Contribution of plasma matrix metalloproteinases to development of left ventricular hypertrophy and diastolic dysfunction in hypertensive subjects

Matrix metalloproteinases (MMPs) are involved in the regulation of the extracellular matrix (ECM) of the myocardium and thus the pathogenesis of vascular and cardiac hypertrophy. In this study, we investigated contribution of plasma matrix metalloproteinases to development of left ventricular hypertrophy (LVH) and diastolic dysfunction in hypertensive subjects. Hypertensive patients with (n = 27) and without LVH (n = 23) were included. All participants underwent a complete transthoracic echocardiographic examination, including recordings of the mitral annular early, late, systolic and diastolic velocities by Doppler imaging. Plasma concentrations of MMP-3 and MMP-9 were determined by the one-step sandwich enzyme immunoassay method. Plasma MMP-3 and MMP-9 concentrations were significantly higher in patients with LVH than those without LVH (2.4 +/- 1.2 vs 1.5 +/- 0.7 ng/ml, p = 0.006 and 5.2 +/- 2.8 vs 3.3 +/- 1.7 ng/ml, p = 0.003, respectively). MMP-3 and MMP-9 levels were also correlated with left ventricular posterior wall thickness and Doppler indices of diastolic dysfunction. Our findings have suggested that increased MMP levels may contribute to LVH and left ventricular diastolic dysfunction. Therefore, treatment of hypertension with MMP lowering drugs, such as angiotensin converting enzyme inhibitors and angiotensin receptor blockers, may have favorable effects on LVH and left ventricular diastolic dysfunction.     

Impairment of flow-mediated vasodilatation of brachial artery in patients with Cushing's Syndrome

Background Cushing’s Syndrome (CS) is associated with excess and premature cardiovascular disease. Endothelial dysfunction is the initiating event in the development of atherosclerosis. Endothelial function is assessed by flow-mediated dilatation (FMD) of brachial artery. The aim of this study was to assess FMD in patients with CS. Methods We prospectively evaluated 22 patients with CS (12 women, 10 men; aged 42 ± 11 years, serum cortisol 28.2 ± 14 μg/dl, 24-h urinary free cortisol (UFC) 269 ± 92 μg/day), and 23 control subjects (13 women, 10 men; aged 43 ± 10 years, serum cortisol 14 ± 4 μg/dl, 24 h cortisol 60 ± 22 μg/day). Endothelial function, measured as FMD of the brachial artery using ultrasound, was calculated in two groups. Endothelial function was evaluated by assessing 1-min postischemic FMD of the brachial artery. Results FMD was lower in patients with CS than that in those without (11.7 ± 4.8% vs. 15.8 ± 3.2%, P = 0.0001, respectively). There was no significant difference between two groups regarding baseline diameter of brachial artery. But, hyperemia diameter was lower in patients with CS than without CS (3.6 ± 0.22 mm vs. 3.9 ± 0.19 mm, P = 0.04, respectively) Conclusion Endothelium-dependent FMD may impair in patients with CS compared to controls. Measurement of endothelial function may identify high-risk individuals early and therapy to reduce or retard endothelial dysfunction in patients with CS may lead to decreased cardiovascular morbidity and mortality.     

Differentiating clinical and echocardiographic characteristics of chordal rupture detected in patients with rheumatic mitral valve disease and floppy mitral valve: impact of the infective endocarditis on chordal rupture.

AIMS: We aimed to compare the clinical and echocardiographic correlates of chordal rupture in patients with rheumatic mitral valve disease and floppy mitral valve. METHODS AND RESULTS: The study group comprised of 224 patients who underwent transthoracic and transesophageal echocardiography because of the severe mitral regurgitation. Chordal rupture was detected in 58 (25.9%) out of the 224 patients, in 33 out of the 83 (39.7%) patients with floppy mitral valve, and in 25 out of the 141 (17.7%) patients with rheumatic mitral valve disease. Chordal rupture was more frequently associated with anterior leaflet (80%) in patients with rheumatic mitral valve disease, and posterior leaflet (72.7%) in patients with floppy mitral valve (p<0.05). Univariate correlates of chordal rupture were age, male sex, posterior mitral leaflet thickening and chordal elongation in patients with floppy mitral valve (p<0.05), and chordal shortening (p<0.0001) and infective endocarditis involving mitral anterior leaflet (p<0.05) in rheumatic group. Independent predictors of chordal rupture were age (>50 years), posterior mitral leaflet thickness (> or =0.45cm), and male sex (p<0.05) in patients with floppy mitral valve while infective endocarditis involving mitral anterior leaflet (p<0.05) in patients with rheumatic mitral valve disease. Patients with chordal rupture due to floppy mitral valve had an older age (p<0.0001), a male dominance, longer mitral leaflets and chordae, and a larger mitral annulus circumference (p<0.05) as compared to those with rheumatic chordal rupture. Despite the comparable severity of mitral regurgitation and left atrial diameters between the two groups of chordal rupture (p>0.05), functional class and pulmonary artery systolic pressure were higher, and atrial fibrillation, acute deterioration, infective endocarditis, mitral leaflet rupture and need for mitral valve surgery in the 3 months were more frequent in rheumatic chordal rupture subgroup (p<0.05). CONCLUSION: Chordal rupture seems to be more frequently associated with anterior mitral leaflet in rheumatic mitral valve disease, whereas it was the posterior leaflet in floppy mitral valve. Chordal rupture was related to male sex, older age, posterior leaflet thickening, and chordal elongation in patients with floppy mitral valve. However, infective endocarditis, acute deterioration, and need for early mitral surgery were more frequent in patients with rheumatic chordal rupture.     

Epinephrine-secreting cystic pheochromocytoma presenting with an incidental adrenal mass: a case report and a review of the literature

Cystic adrenal masses are a relatively rare condition, and are usually nonfunctioning and asymptomatic. Differential diagnosis includes pheochromocytoma (PHEO) and adrenal carcinoma; 8-10% of patients with PHEO may be completely asymptomatic. Moreover, fewer than 10% of PHEOs secrete pure epinephrine. We report a case of a E-secreting pure cystic PHEO presenting with an incidental adrenal mass. A 49-year-old Turkish woman was hospitalized at Farabi Hospital for further examinations of a right adrenal cystic mass with a thick wall that was incidentally discovered by abdominal ultrasonography during examination for nausea, vomiting, headache, and angina-like chest pain in another hospital. On admission, her blood pressure was 100/60 mmHg. Tension Holter monitoring revealed paroximal hypertension (178/136 mmHg) and hypotension (78/54 mmHg) attacks. Of urinary catecholamines and its metabolites, only urine metanephrine was markedly increased, despite a urine epinephrine level near the upper limit of normal ranges. Abdominal computed tomography and magnetic resonance imaging studies revealed a cystic round tumor approx 5 cm in diameter, located in the right adrenal gland. Right adrenalectomy was performed; the surgical specimen revealed pure cystic PHEO. Postoperatively, the urine metanephrine level returned to normal range and urine epineprine level was decreased approx 60%. In conclusion, a diagnosis of E-secreting PHEO should be considered in patients with nonspecific symptoms, presenting with an incidental cystic adrenal mass, even in the absence of hypertension.     

HLA-DR B1 and DQ B1 polymorphisms in patients with coronary artery ectasia

OBJECTIVES: The purpose of our study was to evaluate the significance of polymorphisms in HLA class II genes in coronary artery ectasia (CAE) patients. METHODS AND RESULTS: Twenty-six patients with CAE without associated cardiac defects were enrolled in the study. CAE was defined as luminal dilation of 1.5- to 2.0-fold of normal limits. Ninety-five healthy subjects who were donors for different organ transplantations, were chosen as control group. Physical examination, electrocardiography and chest X-ray were completely normal in these cases. Both the patients and the control group were screened and compared for their HLA class II genotypes. HLA-DR B1*13, DR16, DQ2 and DQ5 genotypes were significantly more frequent in the patient group.When the known risk factors of coronary heart disease were compared in the patients carrying these genotypes with the non-carrying group, no significant differences were encountered. CONCLUSIONS: HLA-DR B1*13, DR16, DQ2 and DQ5 may be associated with the pathogenesis and increase the risk of CAE.     

Aberrant right ventricular branch of right coronary artery with mitral valve prolapse

A 37-year-old man presented with a three-week history of chest pain. Transthoracic echocardiography demonstrated a mitral valve prolapse and mild mitral insufficiency. Coronary angiography showed normal left main, circumflex, left anterior descending and right coronary arteries; however, the right ventricular branch of the right coronary artery had a separate ostium. Concomitant congenital heart abnormalities have been observed with coronary artery anomalies. Primary congenital coronary and valvular anomalies may have genetic heredity. In the present case, mitral valve prolapse was accompanied by a right ventricular coronary artery origin anomaly which, to the best of our knowledge, is the first report in the literature in which both anomalies presented together.     

Effects of thyroxin therapy on cardiac function in patients with subclinical hypothyroidism: index of myocardial performance in the evaluation of left ventricular function

OBJECTIVE: We investigated the effects of thyroxine (T4) therapy on the cardiac function in subclinical hypothyroidism (SHT) by using the index of myocardial performance (IMP) and the conventional echocardiographic parameters. METHODS: Forty-five SHT patients (F/M:38/7, age 39.9+/-7.9) and 29 healthy subjects (F/M:25/4, age 38.3+/-8.6) were studied. Patients were randomly assigned, in a double-blind manner to receive T4 therapy (group I) or a placebo (group II) and for a period of up to 12 months, were followed up using thyroid function tests and both conventional and Doppler echocardiographic measurements. RESULTS: At the baseline, the SHT patients has a significantly higher isovolumic relaxation time (IRT) (98.3+/-23.7 vs. 81.7+/-14.7<0.01), IMP (0.52+/-0.06 vs. 0.42+/-0.05; P<0.001), A max (late mitral peak velocity) (83.4+/-12.6 vs. 74.3+/-13.5; P<0.01) and significantly lower (early mitral peak velocity) Emax/Amax ratio (1.19+/-0.18 vs. 1.34+/-0.17; P<0.01) than the individuals in the control group. In group I, the thyroid hormone profile became normalized after 1 year of L-T4 therapy, but there was no significant change in the left ventricular (LV) morphology or systolic function. After 1 year of follow-up, group I showed a significant reduction of MPI (0.53+/-0.05 vs. 0.42+/-0.07; P<0.001), Amax (84.2+/-13.7 vs. 74.5+/-11; P<0.001) and IRT (98.6+/-23.7 vs. 82.9+/- 23.3; P<0.001) along with a normalization of the E/A ratio (1.17+/-0.16 vs. 1.33+/-0.19; P<0.001). Conversely, no change was observed in group II. CONCLUSIONS: An impairment of left ventricular diastolic function, which may be reversible with T4 therapy, was observed in the SHT patients, and IMP may be useful in the evaluation of LV myocardial dysfunction in these patients.     

Thyroid disorders and hypercoagulability

Various abnormalities of coagulation and fibrinolysis, ranging from subclinical laboratory abnormalities to clinically significant disorders of hemostasis, but rarely major hemorrhage or thromboembolism, may occur in patients with thyroid diseases. This review discusses the relationships between thyroid dysfunction and the coagulation/fibrinolytic system. According to the recent literature, most of the coagulation/fibrinolytic abnormalities associated with thyroid dysfunction are the consequences of direct effects of thyroid hormones on the synthesis of various hemostatic parameters. Thyroid autoimmunity may also modify the processes of secondary hemostasis. Hyperthyroidism is generally associated with hypercoagulability and hypofibrinolysis, whereas the hemostatic profile in hypothyroidism depends on the severity of the disease. Both hypercoagulable and hypocoagulable states including increased fibrinolytic activity have been reported in hypothyroidism. Few data are available on hemostasis in subclinical thyroid diseases. In conclusion, adequate further prospective clinical studies of high quality including a larges series of patients are needed to explain the degree and type of coagulation/fibrinolytic abnormalities in patients with thyroid diseases.     

The effects of rosiglitazone and metformin on inflammation and endothelial dysfunction in patients with type 2 diabetes mellitus

Diabetic patients have a markedly increased risk of cardiovascular disease compared with non-diabetics. Two drug groups today target insulin resistance; biguanides and thiazolidinediones. In addition, these may have other effects on cardiovascular risk factors. The aim of this study was to evaluate the effects of metformin and rosiglitazone on non-traditional cardiovascular risk factors. Forty type 2 diabetic patients were randomized into metformin and rosiglitazone groups. After receiving the optimal doses, the patients were monitored for 12 weeks. Biochemical parameters, lipid parameters, CRP, insulin, c-peptide, and HbA1c levels were analyzed. VWF, PAI-1, ICAM-1, TNF-α, IL-6, E-selectin, and fibrinogen levels were measured in order to assess coagulation status and endothelial dysfunction. In the metformin group, body mass index, PPG, HbA1c, IL-6, ICAM-1, and TNF-α levels were significantly decreased after 12 weeks compared with the basal levels. IL-6 levels decreased from 75 pg/ml ± 20 to 42 pg/ml ± 9 (P 0.023) and TNF- α levels from 61 pg/ml ± 31 to 39 pg/ml ± 10 (P 0.018). In the rosiglitazone group, FPG, PPG, HbA1c, insulin, HOMA-IR, IL-6, and TNF-α levels decreased significantly after 12 weeks compared with the basal levels. IL-6 levels decreased from 78 pg/ml ± 21 to 41 pg/ml ± 9 (P 0.028) and TNF-α levels from 62 pg/ml ± 19 to 37 pg/ml ± 10 (P 0.012). At the end of the study, no significant differences were determined between groups. Insulin resistance and type 2 diabetes are strongly associated with low grade inflammation. Both metformin and rosiglitazone were effective in controlling inflammatory markers in addition to metabolic parameters.     

In vivo effect of losartan on platelet aggregation in patients with hypertension

The angiotensin II receptor, losartan, has been found to inhibit platelet aggregability to some extent in in vitro experiments. There have been conflicting results about the in vivo effects of losartan. We sought to clarify the in vivo effect of losartan on platelet aggregation. Forty patients with grade I essential hypertension were treated with losartan for 3 weeks. Platelet aggregation tests with adenosine diphosphate (ADP) and ristocetin were analyzed and compared before and at the end of the study. Losartan effectively decreased systolic (SBP) and diastolic (DBP) blood pressure. Mean SBP before and after treatment was 159.6 ± 12.8 and 149.2 ± 17.3mmHg, respectively. Mean DBP decreased from 93.7 ± 8.2 to 87.7 ± 10.3mmHg after treatment. The results of the platelet aggregation tests with ADP and ristocetin were not significantly different when both rate and amplitude of maximal aggregation were included. Peak platelet aggregation with ADP regarding the lowest light transmission in the aggregometer was 59.8% ± 24.3% before and 58.3% ± 18.1% after the treatment. The same variables with ristocetin were 66.8% ± 21.6% and 60.8% ± 23.3%, respectively. In vivo effects of losartan on platelet aggregation with ADP and ristocetin were insignificant.