Heartscore calculated in individuals younger than 40 years is related to vascular markers of early atherosclerosis.

BACKGROUND: Heartscore is not well validated for individuals less than 40 years of age. In the latest guidelines a relative risk chart is provided with the proposal to be used for young adults aged less than 60 years instead of projecting risk at the age of 60 years. Moreover, coronary artery disease is insidiously manifested in younger patients. DESIGN: Cross-sectional study. METHODS: Two hundred and two young Greeks of age less than 40 years and 232 middle-aged adults aged 40-60 years without clinically overt cardiovascular disease or diabetes were consecutively recruited. Flow-mediated dilatation of the brachial artery, carotid, and femoral intima media thickness (IMT), carotid-radial and carotid-femoral pulse wave velocity (PWV) were measured in all individuals in one session. The European Society of Cardiology online Heartscore calculator was used for mortality risk (MR) 60 and Systematic Coronary Risk Evaluation risk charts for relative risk (RR) computation. RESULTS: MR60 in the younger significantly correlated with all measured vascular markers whereas RR significantly correlated with carotid IMT. By multivariate regression analysis, MR60 was a stronger identifier than RR for PWV, mean carotid and femoral IMT in both groups. Young adults (<40 years) with a high MR60 (>5%) had significantly higher carotid-radial PWV, carotid and femoral IMT whereas those with a high RR (>3rd tertile) had significantly higher carotid IMT. CONCLUSION: MR60 was a stronger identifier of most of the measured markers of early atherosclerosis as compared with RR. These data support Heartscore as a prognostic tool in terms of primary prevention for participants younger than 40 years old.

Postprandial improvement of endothelial function by red wine and olive oil antioxidants: a synergistic effect of components of the Mediterranean diet.

OBJECTIVE: Consumption of olive oil may cause postprandial impairment of endothelial function, while acute ingestion of red wine seems to improve it. The purpose of the present study was to investigate the combined postprandial effects of two essential components of the Mediterranean diet, red wine and olive oil, on endothelial function. METHODS: Fifteen healthy subjects were enrolled in the study, which was comprised of 4 study days. Subjects were asked to consume a standard meal at each study day containing 50 gr of olive oil and 250 ml of wine. Two types of wine (red and white; rich and poor in antioxidants respectively) and two types of olive oil (green and refined; rich and poor in antioxidants respectively) were used in a 2*2 design. Endothelium dependent, flow mediated dilatation (FMD) was measured with a B-Mode ultrasound device at fast and 1, 2 and 3 hours postprandially. RESULTS: Combined consumption of red wine and green olive oil (both rich in antioxidants) improved FMD postprandially (p = 0.002, ANOVA for repeated measures), which remained significant 1 hour (p = 0.002) and 2 hours (0.037) following the meal compared to fasting levels. No other combination of wine and olive oil caused any significant alteration on FMD. CONCLUSION: Acute consumption of both red wine and green olive oil, rich in antioxidants, led to an improvement in the postprandial endothelial function in healthy subjects. These findings provide an additional favorable effect of components of the Mediterranean diet and of their antioxidant substances on endothelial function, at the postprandial state.

Tuberculosis in patients with systemic rheumatic or pulmonary diseases treated with glucocorticosteroids and the preventive role of isoniazid: a review of the available evidence.

Development of tuberculosis (TB) is a concern in patients who receive glucocorticosteroids for the treatment of chronic rheumatic or pulmonary diseases. However, the incidence of development of TB in such patients and the prophylactic role of isoniazid (INH) are unclear. We evaluated the available evidence from 20 relevant prospective and retrospective cohort and case-control studies identified in the PubMed and Cochrane databases. The frequency of development of TB in the populations studied varied from 0% to 13.8%. This figure was low in studies performed in countries with a low incidence of TB (0% in the USA and Greece, 0.6% in France and 1.35% in Spain). In contrast, the frequency of development of TB in the studied cohorts was high in studies performed in countries with a moderate to high incidence of TB (from 2.5% in South Korea to 13.8% in The Philippines). Isoniazid prophylaxis (INHP) was found to decrease the incidence of development of TB in two of four studies that examined this intervention. The available evidence suggests that patients who receive steroids for the treatment of chronic rheumatic or pulmonary diseases and who live in countries with a high incidence of TB have a high risk of development of TB in contrast to patients who live in countries with a low incidence of the infection. However, the role of INHP even for patients living in countries where TB is endemic is unclear because the effectiveness of INH in preventing TB development in such patients is not well established and there are cost-effectiveness and safety issues.

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.

Eating frequency predicts new onset hypertension and the rate of progression of blood pressure, arterial stiffness, and wave reflections.

BACKGROUND: Cross-sectional evidence indicates that eating frequency correlates with blood pressure, hypertension, and related target organ damage. The aim of the present study was to prospectively assess eating frequency as a predictor of arteriosclerosis progression and new onset hypertension over a follow-up period of 5 years in adults without cardiovascular disease. METHODS: Eating frequency among other dietary parameters was evaluated in 115 nondiabetic study participants from a general population sample (54 ±â€Š9.1 years, 45 women) at a baseline visit. Metabolic parameters known to be associated with eating frequency, markers of arteriosclerosis, including augmentation index, pulse wave velocity, SBP, and DBP were evaluated in all volunteers at baseline and after a 5-year follow-up. RESULTS: By applying linear mixed models analysis, it was found that a high eating frequency at baseline significantly correlated with the rate of progression of pulse wave velocity (ß = 0.521, P = 0.004), augmentation index (ß = 0.503, P = 0.01), SBP (ß = 0.694, P < 0.001), and DBP (ß = 0.477, P = 0.009) and the incidence of new onset hypertension (odds ratio = 8.89, P < 0.001). After adjustment traditional cardiovascular risk factors, heart rate, homeostasis model assessment index of insulin resistance and total energy intake, the associations with augmentation index, SBP, DBP, and new onset hypertension remained significant. CONCLUSION: In a population of nondiabetic adults without cardiovascular disease, eating frequency is associated with the rate of progression of wave reflections, blood pressure and of new onset hypertension. Interventional studies should confirm these data and possibly further assess the utility of eating behavior in the prevention of new onset hypertension and related target organ damage.

Meal patterns in healthy adults: Inverse association of eating frequency with subclinical atherosclerosis indexes.

BACKGROUND & AIMS: Meal patterns and their relationship with cardiovascular disease are insufficiently examined with important clinical implications. Our aim was to investigate associations between eating frequency (EF) and early markers of atherosclerosis. METHODS: In this cross-sectional study, we consecutively recruited 164 healthy subjects (46.8 ± 9.3years, 62 men). EF among other dietary parameters and markers of subclinical atherosclerosis, including flow mediated dilatation (FMD), pulse wave velocity (PWV), intima media thickness (IMT) and the presence of plaques in the carotid arteries were evaluated in all volunteers. RESULTS: EF was positively associated with total energy intake (EI) and a favorable profile in terms of adiposity, glucose tolerance and blood lipids. Subjects with an increased EF (> median), had significantly lower IMT (p = 0.024) and prevalence of plaques (5.3% vs. 21.3%, p = 0.003), as compared to those below median. IMT and the prevalence of plaques were also significantly lower in those with increased EF compared with subjects with low EF belonging to the same group of energy intake (EI) by EI median. By multivariate regression analysis, carotid plaques remained significantly associated with EF (OR: 0.71, 95% CI 0.56-0.89), while IMT also remained significantly associated with EF after adjustment for age and dietary factors (beta: -0.010, 95% CI: -0.020 to -0.0002), but not after adding obesity-related risk factors. CONCLUSION: Increased EF is associated with lower prevalence of subclinical atherosclerosis in the carotid arteries in apparently healthy individuals. Whether consumption of the same amount of energy in more eating episodes favorably affects cardiovascular risk should be further investigated.

Association of the SHBG gene promoter polymorphism with early markers of atherosclerosis in apparently healthy women.

OBJECTIVE: Androgen may be detrimental in the development of cardiovascular disease in women. We investigated possible associations between the (TAAAA)n polymorphism of sex hormone binding globulin (SHBG) gene promoter, which influences transcriptional efficiency of the SHBG gene - and thus the tissue androgen availability - and early markers of atherosclerosis in apparently healthy women. DESIGN AND METHODS: In this prospective clinical study, 153 consecutive women (mean age 43.9±9 years, 66 of whom postmenopausal, without known diabetes, cardiovascular disease), visiting our internal medicine outpatients were examined for unrecognised features of the metabolic syndrome. Endothelium dependent vasodilatation (FMD) and intima media thickness of the common carotid artery (IMT) were recorded. According to the number of SHBG gene promoter repeats patients were classified as short (≤7), medium (=8) and long repeat (≥9) allele groups. RESULTS: The (TAAAA)n repeat length was an independent predictor of FMD in multivariate analysis (p<0.03). FMD was positively correlated with SHBG levels (p=0.004). Women carriers of two long alleles had increased IMT (p=0.031) although this was not independent in the multivariate analysis. CONCLUSIONS: Longer (TAAAA)n repeats in the SHBG gene promoter are associated with impaired FMD, which is an early marker of atherosclerosis. As this polymorphism has been associated with a more androgenic phenotype in women, this association may reflect the life-long tissue exposure to higher free androgens and indirectly supports the view that androgenic exposure may have adverse cardiovascular effects in women.

Endogenous estrogen levels are associated with endothelial function in males independently of lipid levels.

Estrogens and androgens may play an important role in vascular health in both sexes. The aim of this study was to examine the relation of endogenous sex hormone levels with early markers of atherosclerosis in a cohort of apparently healthy males. 124 males (age 46.25 ± 9.56) attending a preventive medicine program were examined for unrecognised features of the metabolic syndrome. Flow-mediated dilatation (FMD) and intima-media thickness (IMT) of the common carotid artery were evaluated. Obesity parameters were recorded; estradiol, testosterone, SHBG, free testosterone, insulin, as well as glucose and lipid levels were measured. FMD was positively correlated with estradiol (r = 0.201, P = 0.041) and negatively with total cholesterol (r = -0.205, P = 0.022), low density lipoproteins (r = -0.232, P = 0.009), and triglyceride levels (r = -0.179, P = 0.046). In multivariate analysis, the association of FMD with estrogen was independent of BMI and lipid levels. No significant association between FMD and testosterone levels was found. Subjects with an increased mean IMT (> 0.73 mm, i.e., > 3rd tertile) had lower levels of free (P = 0.021) and bioavailable (P = 0.016) testosterone. In multivariate logistic regression analysis, this association was no longer significant when age or cholesterol levels were considered. Endogenous estrogen levels are associated with FMD, independently of age and lipid levels, showing a protective effect in middle-age male subjects. Circulating androgens are associated, although not independently, with structural changes such as the IMT of carotid artery; this effect is possibly influenced by lipid levels and age.

Free thyroxine is an independent predictor of subcutaneous fat in euthyroid individuals.

OBJECTIVE: Thyroid function parameters have been associated with obesity, but associations with the type of adiposity have not been examined. We used ultrasound (US) to assess regional adiposity and investigated associations of thyroid function with parameters of central obesity. DESIGN: Cross-sectional study. METHODS: A total of 303 apparently healthy individuals (age 42.9+/-8.8, body mass index (BMI) 19.0-43.3, median 26.2 kg/m(2), 181 women) were examined for indices of the metabolic syndrome. BMI, waist and hip circumference, abdominal subcutaneous fat (SF), and preperitoneal fat (PF) layer was estimated. TSH, free thyroxine (fT(4)), triiodothyronine (T(3)), thyroid autoantibodies, insulin, glucose, and lipid levels were measured. Subjects receiving T(4) (9.2%) were excluded. RESULTS: SF and SF/PF ratio were inversely correlated with fT(4) levels (r=-0.169, P=0.023, r=-0.193, P=0.009 respectively). In multivariate analysis, fT(4) was a predictor of SF and SF/PF, independently of age, sex, and smoking. SF correlated with TSH levels (r=0.149, P=0.037). PF and SF were positively associated with T(3) levels (r=0.245, P=0.004 and r=0.189, P=0.019 respectively). T(3) levels were positively associated with BMI (r=0.257, P=0.0004), waist perimeter (r=0.324, P<0.0001), and waist-to-hip ratio (WHR; r=0.363, P<0.0001). The T(3)/fT(4) ratio was positively correlated with SF (r=0.182, P=0.028), WHR (r=0.267, P=0.0003), and BMI (r=0.146, P=0.043). CONCLUSIONS: Increasing SF accumulation as assessed by US is associated with lower fT(4) and higher TSH levels among euthyroid slightly overweight individuals. These associations indicate that subtle variation in thyroid function may participate in regional adiposity.

Stauffer's syndrome as a prominent manifestation of renal cancer: a case report.

BACKGROUND: Renal cell carcinoma is associated with a wide spectrum of para-neoplastic syndromes, which may be precursors of primary or recurrent disease. Non-metastatic hepatic dysfunction in patients suffering from renal cell carcinoma is known as Stauffer's syndrome. It is associated with the production of cytokines by the tumour, and several biochemical abnormalities, including elevated serum alkaline phosphatase. CASE PRESENTATION: We describe a 36-year-old woman presenting with various non-specific, systemic disease manifestations, and elevated liver enzymes due to cholestasis as the main laboratory abnormality. Imaging studies showed a solid mass in the left kidney, which, after surgical excision, was identified as renal cell carcinoma. No metastasis was found. CONCLUSION: Stauffer syndrome may precede other manifestations of renal cell carcinoma. In case of unexplained abnormal liver function, particularly in presence of systemic symptoms, underlying renal cell carcinoma should be excluded by focused investigations.

Differential associations of renal function with coronary and peripheral atherosclerosis.

BACKGROUND: The aim of this study was to examine the impact of renal dysfunction on both coronary and peripheral atherosclerosis in patients with coronary artery disease (CAD) without severe renal impairment. METHODS: One hundred and eighty-seven consecutive patients referred for elective coronary angiography were enrolled. Mean IMT and the presence of plaques were measured in the carotid and femoral arteries prior to angiography as markers of subclinical peripheral atherosclerosis. The severity of CAD was evaluated by the Gensini score. Glomerular filtration rate (GFR) was estimated by the MDRD formula. RESULTS: Significant CAD (>50% stenosis) was identified in 139 patients. GFR independently correlated with the presence and severity of CAD with incremental value over that of IMT. Renal function was significantly but not independently correlated with carotid IMT in CAD patients. Femoral IMT and the presence of plaques did not show any significant correlations with GFR in patients with or without CAD. CONCLUSIONS: Renal function is an important predictor of the presence and severity of angiographic CAD in patients without severe renal impairment with incremental value over traditional risk factors for CAD and IMT. The contrasting weak or no associations of GFR with IMT and the presence of plaques suggest that renal dysfunction may exert differential effects on the development of coronary and peripheral atherosclerosis.

Association of thyroid function with arterial pressure in normotensive and hypertensive euthyroid individuals: A cross-sectional study.

BACKGROUND: Overt hypothyroidism has been associated with arterial hypertension and increased arterial stiffness. Results in euthyroid individuals have been conflicting. We investigated associations of thyroid function with systolic (SAP) and diastolic (DAP) arterial pressure in euthyroid subjects. METHODS: 311 euthyroid individuals (185 women, mean age 43.9 +/- 9) without a history of diabetes attending a preventive medicine program were examined. Subjects receiving thyroxine (10.6%) were excluded; 19.3% had hypertension, 43% had a family history for hypertension. TSH, fT4, thyroid autoantibodies, insulin, glucose were measured. The "fT4.TSH product", which has been suggested as a T4 resistance-index, was calculated. RESULTS: TSH range was 0.1-8, median 1.4 mU/L, fT4 range was 11.5-25.2 pmol/L, median 17.4. TSH and the "fT4.TSH product" were positively associated with DAP (p < 0.03, for both associations). In the subgroup of individuals with TSH levels 0.36-2.5 mU/L, both TSH and the "fT4.TSH product" were positively correlated with SAP (r = +0.133 p = 0.044, r = +0.152 p = 0.026) and DAP (r = +0.243 p < 0.001, r = +0.252 p < 0.001 respectively); in multivariate analysis the "fT4.TSH product" was a significant predictor of DAP independently of HOMA-IR and BMI (p < 0.001). Similar associations were found when only the non-hypertensive subjects were analysed (p = 0.004). Hypertensive patients had higher TSH levels (p = 0.02) and belonged more frequently to the subgroup with TSH > 2 mU/L (35.3% vs 21.3%, p = 0.045). CONCLUSION: In euthyroid individuals the association of thyroid function with diastolic arterial pressure remains significant even when a stricter "normal range" for TSH levels is considered. The "freeT4.TSH" product appears to be an even stronger predictor of DAP, independently of HOMA insulin resistance index and obesity.

The association between glycemia and endothelial function in nondiabetic individuals: the importance of body weight.

The aim of this study was to examine the association between glycemia and markers of early atherosclerosis in healthy nondiabetic individuals. In 309 individuals without diabetes or symptomatic cardiovascular disease, we assessed long-term glycemia by glycosylated hemoglobin (HbA1c) and endothelial function by flow-mediated dilatation (FMD) in the brachial artery. HbA1c was negatively associated with FMD (r = -0.162, P = 0.004). Multivariate linear regression analysis after adjusting for common risk factors of cardiovascular disease showed that BMI was an effect modifier of the association between HbA1c and FMD (P = 0.034 for the HbA1c x BMI interaction). We stratified the FMD outcome data into two groups separated by the median BMI (group 1: BMI < or = 26.1 kg/m(2) and group 2: BMI > 26.1 kg/m(2)). In the lower BMI group, HbA1c was an independent predictor of FMD even when adjusted for confounding factors associated with impaired glucose metabolism (r = -0.215, P = 0.009), but in the higher BMI group HbA1c was not associated with FMD (r = -0.051, P = 0.5). In a nondiabetic population, long-term glycemia was associated with endothelial dysfunction only in lean individuals. In the overweight individuals, this association was not apparent, possibly because some of the mechanisms that mediate the effect of glycemia on vascular function are shared by obesity.

Acute smoking induces endothelial dysfunction in healthy smokers. Is this reversible by red wine's antioxidant constituents?

OBJECTIVE: Acute smoking causes endothelial dysfunction through impairment of nitric oxide (NO) production, or increased oxidative stress, but the exact mechanism still needs to be elucidated. In healthy non-smokers acute endothelial dysfunction caused by smoking one cigarette was counterbalanced by red wine's antioxidants. The aim of the present study is to investigate whether red wine's antioxidant substances could counteract the acute endothelial dysfunction induced by acute cigarette smoking in healthy smokers as well. METHODS: Twenty healthy volunteers (12 males) participated in a double-blind, cross-over study, comprised of three study days. All subjects either smoked one cigarette, or smoked and drank 250 ml of red wine, or smoked and drank 250 ml of dealcoholized red wine in each one of the study days. Flow mediated dilatation (FMD) was measured at fast and 30, 60 and 90 minutes after each trial. RESULTS: Smoking one cigarette induced a significant decrease in FMD (p < 0.001), which remained significant 30 (p < 0.001), and 60 (p = 0.003) minutes after the end of smoking. FMD remained statistically unchanged after consumption of either regular red wine, or dealcoholized red wine together with smoking. CONCLUSIONS: The observed endothelial dysfunction following smoking of one cigarette was counterbalanced by consumption of either red wine or dealcoholized red wine in healthy smokers. It is possible that acute endothelial dysfunction caused by smoking could be attributed to increased oxidative stress and red wine's antioxidants counteract these acute effects of smoke on endothelium.