Mehmet Agirbasli

Comparative effect of angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor antagonism on plasma fibrinolytic balance in humans.

Angiotensin-converting enzyme (ACE) inhibition significantly decreases plasminogen activator inhibitor-1 (PAI-1) without altering tissue plasminogen activator (tPA) during activation of the renin-angiotensin-aldosterone system in humans. Because ACE inhibitors and angiotensin II type 1 (AT(1)) receptor antagonists differ in their effects on angiotensin II formation and bradykinin degradation, the present study compared the effect of equivalent hypotensive doses of an ACE inhibitor and AT(1) antagonist on fibrinolytic balance. Plasma PAI-1 antigen, tPA antigen, plasma renin activity, and aldosterone were measured in 25 normotensive subjects (19 white, 6 black; 14 men, 11 women; mean age 38.5+/-1.8 years; mean body mass index 25.3+/-0.7 kg/m(2)) during low salt intake alone (10 mmol Na/d), low salt intake + quinapril (40 mg PO bid), and low salt intake + losartan (50 mg PO bid). Compared with low salt alone (systolic blood pressure [BP] 118.8+/-2.2 mm Hg), both quinapril (106.3+/-2.5 mm Hg, P<0.001) and losartan (105.4+/-2. 8 mm Hg, P<0.001) reduced BP. No statistical difference was found between quinapril and losartan in their BP lowering effect. Losartan (P=0.009), but not quinapril, lowered heart rate. Both drugs significantly lowered aldosterone (P<0.001 versus low salt alone for each); however, this effect was significantly greater for quinapril than for losartan (P<0.001 for quinapril versus losartan). Treatment with quinapril, but not with losartan, was associated with a decrease in both PAI-1 antigen (P=0.03) and activity (P=0.018). PAI-1 activity was lower during treatment with quinapril than with losartan (P=0.015). The average PAI-1 antigen concentration was 13. 0+/-2.0 ng/mL during low salt alone, 10.5+/-1.6 ng/mL during quinapril treatment, and 12.3+/-2.1 ng/mL during losartan treatment. In contrast, plasma tPA antigen concentrations were reduced during treatment with losartan (P=0.03) but not with quinapril. This study provides the first evidence that ACE inhibitors and AT(1) antagonists differ in their effects on fibrinolytic balance under conditions of activation of the renin-angiotensin-aldosterone system. Further studies are needed to address the mechanism for the contrasting effects of these 2 classes of drugs on fibrinolysis and to define the clinical significance of these differences.

Oxidative stress and severity of coronary artery disease in young smokers with acute myocardial infarction.

BACKGROUND Cigarette smoking increases the oxidative stress mediated vascular dysfunction in young adults. We aimed to investigate the relation between the oxidative stress indices and coronary artery disease (CAD) severity in young patients presenting with acute myocardial infarction (AMI). METHODS Young patients (aged 〈 35 years) who were admitted consecutively to our hospital with a diagnosis of AMI were included in the study. Age matched healthy subjects were selected as controls. Oxidative stress indices including lipid hydroperoxide (LOOH), total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), paraoxonase (PON) and arylesterase (ARE) activities were measured in serum. CAD severity was assessed by calculating the SYNTAX (Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery Study) score. We analyzed the association between the oxidative indices and CAD severity. RESULTS Forty two young patients were admitted to the hospital with AMI (age 32.4 ± 2.6 years; 39 males, 3 females). Current and heavy smoking was commonly observed among the patients (79%). All patients underwent emergency coronary angiography. Twenty-eight healthy subjects were selected as controls. Patients had significantly higher OSI and TOS levels (median, interquartile range) [0.44 (0.26-1.75) vs 0.25 (0.22-0.30), p < 0.001 and 6.0 (4.4-20.8) vs 4.1 (3.7-4.6), p < 0.001], respectively, and lower TAS and LOOH levels [1.6 ± 0.1 vs 1.7 ± 0.1, p = 0.02 and 3.0 ± 0.8 vs 3.6 ± 0.4, p = 0.001], respectively, compared to the control group. CAD severity correlated positively with OSI (r = 0.508, p = 0.001) and TOS levels (r = 0.471, p = 0.002). Subjects with an intermediate to high SYNTAX score (≥ 22) demonstrated significantly higher OSI (median, interquartile range) [0.40 (0.34-1.75) vs 0.34 (0.26-0.68), p = 0.01] and TOS [6.9 (4.4-20.8) vs 5.8 (4.5-11.4), p = 0.01] levels compared to subjects with low SYNTAX score. CONCLUSIONS Oxidative stress is an important contributor to CAD severity among young smokers. Elevated OSI and TOS levels reflect disease severity and vascular damage related to heavy smoking in early onset CAD.

Situs inversus with hypertrophic cardiomyopathy in identical twins

We describe identical twin sisters born to nonconsanguineous, healthy parents. Both twins had situs viscerum inversus and developed hypertrophic cardiomyopathy in adulthood.

Psoriasis and Atherosclerosis: Is There a Need For Novel Biomarkers Assessing Cardiovascular Risk?

Epidemiological studies indicate increased mortality rates in cohorts of patients with psoriatic arthritis (PsA). Psoriasis is associated with an enhanced cardiovascular risk. The excess mortality in psoriasis and PsA is predominantly due to coronary artery disease. The aim of this review is to overview the biomarkers and/or mediators of increased cardiovascular risk in patients with psoriasis and PsA. We searched through Medline/PubMed to retrieve sources on cardiovascular disease (CVD), related risk factors and inflammatory markers in psoriasis and PsA. We analyzed the relationship between psoriasis and novel vascular biomarkers with potential use for preventive studies. Studies underline the importance of considering psoriatic patients as a high-risk population in terms of CVD. Novel biomarkers of inflammation, thrombosis, oxidative stress and atherosclerosis can provide risk stratification and strategies for early detection and treatment of CVD in patients with psoriasis. A better understanding of the association between psoriasis and vascular risk can help the clinician to manage the increased morbidity and mortality related to CVD.

Triple therapy (aspirin, clopidogrel and oral anticoagulant) after percutaneous coronary intervention: another call for personalized medicine.

Studies indicate that 5-7% patients undergoing percutaneous coronary intervention (PCI) have an indication for anticoagulation therapy. Most commonly atrial fibrillation (AF) is the indication. These subjects require triple therapy with aspirin, clopidogrel, and an oral anticoagulant (OAC). Several questions, concerns and challenges exist regarding the duration, benefit, risks and alternatives related to triple therapy. These questions constitute a moving target with recently approved antiplatelet and anticoagulant agents. This brief review will summarize the current literature regarding triple therapy, potential solutions that can mitigate the formidable risk of bleeding. Arising from that discussion, a logical consensus can be developed that should be applicable to studies with novel agents that interfere with homeostasis. The ultimate goal is to enhance cardiovascular outcome and decrease thrombotic and bleeding complications.

Familial hypercholesterolemia with extensive coronary artery disease and tuberous and tendinous xanthomas: A case report and mutation analysis

This is a case report of a 38-year-old Syrian refugee male with early-onset extensive atherosclerosis. The physical and laboratory examination were remarkable with severe xanthomas in the upper and lower extremities and with low-density lipoprotein cholesterol (LDL-C) 417 mg/dL, total cholesterol 495 mg/dL, high-density lipoprotein cholesterol 30 mg/dL, and triglycerides 242 mg/dL. LDL-C level responded poorly to the high-dose statin treatment. The genetic analysis indicated that the patient had a large homozygous deletion in LDL receptor gene including the exons 7-14. A 12-kb deletion had occurred between the 2 Alu repetitive sequences that were oriented in opposite directions, one in intron 6 and the other in intron 14. This deletion eliminated exons 7-14, which exactly corresponded to the entire exon sequence coding the epidermal growth factor precursor homology domain. This deletion in LDL receptor was previously reported. This rare case of homozygous familial hypercholesterolemia presenting with multiple large and widely distributed xanthomas implicates the need for novel treatment options in familial hypercholesterolemia patients. The case is a Syrian refugee and emphasizes the urgent need to address orphan disease in refugee populations throughout the world.

Free estradiol index levels associated with high sensitivity crp levels in male children

Ağırbaşlı M, Tanrıkulu A, Azizy M. Free estradiol index levels associated with high sensitivitiy CRP levels in male children. Turk J Pediatr 2017; 59: 49-55. Biomarkers of inflammation such as high-sensitivity C-reactive protein (hs-CRP) associate with subclinical atherosclerosis. Atherosclerosis is an early onset disease in life. Sex hormones and puberty modulate metabolism in children. Studies indicate that low sex hormone binding globulin (SHBG) levels associate with insulin resistance and metabolic syndrome in children. The aim of this study is to study the correlation between sex hormones and hs-CRP levels in children and adolescents. The study sample was derived from a cross sectional survey on the prevalence of cardiovascular risk factors in a representative sample of school children (8-17 year-old) in Istanbul, Turkey. In addition to anthropometric and biochemical characteristics of cardiovascular risk, sex hormones such as free androgen index, free estradiol index (FEI), SHBG and hs-CRP levels were measured in all study participants: 91 boys (12.4 ± 3.4 years) and 77 girls (12.7 ± 3.4 years) were included in the study. Median (interquartile range) hs-CRP levels were similar among boys and girls [0.36 (0.9) versus 0.45 (0.7) mg/dl, p= 0.725]. Gender stratified analysis displayed that hs-CRP levels positively correlated with FEI levels (r=0.438, p < 0.001) in boys. Linear regression analysis was performed to determine the predictors of hs-CRP. Among covariates of FEI, homeostasis model assessment-estimated insulin resistance, body mass index, age, and SHBG; FEI was shown to significantly and independently predict hs-CRP levels in boys [β=2.758, p < 0.001, 95% confidence interval (CI) for β 1.471-4.045]. FEI levels associate with subclinical inflammation in boys. Future studies may elucidate the role of sex hormone levels in inflammation among children.

Enhanced mRNA expression of plasminogen activator inhibitor-1 in livedoid vasculopathy lesions

AIM Thrombosis and inflammation play an important role in pathophysiology of livedoid vasculopathy (LV). Plasminogen activator inhibitor-1 (PAI-1) is the main physiological inhibitor of fibrinolysis and is a pivotal modulator in a broad range of biological processes. METHOD The study specimens were retrospectively selected from archives of pathology department. We investigated PAI-1 mRNA expression in the paraffin blocks of patients with biopsy-proven LV and controls. We analyzed the presence of thrombus, fibrinoid necrosis, ulcer, and epidermal atrophy in study samples. The correlation between histologic findings and PAI-1 expression was investigated. RESULTS Analyses were performed in 14 LV patients (mean age 31±20, 79% female) and 4 controls (mean age 64±19, 50% female). PAI-1 gene expression was significantly higher in LV compared to the control group (median 7.74 (Iqr:13.94) vs 1.0 (0.31)), P=.011. Histological analysis displayed that fibrinoid necrosis was present on all patients with LV, 61.5% displayed thrombus, 46.2% displayed ulcer, and 15.4% displayed epidermal atrophy. Overall, we did not observe any discerning difference in PAI-1 expression between the LV blocks with or without thrombus, fibrinoid necrosis, or epidermal atrophy, yet the LV specimens that displayed ulcer histologically had higher PAI-1 mRNA expression compared to those without ulcer (median 13.98 (Iqr:19.21) vs 2.86 (5.59)), (P=.046). CONCLUSION PAI-1 mRNA expression is significantly increased in cutaneous lesions of patients with LV. Histological finding of ulcer is associated with increased PAI-1 expression in LV specimen. In the current era of PAI-1 inhibitors, enhanced local PAI-1 expression can form a novel and local therapeutic target in LV.