Endothelial function and sympathetic nervous system activity in patients with Takotsubo syndrome.

BACKGROUND: Takotsubo syndrome (TTS) is an acute cardiomyopathy associated with intense physical or emotional stress. The precise mechanisms of the disease remain unclear. The aim of this study was to study alterations in endothelial function, vascular compliance and structure and muscle sympathetic activity in the stable phase of the disease. METHODS: In this prospective observational study, patients with TTS and controls matched for age, sex, cardiovascular risk factors and medications were recruited. Flow-mediated vasodilatation (FMD) as a measure of endothelial dysfunction was the primary endpoint. Secondary endpoints included measurements of arterial stiffness, carotid atherosclerosis, quality of life and laboratory parameters. In a subset of patients, muscle sympathetic activity was measured before and after stress tests. RESULTS: The study included 22 TTS patients and 21 matched controls. A significant increase in endothelial dysfunction was seen in TTS compared to controls (FMD 3.4±2.4% vs. 4.8±1.9%, p=0.016). No significant differences in arterial stiffness, intima-media thickness, quality of life and laboratory markers including endothelin-1 were noted. TTS patients showed a reduced carotid total plaque area compared to controls (TPA 17.3±15.1 vs 24.7±12.8mm2, p=0.02). A trend of increased muscle sympathetic activity at rest was observed in TTS patients vs. controls (53.5±28.4 vs. 29.4±16.5 bursts/100 heart beats, p=0.09) with no significant differences in muscle sympathetic activity in response to stress. CONCLUSIONS: Our findings underscore the importance of endothelial dysfunction in patients with TTS which may be involved in the pathophysiology of this syndrome. CLINICALTRIALS. GOV IDENTIFIER: NCT01249599.

Beneficial effects of polyphenol-rich olive oil in patients with early atherosclerosis.

PURPOSE: Diets rich in plant-derived polyphenols such as olive oil (OO) and/or catechins such as epigallocatechin 3-gallate (EGCG) have been shown to reduce the incidence of cardiovascular diseases, potentially by improving endothelial function, an important surrogate for atherosclerosis. The possible augmentation of endothelial function with the combined efforts of OO and EGCG is intriguing, yet unknown. METHODS: Eighty-two patients with early atherosclerosis (presence of endothelial dysfunction) were enrolled in this double-blind, randomized trial with 52 completing the study. The aim of the study was to compare the effect of a daily intake of 30 ml simple OO, with 30 ml of EGCG-supplemented OO, on endothelial function as well as on inflammation and oxidative stress after a period of 4 months. Endothelial function was assessed noninvasively via peripheral arterial tonometry (Endo-PAT®). RESULTS: After 4 months, when OO and EGCG-supplemented OO groups were combined, OO significantly improved endothelial function (RHI, 1.59 ± 0.25-1.75 ± 0.45; p < 0.05). However, there were no significant differences in results between the two olive oil groups. Interestingly, with OO supplementation there was a significant reduction in inflammatory parameters: sICAM (196 to 183 ng/mL, p = < 0.001); white blood cells (WBCs) (6.0 × 109/L-5.8 × 109/L, p < 0.05); monocytes (0.48 × 109/L to 0.44 × 109/L, p = 0.05); lymphocytes (1.85 × 109/L to 1.6 × 109/L, p = 0.01); and platelets (242-229 × 109/L, p = 0.047). CONCLUSIONS: Improvement in endothelial dysfunction in patients with early atherosclerosis in association with significant reduction in leukocytes may suggest an important role of early cellular inflammatory mediators on endothelial function. The current study supports one potential mechanism for the role of olive oil, independent of EGCG, modestly supplemented to a healthy cardiovascular diet.

Circulating humanin levels are associated with preserved coronary endothelial function.

Humanin is a small endogenous antiapoptotic peptide, originally identified as protective against Alzheimer's disease, but subsequently also found on human endothelium as well as carotid artery plaques. Endothelial dysfunction is a precursor to the development of atherosclerotic plaques, which are characterized by a highly proinflammatory, reactive oxygen species, and apoptotic milieu. Previous animal studies demonstrated that humanin administration may improve endothelial function. Thus the aim of this study was to test the hypothesis that patients with coronary endothelial dysfunction have reduced systemic levels of humanin. Forty patients undergoing coronary angiography and endothelial function testing were included and subsequently divided into two groups based on coronary blood flow (CBF) response to intracoronary acetylcholine (normal ≥ 50% increase from baseline, n = 20 each). Aortic plasma samples were obtained at the time of catheterization for the analysis of humanin levels and traditional biomarkers of atherosclerosis including C-reactive protein, Lp-Pla(2), and homocysteine. Baseline characteristics were similar in both groups. Patients with coronary endothelial dysfunction (change in CBF = -33 ± 25%) had significantly lower humanin levels (1.3 ± 1.1 vs. 2.2 ± 1.5 ng/ml, P = 0.03) compared with those with normal coronary endothelial function (change in CBF = 194 ± 157%). There was a significant and positive correlation between improved CBF and humanin levels (P = 0.0091) not seen with changes in coronary flow reserve (P = 0.76). C-reactive protein, Lp-Pla(2), and homocysteine were not associated with humanin levels. Thus we observed that preserved human coronary endothelial function is uniquely associated with higher systemic humanin levels, introducing a potential diagnostic and/or therapeutic target for patients with coronary endothelial function.

[Effect of paracetamol (acetaminophen) on blood pressure in patients with coronary heart disease]. / Effekt von Paracetamol auf den Blutdruck bei Patienten mit koronarer Herzkrankheit.

Analgesic drugs, non-steroidal anti-inflammatory drugs and paracetamol (acetaminophen) in particular, belong to the most widely prescribed therapeutic agents. Beside their efficacy in pain relief, these drugs were recently linked to increased cardiovascular risk. Indeed, epidemiological and clinical studies showed that non-selective non-steroidal anti-inflammatory drugs, as well as selective cyclooxygenase-2 inhibitors both may increase blood pressure and cardiovascular events. However, the effect of paracetamol (acetaminophen) on blood pressure and cardiovascular health should not be neglected, too. Unfortunately, long-term randomized controlled trials appropriately powered to evaluate cardiovascular outcomes are lacking. This review summarizes the available data about the effect of paracetamol in particular, on blood pressure and other cardiovascular outcomes.

Acute effect of nitroglycerin on cyclosporine-induced hypertension after cardiac transplantation.

BACKGROUND: Cyclosporine represents a milestone in immunosuppression following organ transplantation. Its use, however, comes at the cost of significant side effects, such as arterial hypertension which is rarely controllable by currently available anti-hypertensive drugs. The aim was to investigate the effect of acute administration of nitroglycerin in heart-transplanted patients with cyclosporine-induced hypertension. METHODS: The sample included 18 cyclosporine-induced hypertensive patients (HTX group) scheduled for elective cardiac catheterization following heart transplantation, as well as 6-matched essential hypertensive patients (HT group). The blood pressure (BP) in the aorta and pulmonary artery, before and after administration of nitroglycerin, was measured simultaneously. RESULTS: After injection of 50 µg and 100 µg nitroglycerin, BP significantly decreased both in HTX (systolic (s) BP p = 0.0001; diastolic (d) BP p = 0.0001) and in controls (sBP p = 0.006; dBP p = 0.05). This reduction was more pronounced in HTX (sBP p = 0.022; dBP p = 0.018 for group-comparison). Following analysis of the data in relation to its individual baseline, a significantly higher reduction of the BP induced by 100 µg nitroglycerin was observed in the HTX group compared to the HT group (p = 0.02 for sBP and p = 0.03 for dBP). 8 +/- 3 minutes after the last nitrate infusion, BP remained significantly reduced compared to baseline in HTX (p <0.001), whereas it came back to baseline in controls. The reduction in sBP was correlated to cyclosporine A levels (p = 0.04 after 50µg nitroglycerin; p = 0.05 after 100 µg nitroglycerin). CONCLUSION: After application of nitroglycerin, sBP is reduced immediately in HTX with uncontrolled cyclosporine-induced hypertension. Further studies are needed to evaluate the long-term effect of nitrates in these patients.

Effect of atazanavir versus other protease inhibitor-containing antiretroviral therapy on endothelial function in HIV-infected persons: randomised controlled trial.

OBJECTIVE: Impaired endothelial function was demonstrated in HIV-infected persons on protease inhibitor (PI)-containing antiretroviral therapy, probably due to altered lipid metabolism. Atazanavir is a PI causing less atherogenic lipoprotein changes. This study determined whether endothelial function improves after switching from other PI to atazanavir. DESIGN: Randomised, observer-blind, treatment-controlled trial. SETTING: Three university-based outpatient clinics. PATIENTS: 39 HIV-infected persons with suppressed viral replication on PI-containing regimens and fasting low-density lipoprotein (LDL)-cholesterol greater than 3 mmol/l. INTERVENTION: Patients were randomly assigned to continue the current PI or change to unboosted atazanavir. MAIN OUTCOME MEASURES: Endpoints at week 24 were endothelial function assessed by flow-mediated dilation (FMD) of the brachial artery, lipid profiles and serum inflammation and oxidative stress parameters. RESULTS: Baseline characteristics and mean FMD values of the two treatment groups were comparable (3.9% (SD 1.8) on atazanavir versus 4.0% (SD 1.5) in controls). After 24 weeks' treatment, FMD decreased to 3.3% (SD 1.4) and 3.4% (SD 1.7), respectively (all p = ns). Total cholesterol improved in both groups (p<0.0001 and p = 0.01, respectively) but changes were more pronounced on atazanavir (p = 0.05, changes between groups). High-density lipoprotein and triglyceride levels improved on atazanavir (p = 0.03 and p = 0.003, respectively) but not in controls. Serum inflammatory and oxidative stress parameters did not change; oxidised LDL improved significantly in the atazanavir group. CONCLUSIONS: The switch from another PI to atazanavir in treatment-experienced patients did not result in improvement of endothelial function despite significantly improved serum lipids. Atherogenic lipid profiles and direct effects of antiretroviral drugs on the endothelium may affect vascular function. TRIAL REGISTRATION NUMBER: NCT00447070.

The vascular endothelium in hypertension.

The vascular endothelium plays a fundamental role in the basal and dynamic regulation of the circulation. Thus, it has a crucial role in the pathogenesis of hypertension. A spectrum of vasoactive substances is synthesised in the endothelium; of these, nitric oxide (NO), prostacyclin (PGI2) and endothelin (ET)-1 are the most important. There is a continuous basal release of NO determining the tone of peripheral blood vessels. Systemic inhibition of NO synthesis or scavenging of NO through oxidative stress causes an increase in arterial blood pressure. Also, the renin-angiotensin-aldosterone system has a major role in hypertension as it has a direct vasoconstrictor effect and important interactions with oxygen free radicals and NO. Prostacyclin, in contrast to NO, does not contribute to the maintenance of basal vascular tone of conduit arteries, but its effect on platelets is most important. ET acts as the natural counterpart to endothelium-derived NO and has an arterial blood pressure-raising effect in man. Anti-hypertensive therapy lowers blood pressure and may influence these different mediators, thus influencing endothelial function. In summary, due to its position between the blood pressure and smooth muscle cells responsible for peripheral resistance, the endothelium is thought to be both victim and offender in arterial hypertension. The delicate balance of endothelium-derived factors is disturbed in hypertension. Specific anti-hypertensive and anti-oxidant treatment is able to restore this balance.