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Publications and source records attributed to C Pitsavos.
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Familial hypercholesterolaemia is a genetic disorder characterised by high low-density lipoprotein (LDL) cholesterol concentrations, which frequently gives rise to premature coronary artery disease (CAD). The clinical expression of familial hypercholesterolaemia is highly variable even in patients carrying the same LDL receptor gene mutation. This variability may be due to environmental and other genetic factors. Apolipoprotein E (Apo-E) has been extensively studied for its effects on the phenotype of familial hypercholesterolaemia. In this study we examined the influence of Apo-E genotype on lipid parameters and the incidence of CAD in 93 Greek patients with familial hypercholesterolaemia. Apo-E E2, E3 and E4 allele frequencies were 0.06, 0.86 and 0.09 respectively. The levels of total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, apolipoproteins A and B and lipoprotein alpha did not differ significantly among carriers and non-carriers of the E4 allele. The prevalence of CAD and hypertension did not differ either. Our results suggest that the E4 allele is not associated with lipid levels or with the prevalence of CAD among familial hypercholesterolaemia patients of the Greek population.
AIMS: To identify the threshold of alcohol consumption above which the balance of risk and benefit becomes adverse in diabetic subjects. METHODS: We studied demographic, lifestyle, dietary and clinical information in 216 hospitalized diabetic patients (171 men, 63 +/- 9 years old, 45 women, 67 +/- 5 years old) with a first event of an acute coronary syndrome (ACS) and 196 frequency matched (age-sex) diabetic controls, without any clinical evidence of coronary heart disease. Alcohol consumption was quantified and a measure for the comparisons was predetermined to be a wine glass (100 ml of wine, 12 g of ethanol) and its alcohol equivalents. RESULTS: Alcohol consumption was associated with an age-adjusted J-shape relationship with total cholesterol, blood pressure and smoking (all P < 0.001). A J-shape association was also found between alcohol intake and the risk of ACS (OR = 2.54-2.43 x (alcohol intake) + 0.80 x (alcohol intake)2, R2 = 0.96, P < 0.001), adjusted for several risk factors and interactions between alcohol intake and smoking status, job and familial stress, and low income. In particular, low alcohol consumption (< 12 g/day) was associated with a 47% (OR = 0.53, 95% CI 0.28-0.97) reduction of the prevalence of ACS, while a higher intake (12-24 and > 24 g/day) increased the prevalence by 2.7-fold (OR = 2.72, 95% CI 1.39-5.38) and 5.4-fold (OR = 5.44, 95% CI 1.21-24.55), respectively. CONCLUSIONS: Alcohol intake is a significant predictor of coronary events. Low-to-moderate intake seems to be associated with a reduction in the prevalence of ACS in diabetes, whereas higher consumption is associated with an increase in lipids and blood pressure levels, and also the risk of developing ACS.
AIMS: Individuals with Type 2 diabetes are at high risk for coronary heart disease, and may benefit from aggressive lifestyle modification. We evaluated the prevalence of Type 2 diabetes, in a Greek adult population, in relation to physical activity and dietary habits. METHODS: From May 2001 to December 2002, we randomly enrolled 1514 men and 1528 women, with no evidence of cardiovascular or any other chronic disease. The sampling was stratified by the age and gender distribution of the general population in the greater area of Athens (census 2001). Diabetes was defined according to the established American Diabetes Association criteria. Dietary habits were assessed through a validated food frequency questionnaire and a diet score was developed, in which higher values suggest greater adherence to the Mediterranean diet. Weekly energy expenditure was assessed by considering frequency, duration and intensity of sports-related physical activity during a usual week. RESULTS: After age adjustment for the Greek adult population (2001 census), the projected prevalence of Type 2 diabetes was 7.6% in men and 5.9% in women. A significant proportion of diabetic subjects (24% of men and 30% of women) were unaware of their condition. Moreover, a 10-unit increase in the diet score was associated with 21% lower odds of diabetes (P < 0.05), while individuals taking light physical activity were at 35% lower odds ratio of diabetes compared with sedentary individuals (P < 0.05). CONCLUSIONS: Diabetes mellitus is common in our population, with approximately 1 in 5 individuals with Type 2 diabetes being unaware of their condition. The lifestyle approach described here may contribute significantly to the reduction in the prevalence of diabetes, at a population level.
OBJECTIVE: To investigate the effects of short term atorvastatin treatment on forearm vasodilatory response to reactive hyperaemia (RH%) and on components of the thrombosis-fibrinolysis system (antithrombin III, proteins and S, factors V and VII, von Willebrand factor, tissue plasminogen activator (tPA), and plasminogen activator inhibitor (PAI-1)) in patients with heart failure. PATIENTS AND METHODS: 35 patients with heart failure were enrolled in this study; 17 patients received atorvastatin 10 mg/day and 18 patients received no statin for four weeks. Forearm blood flow (FBF) was measured by venous occlusion strain gauge plethysmography. RH% and forearm vasodilatory response to nitrate were defined as the percentage change of FBF from rest to the maximum flow during reactive hyperaemia and after nitrate administration, respectively. Plasma concentrations of antithrombin III, protein C, protein S, factor V, factor VII, von Willebrand factor, tPA, and PAI-1 were determined before and after treatment. RESULTS: Maximum hyperaemic FBF remained unchanged in both groups. Baseline FBF was slightly but not significantly decreased in the atorvastatin treated group. RH% was significantly increased only in the atorvastatin treated group, from mean (SD) 42.44 (18.9)% to 83.7 (36.1)% (p < 0.01). Plasma concentrations of antithrombin III (from mean (SD) 81.7 (11.37)% to 73.5 (13.8)%), protein C (from mean (SD) 88.3 (26.9)% to 63.9 (25.0)%), factor V (from mean (SD) 126.2 (33.4)% to 94.9 (29.8)%), tPA (from median (25th-75th percentile) 11.68 (8.60-20.95) ng/ml to 10.30 (8.65-15.12) ng/ml), and PAI-1 (from median (25th-75th percentile) 3.10 (2.15-4.40) IU/l to 1.90 (0.75-3.0) IU/l) were significantly decreased in the atorvastatin treated group (p < 0.05) but not in the control group. Plasma concentrations of von Willebrand factor, factor VII, and protein S remained unaffected in both groups. CONCLUSION: Atorvastatin did not change the maximum hyperaemic flow, although it decreased plasma concentrations of antithrombin III, protein C, factor V, tPA, and PAI-1 in patients with heart failure. Therefore, short term treatment with atorvastatin may affect the expression of both endothelium and liver derived components of the thrombosis-fibrinolysis system in patients with heart failure.
Left ventricular hypertrophy (LVH) is a dominant characteristic of cardiovascular mortality. We investigated the interaction between physical activity and LVH on stroke mortality, based on a 40-year follow-up of the Corfu cohort from the Seven Countries Study. The population studied consisted of 529 rural men (40-59 years old) enrolled in the Study at 1961. LVH was electrographically confirmed according to Minnesota coding. Physical activity levels were assessed by self-reports of habitual, occupational and leisure-time activities. Cox proportional hazard models were used to evaluate exercise levels with respect to stroke mortality in people with and without LVH. During the follow-up, 461 (87%) died, and 74 (16%) of these deaths were due to stroke. LVH was present in 40 (7.5%) men. A total of 362 (68%) men were defined as physically active. Physical activity was associated with a lower risk of stroke (hazard ratio=0.65, P<0.05). On the other hand, LVH had 5.8-fold the risk of stroke (P<0.001) among sedentary and 4.5-fold the risk (P<0.001) among physically active men, after controlling for several potential confounders. However, moderate physical activity decreased the risk of stroke by 49% in men with LVH as compared to sedentary without LVH (hazard ratio=0.51, P<0.01), while hard exercise did not confer any significant reduction in stroke risk. We revealed the benefits from moderate physical activity on stroke mortality among men with LVH. Physicians and other health-care professionals should encourage patients with LVH to adopt a physically active lifestyle.
BACKGROUND: Familial hypercholesterolaemia (FH) is caused by mutations in the low-density lipoprotein receptor gene and the gene encoding apolipoprotein B-100, affecting one in 500 individuals. METHODS: One hundred and eighty-three Greek FH patients were screened for mutations on the LDLR and ApoB genes. RESULTS: We identified mutations in 67 probands and 11 relatives. Sixteen mutations located in eight different exons and the promoter of the LDLR were discovered. Among them 10 were missense mutations (C6W, S265R, A370T, Q363P, D365E, V408M, A410T, A517T, G528D, G571E), two were nonsense mutations (Q363X and C660X), three were splice defects (2140 + 5G-->A and 2140 + 9C-->T, 1706 - 10G-->A), and one was a nucleotide substitution (- 45delT) on the promoter. None of the subjects carried any apoB mutation. The detection rate of mutations in this study was 43%. From the above mutations, A410T, A519T and the splice site defects 2140 + 9C-->T were detected for the first time in the Greek population. Among them V408M, G528D, C6W and S265R account for 73% of heterozygous FH probands. V408M mutation is more common in Central West, while C6W is more common in Central East. Separating the patients into two groups (receptor defective and receptor negative) we found that the receptor negative group had higher levels of total cholesterol, low-density lipoprotein cholesterol and higher prevalence of tendon xanthomas compared with the receptor-defective group. DISCUSSION: The homogenous molecular basis of familial hypercholesterolaemia in Greece facilitates the application of a DNA diagnostic strategy based on the origin of the patient. The early mutation analysis would add valuable information on the severity of the disease.
In a patient with familial hypercholesterolemia (FH), we have identified a new mutation (-45delT) in repeat 3 of the low-density lipoprotein receptor (LDLR) gene promoter. Analysis of a neutral polymorphism in the LDLR mRNA from the patient's white blood cells showed that the expression of one allele was significantly reduced, and cells have only 24% of LDLR activity by binding and uptake of DiI-LDL. Transient transfection studies using a luciferase gene reporter revealed that the -45delT mutation considerably reduces the transcriptional activity of the LDLR promoter and strongly suggest that the mutation is the cause of the FH phenotype.
This study was designed to test the hypothesis that plasma concentrations of matrix metallo-proteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), two enzymes that share similar substrate specificity (collagen type IV and V), possibly related to vascular remodelling, are altered in essential hypertension. The second aim of the study was to assess whether chronic antihypertensive treatment with the calcium channel blocker amlodipine would normalize these alterations. To test this hypothesis, we measured plasma concentrations of active MMP-2 and MMP-9 in 42 patients with never-treated essential hypertension and in 25 normotensive control subjects. Measurements were repeated after 6 months of treatment with the calcium channel blocker amlodipine. Baseline values of MMP-2 and MMP-9 were decreased (P=0.01 and 0.002, respectively) in hypertensive patients compared with normotensives. Hypertensive patients with systemic vascular resistances <1440 dyn s/cm(5) exhibited higher values of MMP-2 (P=0.005) and MMP-9 (P=0.001) than hypertensive patients with systemic vascular resistances >1440 dyn s/cm(5). Treated patients attained a nonsignificant increase in MMP-2 plasma concentrations, but a significant increase in MMP-9 plasma concentrations (P=0.01) compared to respective values before treatment. In conclusion, these findings suggest that plasma concentrations of active MMP-2 and MMP-9, mainly related to vascular extracellular matrix metabolism, are depressed in patients with essential hypertension. A 6 month treatment with amlodipine can normalize MMP-9 but not MMP-2 plasma concentrations. The hypothesis that antihypertensive treatment may modulate collagen metabolism remains to be determined by further studies.
We sought in this study to examine the relationship between microalbuminuria and cardiac geometry since a slight increased urinary albumin excretion (UAE) and increased left ventricular (LV) mass have both been identified as predictors of cardiovascular events in hypertensive subjects. For this purpose, microalbuminuria was determined in three non-consecutive 24-h urine samples as UAE of 20-200 mg/24 h in a group of 249 untreated hypertensive subjects. Echocardiographic classification of patients into LV geometric patterns was based on relative wall thickness values and on gender-specific values for LV mass index (LVMI). The group of patients with microalbuminuria (n = 119) was matched for age, sex, body mass index, smoking status and plasma cholesterol level with the group of patients without microalbuminuria (n = 130). Subjects with microalbuminuria had significantly increased LVMI (111 vs 90 g/m(2), P < 0.0001), relative wall thickness (0.46 vs 0.41, P < 0.001) and office systolic and diastolic blood pressure (161 vs 148 and 101 vs 97 mmHg, respectively, P < 0.005). For the pooled population, UAE was positively correlated to LVMI (r = 0.46, P < 0.001) and relative wall thickness (r = 0.47, P < 0.001). In the entire population, normal LV geometry, concentric LV remodelling, eccentric and concentric LV hypertrophy was found in 34%, 33%, 12% and 21%, respectively. The prevalence of normal LV geometry was significantly higher in normoalbuminuric compared with microalbumnuric subjects (55 vs 14%, P < 0.001) while the prevalence of concentric LV hypertrophy was significantly higher in microalbuminuric compared with normoalbuminuric subjects (32 vs 5%, P < 0.0001). Multiple regression analysis revealed that concentric LV hypertrophy was significantly associated with increased values of UAE and mean arterial pressure. In conclusion, the higher prevalence of unfavourable LV geometric patterns in hypertensive subjects with microalbuminuria compared with those without microalbuminura, may account for the worse cardiovascular outcomes associated with the presence of an increased UAE in hypertensive subjects.
The World Health Organization reports that the number of hypertensives, worldwide, is estimated to be 600 million people. In addition a considerable proportion of hypertensive subjects remains untreated or uncontrolled. In this work we investigated the combined effect of physical activity and Mediterranean diet on coronary risk, in hypertensives. Thus we randomly selected, from all Greek regions, 848 hospitalised patients (695 males, 58 +/- 10 years old and 153 females, 65 +/- 9 years old) with a first event of coronary heart disease (CHD) and 1078 paired, by sex, age, region controls, without any suspicions for CHD. Physically active were those who reported non-occupational physical activity more than once per week. Subjects 'closer' to the Mediterranean diet were assessed through a special nutrient questionnaire. A total of 418 (49%) of the patients and 303 (28%) of the controls were hypertensive. Of these, 115 (27%) patients and 70 (23%) controls were untreated, 148 (35%)-111 (36%) were uncontrolled and 155 (38%)-122 (41%) were controlled (P-value <0.01). One hundred and sixty-two (19%) of the patients and 265 (25%) of the controls (P < 0.01) were 'closer' to the combination of Mediterranean type of diet and physical activity. The analysis showed that the previous combination is related to a 25% reduction of the coronary risk in controlled hypertensive subjects (OR = 0.75, P < 0.01), a 11% reduction in untreated (OR = 0.89, P < 0.05) and 17% reduction (OR = 0.83, P < 0.05) in uncontrolled, after adjusting for age, sex, educational and financial level and the conventional cardiovascular risk factors. Consequently, the adoption of Mediterranean diet by physically active subjects seems to reduce significantly the coronary risk and prevent, approximately, the one-third of acute CHD, in controlled hypertensive subjects.
AIMS: Heat released from atherosclerotic plaques as a result of the local inflammatory process, may be measured in vivo by a thermography catheter. Statins seem to have an antiinflammatory effect which results in plaque stabilization. The aim of this study was to investigate the effect of statins on plaque temperature. METHODS AND RESULTS: The study population included 72 patients: 21 with effort angina, 32 with unstable angina and 19 with acute myocardial infarction. In the study group, 37 patients received statins for more than 4 weeks and 35 were not receiving statins. We measured the temperature difference (deltaT) between the atherosclerotic plaque and the proximal vessel wall (background temperature) using a thermography catheter. The statistical analysis showed that the mean value of deltaT was higher in the untreated group compared to the treated-with-statin, group (0.56+/-0.41 vs 0.29+/-0.33 degrees C, P<0.01). Moreover, a progressive increase in deltaT by type of clinical syndrome was observed in both groups (statin group; effort angina: 0.24+/-0.15, unstable angina: 0.26+/-0.26, acute myocardial infarction: 0.40+/-0.28, vs untreated group; effort angina: 0.41+/-0.26, unstable angina: 0.44+/-0.28, acute myocardial infarction: 0.84+/-0.52, P<0.05). Multivariate analysis showed that treatment with statins was an independent factor in temperature variation, after taking into account the effect of the clinical syndrome (P<0.05). CONCLUSIONS: Patients on statin treatment produce less heat from the culprit coronary lesion than those not treated. Thus, statins seem to have a favourable effect on heat release from atherosclerotic plaques, and whether this effect has an impact on plaque stabilization needs to be investigated in future studies.
OBJECTIVE: To investigate the association between environmental tobacco smoke (ETS) exposure (at least 30 minutes a day) and the risk of developing acute coronary syndromes (ACS). DESIGN AND SETTING: The CARDIO2000 is a case-control study which was conducted in Greece from 2000 to 2001. Cases included 847 individuals with a first event of ACS and 1078 cardiovascular disease-free controls. Cases and controls were frequency matched on age (within three years of age), sex, and region. MAIN OUTCOME MEASURES: ACS was defined as a diagnosis of first acute myocardial infarction or unstable angina. Main independent variable: Exposure to ETS was measured by self report as follows: after the second day of hospitalisation for the cases, and at the entry for the controls, participants were asked whether they were currently exposed to tobacco smoke from other people (home and/or work) for more than 30 minutes a day. The responses were categorised into three levels: no exposure, occasional exposure (< 3 times per week), and regular exposure. In addition participants were asked how many years they had been exposed. Because these were self reported assessments and prone to bias, the results were compared to reports obtained from subjects' relatives or friends, using the Kendal's tau coefficient that showed high agreement. RESULTS: 731 (86%) of the patients and 605 (56%) of the controls reported current exposure of 30 minutes per day or more to ETS. Among current non-smokers, cases were 47% more likely to report regular exposure to ETS (odds ratio (OR) 1.47, 95% confidence interval (CI) 1.26 to 1.80) compared to controls. Exposure to ETS at work was associated with a greater risk of ACS compared to home exposure (+97% v +33%). The risk of ACS was also raised in active smokers (OR 2.83, 95% CI 2.07 to 3.31) regularly exposed to ETS. CONCLUSIONS: This study supports the hypothesis that exposure to ETS increases the risk of developing ACS. The consistency of these findings with the existing totality of evidence presented in the literature supports the role of ETS in the aetiology of ACS.
Percutaneous coronary transluminal angioplasty (PTCA) may release inflammatory mediators such as chemokines. Monocyte chemoattractant protein-1 (MCP-1) and eotaxin (EOX) are monocyte- and eosinophil-specific chemokines involved in the inflammation and pathogenesis of coronary atherosclerosis. A total of 28 patients undergoing elective PTCA, 20 coronary artery disease (CAD) patients undergoing coronary angiography and 28 healthy controls were studied. In PTCA patients before the procedure, MCP-1 plasma levels (441+/-64 pg/ml) were similar to those of CAD patients (430+/-24 pg/ml), and significantly higher compared with controls (145+/-17 pg/ml, P<0.01). MCP-1 rose significantly after 3 and 6 months following PTCA (696+/-89 and 876+/-86 pg/ml, respectively, P<0.01 vs. before PTCA). EOX plasma levels (155+/-14 pg/ml) were similar to those of CAD patients (157+/-14 pg/ml), but significantly higher compared with controls (83.2+/-10 pg/ml, P<0.05). EOX rose significantly 24 h (273+/-41 pg/ml, P<0.05) but not 3 months after PTCA (160+/-20 and 158+/-19 pg/ml, respectively). These findings indicate that chemokine-induced monocyte- and eosinophil-specific chemoattraction is stimulated in patients with coronary artery disease. MCP-1 levels remain significantly elevated for at least 6 months following elective PTCA, suggesting an inflammatory stimulation.
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OBJECTIVE: To identify any possible association between different readily available non-invasive indices and potential malignant ventricular arrhythmias in patients with repaired tetralogy of Fallot. DESIGN: 27 consecutive patients, mean (SD) age 27.3 (11.7) years, were studied 15.7 (6.7) years after corrective surgery for tetralogy of Fallot, using 12 lead ECG, 24 hour Holter recordings, signal averaged ECG, and echocardiography. The following variables were measured: standard QRS duration, filtered QRS duration (fltQRS), low amplitude signal duration, and root mean square voltage of the last 40 ms of the fltQRS (RMS-40), as well as right ventricular systolic pressure, right ventricular ejection fraction, and the ratio of the maximum short axis diameters of the right and left ventricles (RD:LD). RESULTS: All patients had right bundle branch block, with a mean QRS duration of 137.1 (14.9) ms. There were no patients with sustained arrhythmia. Five patients had runs of non-sustained ventricular tachycardia (group A) and the other 22 patients did not (group B). Univariate analysis showed that fltQRS and RD:LD ratio were significantly associated with non-sustained ventricular tachycardia. In addition, a fltQRS >/= 148 ms, low amplitude signal >/= 32.5 ms, RMS-40 </= 23 microV, and RD:LD ratio >/= 1.05 were cut off points with a high sensitivity for detecting patients with non-sustained ventricular tachycardia. CONCLUSIONS: Abnormal signal averaged ECG and echocardiographic variables are associated with potentially malignant ventricular arrhythmias on the Holter recordings in asymptomatic patients with repaired tetralogy of Fallot.
BACKGROUND: In recent decades various lifestyle factors have been associated with the increasing risk of coronary heart disease. The aim of this study is to assess coronary risk, based on established and emerging lifestyle risk factors such as smoking habit, physical activity, alcohol consumption and depression in a Mediterranean population. METHODS: During 2000--2001, 535 male and 126 female patients with a first event of an acute coronary syndrome and 661 controls matched by sex, age and region were entered into the study. Conditional logistic regression analysis estimated the relative risks of developing coronary heart disease under several scenarios. RESULTS: The multivariate analysis showed that stopping smoking is exponentially related to the reduction of coronary risk. By contrast, passive smoking increases the risk from 48% to 112%. Familial smoking habits are related to current smoking status, increasing the coronary risk fourfold. The effect of depression on coronary risk differs according to gender (+15% in males vs. 32% in females), and interacts with retirement, current smoking, physical inactivity, alcohol consumption and social status, increasing the risk from 15% to 189%. A J-shape association was found between alcohol intake and coronary risk Physical inactivity doubles the coronary risk, while long-term physical activity plays a preventive role in the reduction of coronary risk, even in the elderly. CONCLUSION: Analysis of the data showed that the cluster of established and emerging lifestyle factors poses its particular role for further investigation in the aetiology of coronary heart disease.
OBJECTIVE: The aim of this study is to evaluate the effect of recent depressive episodes on coronary risk, taking into account the presence of several cardiovascular risk factors and various lifestyles, and social conditions that aggregate in the Greek population. METHODS AND RESULTS: CARDIO2000 is a matched case-control study consisting of 750 patients with a first event of acute coronary syndrome and 778 cardiovascular disease-free hospitalized subjects, randomly and stratified selected from several Greek regions. Assessment of depressive symptoms, during the past month, was based on the CES-D Scale (Radloff S, 1977). 158 (21%) coronary patients and 74 (9%) controls had short-term depressive symptoms (P<0.001). A recent depressive episode increases coronary risk by 12%, after adjusting for several confounders, while the previous outcome seems to differ significantly between sexes (OR-men = 1.09 vs. OR-women = 1.19, P<0.01). The effect of the interaction between depression and various components of social class (education, occupation, income) increases the coronary risk from 55% to 132%, while the interaction with marital status increases the previous risk by 167%, in divorced/widowed men, and by 123%, in women. Also, significant additive effects were observed between depression and smoking (25% increased coronary risk per pack-year), alcohol consumption (+97%), physical inactivity (+137%) and obesity (+127%). CONCLUSION: This study showed the moderate effect of recent depression on the risk of developing non-fatal acute coronary syndromes in the investigated population. Also, sex differences and the additional effect of the interactions between short-term depressive episodes and several emerging or established cardiovascular risk factors occurred.