Divergent associations of tissue inhibitors of metalloproteinases-1 and -2 with the prothrombotic/fibrinolytic state.
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Adult↗
Biomedical subjects
Christodoulos Stefanadis
Publications and source records attributed to Christodoulos Stefanadis.
Beat by beat variations.
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Calcium Gluconate↗
Metabolic syndrome prevalence and characteristics in Greek adults with familial combined hyperlipidemia.
Familial combined hyperlipidemia (FCH) is closely related with metabolic syndrome (MetSyn), and coronary artery disease (CAD) is positively associated to MetSyn and FCH. In this study, we evaluated the prevalence of MetSyn and its components between patients with FCH and a control group. We also investigated the role of MetSyn and diabetes mellitus (DM) on the incidence of CAD within the FCH group. Our study population consisted of 463 male and 243 female patients with FCH who were not receiving any hypolipidemic treatment, and 1128 men and 1154 women who came from the same geographical region. The prevalence of MetSyn was 42% and 19.8% among FCH subjects and controls, respectively, whereas MetSyn increased with age in both groups. The prevalence of CAD was 15.3% in the FCH group. Moreover, after dividing FCH patients into 3 subgroups, with and without MetSyn and with DM, CAD prevailed at a percentage of 15.2%, 11.1%, and 26.5%, respectively. However, statistically significant differences in the prevalence of CAD were observed only between FCH subjects with DM compared with the other 2 subgroups, even when an adjustment for age, sex, and smoking was conducted. People with FCH and MetSyn differed in several anthropometric, biochemical, and clinical characteristics, compared with the non-MetSyn subgroup of FCH. MetSyn is more prevalent in the FCH than in the control group. Among subjects with FCH, only DM was significantly associated with an increase in the prevalence of CAD in this subgroup compared with FCH individuals with or without MetSyn.
Adult↗
The incremental effect of obstructive sleep apnoea syndrome on arterial stiffness in newly diagnosed essential hypertensive subjects.
OBJECTIVE: Although obstructive sleep apnoea syndrome (OSAS) is accompanied by an increased atherosclerotic cardiovascular disease burden, its relationship with arterial stiffness is not yet well determined. We investigated whether essential hypertensive individuals with OSAS are characterized by increased arterial stiffness. METHODS: Our study population consisted of 46 consecutive patients with newly diagnosed untreated stage I-II essential hypertension suffering from OSAS (35 men, aged 49 +/- 8 years) and 53 hypertensive individuals without OSAS, matched for age, sex, and smoking status. All subjects underwent polysomnography, echocardiography and aortic stiffness evaluation by means of carotid-femoral pulse wave velocity (c-fPWV) measurements. RESULTS: Hypertensive subjects with OSAS [apnoea/hypopnoea index (AHI)>or =5] compared with hypertensive subjects without OSAS (AHI < 5) demonstrated increased levels of body mass index (31.4 +/- 4 versus 29.3 +/- 4 kg/m2, P = 0.015), office systolic/diastolic blood pressure (151/99 versus 145/94 mmHg, respectively, P < 0.05, for both cases) and relative wall thickness (RWT; 0.46 +/- 0.06 versus 0.42 +/- 0.07, P=0.010). Hypertensive subjects with OSAS compared with those without OSAS had significantly increased c-fPWV by 9% (8.56 +/- 0.49 versus 7.85 +/- 0.93 m/s, P=0.001) and this difference remained significant even after adjustment for confounders (P=0.04). In the total study population, c-fPWV was correlated with age (r=0.35, P=0.015), office systolic blood pressure (r=0.30, P=0.007), RWT (r=0.30, P=0.03), logAHI (r=0.389, P=0.0001) and minimum oxygen saturation (r=-0.418, P=0.0001). CONCLUSIONS: OSAS has a significant incremental effect on aortic stiffening in the setting of middle-aged essential hypertensive subjects. This finding suggests that the presence of OSAS in a hypertensive patient accelerates vascular damage, increasing cardiovascular risk.
Adult↗
Association of creatinine clearance and in-hospital mortality in patients with acute coronary syndromes: the GREECS study.
BACKGROUND: The relationship between renal dysfunction and mortality in patients with myocardial infarction (MI) has been extensively investigated, but there are limited data about this relationship in patients presenting with non-ST-segment-elevation MI and unstable angina. Therefore, the aim of the present study was to investigate whether renal insufficiency is an independent predictor for in-hospital mortality among such patients. METHODS AND RESULTS: Two thousand a hundred and seventy-two patients presenting with acute coronary syndrome (ACS) in 6 Greek hospitals were enrolled. Creatinine clearance rates were estimated by the Cockcroft-Gault formula. Five percentage of patients presented with severe renal dysfunction, 27% with moderate dysfunction and the other 68% were normal. Patients with moderate or severe renal dysfunction were older, more likely to be women and more likely to have history of hypertension and diabetes mellitus compared with those with normal renal function. In comparison with patients with normal renal function, those with moderate and severe renal dysfunction were respectively 3- and 12-fold more likely to die. Moreover, moderate and severe renal insufficiency continued to be a prognostic factor for mortality, even after controlling for potential confounders. CONCLUSIONS: Creatinine clearance rate is an important independent predictor of in-hospital mortality, so patients with ACS complicated by renal dysfunction should receive more aggressive medical care.
Aged↗
Evidence that non-lipid cardiovascular risk factors are associated with high prevalence of coronary artery disease in patients with heterozygous familial hypercholesterolemia or familial combined hyperlipidemia.
BACKGROUND: Heterozygous familial hypercholesterolemia (hFH) and familial combined hyperlipidemia (FCH) have been associated with increased risk for coronary artery disease (CAD), but the impact of traditional risk factors to the incidence of CAD in these patients remains unknown. The present study evaluates the contribution of such risk factors to the development of CAD in these two dyslipidemic populations. METHODS: This cross-sectional study enrolled a total 1306 subjects; 600 individuals with hFH (mean age 41+/-13 years, 261 males and 339 females), and 706 individuals with FCH (mean age 49+/-11 years, 463 males and 243 females). Blood samples were collected after 12 hours fasting period, and serum lipids were determined. Multivariate logistic regression models were used to estimate the odds ratios of CAD based on the type of hyperlipidemia, after adjustment for demographic characteristics and risk factors. RESULTS: Subjects with FCH were older (P<0.001), and they had a significantly increased prevalence of hypertension, diabetes and metabolic syndrome (40 vs. 10%, 13 vs. 2% and 41 vs. 6% respectively, all P<0.001) compared to the hFH group. Total cholesterol, LDL-cholesterol, and apolipoprotein B levels were higher (all P<0.001) in hFH subjects. Although in multivariate analysis lipid abnormalities found in hFH were associated with increased risk of CAD (P<0.001) compared with lipid abnormalities of FCH, the overall prevalence of CAD was similar between the two groups (16.7 vs. 15.3%, P=NS). CONCLUSIONS: Despite the high atherogenic potential of altered lipid metabolism found in hFH, the prevalence of CAD is similarly increased in patients with hFH or FCH. This may be related to the clustering of non-lipid cardiovascular risk factors, such as diabetes mellitus, observed in patients with FCH.
Adult↗
The emerging anti-inflammatory role of HDL-cholesterol, illustrated in cardiovascular disease free population; the ATTICA study.
OBJECTIVE: In this work we assessed the relationship between HDL-cholesterol levels and various inflammation markers status in a sample of cardiovascular disease free adult men and women from Greece. METHODS: The ATTICA study is a population-based cohort that has randomly enrolled 1128 men and 1154 women (aged >18 years old), stratified by age-gender, from the greater area of Athens, during 2001-2002. Adherence to Mediterranean diet was assessed through a diet-score that was based on a validated food-frequency questionnaire. In this study we assessed the relationship between HDL-cholesterol levels and inflammation markers (high sensitivity C-reactive protein, interleukin-6, homocysteine and amyloid-a), after taking into account the effect of several confounders. RESULTS: 46% of men and 40% of women had total serum cholesterol levels >200 mg/dl, while 21% of men and 7% of women had HDL-cholesterol levels <35 mg/dl. The mean value for HDL-cholesterol was 53+/-14 mg/dl in females and 44+/-14 mg/dl in males. HDL-cholesterol levels were inversely correlated to the hs-CRP levels (b=-0.028, P=0.001) and homocysteine levels (b=-0.039, P=0.036), after adjustment for sex, age, body mass index, physical activity status, smoking, total cholesterol levels, lipid lower agents, ethanol intake and diabetes mellitus; while no statistical significance was found between HDL-cholesterol levels and interleukin-6 and serum amyloid-a. CONCLUSIONS: In this work we evaluated the inverse relationship between HDL-cholesterol levels and inflammatory markers in a sample adult cardiovascular disease free population. This study among others illustrates the anti-inflammatory emerging role of HDL-cholesterol in reducing cardiovascular risk.
Adult↗
Statins in heart failure. Beyond the lipid lowering effect.
Statins, the most widely prescribed medications in patients with hyperlipidemia and coronary heart disease, have a number of pleiotropic actions beyond cholesterol lowering. They improve endothelial function, they have antioxidant and anti-inflammatory effects, they regulate neovascularization and have immunomodulatory activities. Experimental evidence suggests that statins may be beneficial in heart failure as they can inhibit myocardial hypertrophy, reduce cardiomyocyte loss by apoptosis, reduce oxidative stress and restore neurohormonal imbalance. Furthermore small randomised clinical trials showed that short term statin administration may improve key pathophysiological aspects of this syndrome. Finally retrospective analyses of large statin trials imply a long term profit on clinical outcome in this group of patients. These results however need to be reviewed with caution as certain studies have demonstrated that low serum cholesterol is associated with worse prognosis in HF and that ubiquinone levels, a micronutrient with antioxidant actions, reduces significantly following statin administration. Large prospective randomised controlled trials are needed to confirm the beneficial effect of statins on cardiovascular outcome in HF patients and further elucidate the contributing mechanisms. Finally the statin dose and the interaction with co-administered drugs need to be studied.
Endothelium, Vascular↗
Large recesses associated with left ventricular noncompaction: an unusual presentation of the disease.
Left ventricular noncompaction (LVNC) represents an arrest of myocardial morphogenesis, resulting in persistence of multiple prominent ventricular trabeculations and deep intertrabecular recesses. We report a case of a 30-year-old patient who was referred to our hospital due to familial history of cardiomyopathy. The patient underwent transthoracic echocardiography, cardiac catheterization and contrast ventriculography and cardiac magnetic resonance imaging. All imaging techniques showed the characteristic pattern of noncompaction together with two unusually large recesses in the inferior wall of myocardium. This unusual form of LVNC may have an impact on the clinical course of the disease and may require anticoagulation therapy.
Adult↗
Real-time three-dimensional dobutamine stress echocardiography for coronary artery disease diagnosis: validation with coronary angiography.
OBJECTIVE: To compare real-time three-dimensional echocardiography (RT3DE) with two-dimensional dobutamine stress echocardiography (2DE) for the detection of myocardial ischaemia, with angiographic validation of the results. METHODS: 56 patients (mean (SD) age 64.5 (6.2) years, 38 males), referred for coronary angiography, were examined by 2DE and RT3DE during the same dobutamine stress protocol. RESULTS: All 56 patients completed the stress protocol uneventfully. The mean (SD) acquisition time for the necessary views to evaluate all segments was 26.3 (2.5) s for RT3DE and 58.8 (3.7) s for 2DE (p<0.001). At peak stress, RT3DE had a higher wall-motion score index (1.25 (0.24) by 2DE, 1.30 (0.27) by RT3DE; p = 0.014). The regional wall-motion score for the four apical segments at peak stress was compared; it was 1.35 (0.55) by 2DE and 1.52 (0.69) by RT3DE (p = 0.003). The diagnostic parameters of 2DE versus RT3DE were: sensitivity 73% vs 78%, specificity 93% vs 89% and overall accuracy 86% vs 85%, respectively. In the left anterior descending artery territory, in particular, where RT3DE had higher regional wall-motion scores, it showed a tendency towards higher sensitivity (85% vs 78%), although this difference did not achieve statistical significance. CONCLUSION: RT3DE identifies wall-motion abnormalities more readily in the apical region than 2DE, which may explain the tendency towards higher sensitivity in the left anterior descending artery territory. RT3DE results were validated using angiography as reference and findings indicate diagnostic equivalence to 2DE, with the advantage of considerable shorter acquisition times.
Aged↗
Spontaneous coronary dissection as a cause of acute coronary syndrome: evidence for non-inflammatory underlying mechanisms.
Myocardial infarction in patients without atherosclerotic coronary artery disease is a rare syndrome. Several pathophysiologic mechanisms have been proposed, such as spontaneous coronary dissection, intramural hematoma, coronary vasospasm and thrombosis. Diagnosis can be confirmed by coronary angiography and intravascular ultrasound, while the presence of an inflammatory process within the coronary artery wall can be detected from local heat production by intracoronary thermography. We present two women with acute coronary syndrome, due to a limited spontaneous coronary dissection and an intramural hematoma detected by coronary angiography and intravascular ultrasound.
Acute Disease↗
Unfavourable endothelial and inflammatory state in erectile dysfunction patients with or without coronary artery disease.
AIMS: Erectile dysfunction (ED) confers an independent cardiovascular risk. We investigated the role of low-grade inflammation and endothelial dysfunction in ED patients with or without coronary artery disease (CAD). METHODS AND RESULTS: We evaluated 141 men (age 58.8 years) for ED and CAD through a rigourous investigation (including coronary angiography to reveal occult CAD). Blood levels of inflammatory (hsCRP, IL-6, IL-1beta, and TNF-alpha) and endothelial-prothrombotic markers/mediators (vWF, tPA, PAI-1, and fibrinogen) were significantly increased in ED patients and correlated negatively with sexual performance. ED was associated with higher levels of these substances (except for IL-6) on top of CAD alone. For most substances, the unfavourable impact of ED alone was not significantly different than the impact of CAD alone. In multivariable models, these markers/mediators predicted independently ED presence. In our population, the negative predictive value of the combination of fibrinogen <225 mg/dL with IL-6 <1.24 pg/mL for excluding ED was 91.7% (95% CI: 61.5-99.8). CONCLUSION: ED is associated with increased inflammatory and endothelial-prothrombotic activation in men with or without CAD. ED confers an incremental unfavourable impact on the circulating levels of these markers/mediators when combined with CAD. These findings have implications for increased cardiovascular risk in ED patients.
Biomarkers↗
Nitric oxide-releasing aspirin: will it say NO to atherothrombosis?
Aspirin is a powerful anti-platelet drug widely used in patients with coronary atherosclerosis, but its side effects and especially its toxicity for gastrointestinal tract limit its usefulness in specific groups of patients. A new category of agents, nitric oxide-releasing aspirins (such as NCX-4016), seems to provide an alternative solution. Although this drug is still at phase II clinical trials, it has provided promising results until now. When administered in vivo, it is separated into an aspirin moiety and an NO-donating complex, providing both the antithrombotic effect of aspirin and the gastroprotective effect of NO. Additionally, it increases NO bioavailability as a vascular level, and it may have the antiatherogenic properties of endogenously produced NO. Finally, recent evidence suggests that it may also improve functional aspects of vein grafts used in CABG, with possible benefit on graft patency. However, the outcome of the large ongoing trials is needed before any conclusion is made about the role of NO-releasing aspirins in cardiovascular disease.
Aspirin↗
Alterations of pressure waveforms along the coronary arteries and the effect of microcirculatory vasodilation.
OBJECTIVES: We sought to investigate the differences of pressure waveforms at a distal point of an epicardial coronary artery comparatively to the ostium and to assess the effect of microcirculatory vasodilation on them. BACKGROUND: Pressure waveforms in the systematic circulation and their alterations along the aorta due to wave reflections from the periphery have been extensively studied. However, similar data regarding intracoronary pressure waveforms and the effects of coronary microcirculation on them are limited. METHODS: In 18 patients who underwent diagnostic coronary angiogram or percutaneous coronary intervention in the left circumflex or the right coronary artery, we studied pressure waveforms recorded by a high-fidelity pressure wire, which was advanced to the ostium and to a distal site of the free of significant lesions left anterior descending coronary artery. Pressure recording was performed both at rest and at hyperemia induced by intravenous infusion of adenosine. Analysis of pressure waveforms at the frequency domain was performed with Fast Fourier Transform. RESULTS: At baseline conditions, distal pressure waveforms were characterized by higher pulsatility, higher presystolic wave and higher amplitude of the 11th to the 15th harmonics. Hyperemia increased the pulsatility, compressed the notch and decreased the amplitude of higher than the 10th harmonics of distal waveforms. CONCLUSIONS: This study identifies differences of pressure waveforms between proximal and distal sites of free of significant lesions coronary arteries, which are affected by the status of coronary microcirculation and may therefore facilitate assessment of microvascular disease.
Adenosine↗
Effects of atorvastatin and vitamin C on forearm hyperaemic blood flow, asymmentrical dimethylarginine levels and the inflammatory process in patients with type 2 diabetes mellitus.
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Anti-Inflammatory Agents↗
Prevalence of self-reported hypertension and its relation to dietary habits, in adults; a nutrition & health survey in Greece.
BACKGROUND: Hypertension leads to many degenerative diseases, the most common being cardiovascular in origin. This study has been designed to estimate the prevalence of self-reported hypertension in a random nationwide sample of adult Greek population, while focus was set to the assessment of participants' nutritional habits in relation to their hypertension status. METHODS: A random-digit dialed telephone survey. Based on a multistage, stratified sampling, 5003 adults (18 - 74 yr) participated (men: 48.8%, women: 51.2%). All participants were interviewed via telephone by trained personnel who used a standard questionnaire. The questionnaire included demographic and socioeconomic characteristics, medical history, lifestyle habits and nutritional assessment. RESULTS: The prevalence of self-reported hypertension was 13.3% in men and 17.7% in women (P < 0.001). Furthermore, women reported higher values of systolic blood pressure (180 +/- 27 mmHg) than men (169 +/- 24 mmHg). Positive relationships were found between hypertension status and the prevalence of the rest investigated health conditions (i.e. hypercholesterolaemia, diabetes mellitus, renal failure and obesity). Nutritional assessment showed that consumption of fish, fruits and juices, cereals, and low fat milk and yogurt was significantly higher among hypertensive subjects while the opposite was observed for food items as red meat, pork, egg, pasta and rice, full fat dairy products and desserts. CONCLUSION: Hypertension seems to be a serious public health problem in Greece. It is encouraging that hypertensives may have started adopting some more healthy nutritional behaviour compared to normotensive ones. However, they can gain significant benefits regarding to blood pressure control, if they increase the level of compliance with dietary recommendations.
Adolescent↗
The implication of obesity on total antioxidant capacity in apparently healthy men and women: the ATTICA study.
BACKGROUND AND AIM: We evaluated the association of obesity with serum total antioxidant capacity (TAC), in a population-based sample of 3042 adults. METHODS AND RESULTS: During 2001-2002 we randomly enrolled 1514 men (18-87 years old) and 1528 women (18-89 years old), from the Attica area in Greece into the study, and the sample was stratified by the age-sex distribution of the region (census 2001). Among several variables we also measured serum TAC and weight, height, waist and hip circumferences. Waist circumference greater than 102 cm for men and 88 cm for women was considered an indicator of central fat. METHODS AND RESULTS: Mean waist circumference was 98+/-13 cm in men and 84+/-22 cm in women (P<0.001), while mean hip circumference was 106+/-28 cm in men and 103+/-13 cm in women (P<0.001). Central fat prevailed in 53% of men and 45% of women (P<0.001). Male participants with central fat exhibited 5% lower TAC concentrations compared to leaner individuals (214+/-35 vs. 226+/-33 micromol/L, P=0.04) and female participants with central fat exhibited 7% lower TAC concentrations (256+/-38 vs. 239+/-27 micromol/L, P=0.03). Similarly, obese or overweight male participants had 6% lower TAC concentrations compared to normal weight (217+/-33 vs. 234+/-39 micromol/L, P=0.03) and female obese or overweight participants had 10% lower TAC concentrations (226+/-32 vs. 250+/-30 micromol/L, P=0.02) compared to the others. CONCLUSIONS: Our results suggest an inverse relationship between body fat, central adiposity and antioxidant capacity, irrespective of age and various other potential confounders, namely smoking, physical activity, dietary habits, blood pressure, glucose levels, and lipid concentrations.
Abdominal Fat↗
Arrhythmogenic right ventricular cardiomyopathy caused by deletions in plakophilin-2 and plakoglobin (Naxos disease) in families from Greece and Cyprus: genotype-phenotype relations, diagnostic features and prognosis.
AIMS: To evaluate clinical disease expression, non-invasive diagnosis, and prognosis in families with dominant vs. recessive arrhythmogenic right ventricular cardiomyopathy (ARVC) due to mutations in related desmosomal proteins plakophilin-2 (PKP2) and plakoglobin (JUP), respectively. METHODS AND RESULTS: One hundred and eighty-seven individuals belonging to ARVC families, four with dominant PKP2 mutations and 12 with recessive JUP mutation underwent serial non-invasive cardiac assessment. Survival and arrhythmic events were evaluated prospectively up to 21 years (median 8.5 years). Sixteen of 22 PKP2 carriers and all 26 homozygous JUP carriers fulfilled the diagnostic criteria for ARVC, the youngest by the age of 13 years. Clinical disease expression did not differ significantly between PKP2 and JUP carriers. T-wave inversion in leads V1-V3, right ventricular wall motion abnormalities, and frequent ventricular extrasystoles were the most sensitive/specific markers for identification of mutation carriers. QRS dispersion > or =40 ms was an independent predictor of syncope but not of sudden death. CONCLUSION: Mutations in PKP2 and JUP express similar cardiac phenotype. Non-invasive family screening may largely be based on T-wave inversion, right ventricular wall motion abnormalities, and frequent ventricular extrasystoles to identify mutation carriers.
Adolescent↗