intercellular adhesion molecule (sICAM-1) and mean intima-media thickness of the carotid artery were measured as markers of early atherosclerosis. RESULTS: Stepwise multivariate regression analysis showed waist circumference and waist-to-hip ratio as the only independent predictor of flow-mediated dilatation. Waist circumference and weight change but not current body-mass index were independent predictors of intima-media thickness. These correlations were not influenced by ultrasonographically measured fat layers, C-reactive protein and basal insulin resistance. Body-mass index and weight gain were associated with sICAM-1 but not independently of basal insulin resistance and C-reactive protein. CONCLUSIONS: Waist circumference and weight gain were the strongest predictors of early atherosclerosis in a population of apparently healthy adults. The ultrasonographically measured fat layers did not provide additional information in this population.

Divergent effects of rofecoxib on endothelial function and inflammation in acute coronary syndromes.

BACKGROUND: The safe use of selective inhibitors of cyclooxygenase-2 in patients with cardiovascular disease has been questioned because of studies showing an increased risk of cardiac events. We examined the short-term effect of rofecoxib, a selective cyclooxygenase-2 inhibitor, on endothelial function, oxidative damage and inflammation in patients with acute coronary syndromes without ST-segment elevation. METHODS: Forty-three patients with acute coronary syndromes without ST-segment elevation participated in the study. Flow-mediated dilatation (FMD), nitrate-mediated dilatation (NMD) of the brachial artery, malondialdehyde, a marker of lipid peroxidation, C-reactive protein, an acute phase marker of inflammation, and interleukin-6, a proinflammatory cytokine, were measured within 24 h of admission and a week later. Patients were randomized to receive for a week 100 mg aspirin daily with either 25 mg of rofecoxib (n=21) or placebo (n=22) orally once daily. RESULTS: Malondialdehyde, C-reactive protein and interleukin-6 levels were reduced in the rofecoxib group (p=0.04, p=0.003 and p=0.02 respectively) while they remained unchanged in the placebo group after 1 week of treatment. FMD and NMD changes in both groups were not statistically different. CONCLUSIONS: Co-administration of rofecoxib with low-dose aspirin decreases inflammatory and oxidative indices but does not improve endothelial function. The lack of improvement in FMD despite the improvement in inflammation and oxidative stress could be viewed in association to the recent observations on the adverse effects of COX-2 inhibition on the cardiovascular system.