Anna Dobosiewicz

Simvastatin reduces sympathetic activity in men with hypertension and hypercholesterolemia

Beyond their hypolipidemic effect, statins reduce cardiovascular risk in hypertensive subjects via various mechanisms; one suggested mechanism is that they reduce sympathetic activity. We investigated the hypothesis that simvastatin decreased muscle sympathetic nerve activity (MSNA) in 31 hypertensive subjects with hypercholesterolemia (aged 38.7±10 years). In this randomized, placebo-controlled, double-blinded study, patients were treated with simvastatin (40 mg day−1; n=15) or placebo (n=16) for 8 weeks. Before and after treatment, we measured MSNA, blood pressure and heart rate. Baroreceptor control of the heart rate, or baroreceptor sensitivity (BRS), was computed by the sequence method, a cross-analysis of systolic blood pressure and the electrocardiogram R–R interval. Blood samples were tested for plasma levels of catecholamines, neuropeptide Y, aldosterone, endothelin and renin activity. Simvastatin significantly reduced MSNA (from 36.5±5 to 27.8±6 bursts per min, P=0.001), heart rate (from 77±6.7 to 71±6.1 beats per min, P=0.01) and both total and low-density lipoprotein cholesterol (from 249±30.6 to 184±28.3 mg dl−1, P=0.001 and from 169±30.6 to 117±31.2 mg dl−1, P=0.01, respectively). Simvastatin also improved BRS (from 10.3±4.1 to 17.1±4.3 ms per mm Hg, P=0.04). No changes were observed in systolic or diastolic blood pressures, or in plasma levels of catecholamines, neuropeptide Y, endothelin, aldosterone and renin activity. After simvastatin therapy, MSNA and BRS were inversely related (r=−0.94, P<0.05). In conclusion, we found that, in patients with hypertension and hypercholesterolemia, simvastatin reduced MSNA, and this was related to increased baroreceptor sensitivity.

The effect of enalapril and telmisartan on clinical and biochemical indices of sympathetic activity in hypertensive patients.

Objective. To compare the effect of ARB and ACE inhibitor on sympathetic activity in 32 hypertensives. Design and Methods. After a four-week wash-out period, patients were randomized to four weeks of therapy with enalapril or telmisrtan, with crossover to another drug for another four weeks. Blood pressure (BP), NPY, and catecholamine levels and HRV (frequency analysis) were measured during wash-out, in basal condition, and after postural stimulation test (PST). Results. Both drugs significantly reduced BP and NPY as compared to initial values, while no differences in BP and NPY between drugs were observed. Increase in NPY during PST was significantly higher in the enalapril than in the telmisartan group and during the wash-out period. No differences between enalapril and telmisartan in plasma catecholamines were observed. Telmisartan decreased low frequency/high frequency ratio as compared to initial values and enalapril values. Conclusions. Despite similar BP control, telmisartan attenuated autonomic balance more effectively than enalapril.

Improvement in Quality of Life and Hemodynamics in Chronic Thromboembolic Pulmonary Hypertension Treated With Balloon Pulmonary Angioplasty

BACKGROUND The effect of balloon pulmonary angioplasty (BPA) on improvement in functional and hemodynamic parameters in chronic thromboembolic pulmonary hypertension (CTEPH) is known, but the quality of life (QoL) of patients treated with BPA has never been studied before.Methods and Results:Twenty-five patients with inoperable or persistent CTEPH were enrolled in the study and filled out the 36-item Short Form (SF-36v2) questionnaire twice: prior to commencement of BPA treatment and after ≥3 BPA sessions. In addition WHO functional class, distance on the 6-min walk test (6MWT) and hemodynamic parameters such as right atrial pressure (RAP), mean pulmonary artery pressure (mPAP), cardiac index (CI) and pulmonary vascular resistance (PVR) were assessed. QoL improved significantly in all domains, except for physical pain. Improvement in RAP (10.5±3.4 vs. 6.2±2.2 mmHg; P<0.05), mPAP (51.7±10.6 vs. 35.0±9.1 mmHg; P<0.05), CI (2.2±0.5 vs. 2.5±0.4 L/min·m2; P=0.04), PVR (10.4±3.9 vs. 5.5±2.2 Wood units; P<0.05), functional class (96% vs. 20% in WHO class III and IV, P<0.05) and improvement in 6MWT distance (323±135 vs. 410±109 m; P<0.05) was observed. The only significant correlation was between the mental component summary score of QoL after completion of treatment and percentage improvement in the 6MWT (-0.404, P<0.05). CONCLUSIONS Alongside improvement in functional and hemodynamic parameters, BPA also provides significant improvement in QoL.

INTERNAL JUGULAR VEIN VALVE INSUFFICIENCY IN COUGH SYNCOPE

A 53-year-old man with chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea was admitted to the hospital for the evaluation of recurrent syncopal episodes induced by paroxysmal cough. Loss of consciousness was brief, and preceded by the sensation of “fullness in the head.” Syncope was provoked also by prolonged expiration during spirometry, which revealed severe bronchial obstruction. However, oxygen saturation on room air and blood gases were within normal limits. To reproduce reported symptoms, the Valsalva maneuver (VM) was performed with the patient in the supine position with noninvasive, continuous blood pressure monitoring (Finapres, Ohmeda) and finger pulse oximetry. This resulted in a brief loss of consciousness, although no desaturation, decrease in blood pressure, or bradycardia was noted. Transthoracic echocardiography revealed normal left and right ventricular function, mild tricuspid insufficiency, and no evidence of pulmonary hypertension. There was no right-to-left shunt detected on the bubble-contrast study. Neurologic assessment, MRI of the brain, and EEG were unremarkable. Duplex-Doppler examination of extracranial carotid and vertebral arteries showed no stenosis. However, evaluation of the internal jugular veins (IJVs) with the use of color Doppler revealed right internal jugular valve insufficiency with flow reversal during inspiration (figure …

Sequential treatment with sildenafil and riociguat in patients with persistent or inoperable chronic thromboembolic pulmonary hypertension improves functional class and pulmonary hemodynamics

BACKGROUND This study evaluated the incremental effect of riociguat on pulmonary hemodynamics in patients with inoperative or persistent chronic thromboembolic pulmonary hypertension (CTEPH) treated previously with sildenafil. METHODS The retrospective study included 28 patients diagnosed with CTEPH who were ineligible for surgical treatment due to distal thrombi location or who suffered from persistent CTEPH after pulmonary endarterectomy and who were treated with sildenafil at a dose of 25 mg TID for a minimum of 3 months. Sildenafil was subsequently discontinued, and riociguat therapy was started with gradually increasing doses. Right heart catheterization was performed and WHO functional class (FC) was assessed in each patient at three time points: before starting sildenafil therapy (baseline), before the transition to riociguat, and after 3 to 6 months of therapy with riociguat. RESULTS Compared to baseline, the use of sildenafil and riociguat significantly decreased pulmonary vascular resistance (PVR) (10.47 ± 3.56 vs. 7.81 ± 3.58 Wood units, p < 0.001) and mean pulmonary arterial pressure (PAP) (54.1 ± 11.6 vs. 46.1 ± 13.2 mm Hg; p < 0.001) while increasing cardiac output (CO) (4.31 ± 0.88 vs. 4.85 ± 0.87 L/min; p = 0.007). Switching from sildenafil to riociguat reduced PVR by 14% (p = 0.005) and the mean PAP by 6% (p = 0.03) while increasing CO by 11% (p = 0,002). The number of patients with WHO FC III and IV symptoms decreased from 71,4% to 57,1% (p = 0,02) after the change from sildenafil to riociguat. CONCLUSIONS Replacing sildenafil with riociguat in patients with inoperable or persistent CTEPH may improve pulmonary hemodynamics and FC.

The effect of hyperoxia on central blood pressure in healthy subjects

Introduction Hyperoxia increases total peripheral resistance by acting locally but also inhibits the activity of carotid body chemoreceptors. We studied the effect of hyperoxia on central pressure in normotensive subjects. Material and methods Medical air followed by 100% oxygen was provided to 19 subjects (12/7 female/male, age 28.2 ±1.1 years) for 15 min through a non-rebreather mask. Central blood pressure was then measured using applanation tonometry. Results After the first 2 min of hyperoxia, heart rate decreased significantly (65 ±2.6 beats/min vs. 61 ±2.1 beats/min, p = 0.0002). Peripheral and central blood pressure remained unchanged, while hemoglobin oxygen saturation and subendocardial viability ratio index increased (97 ±0.4% vs. 99 ±0.2%, p = 0.03; 168 ±8.4% vs. 180 ±8.2%, p = 0.009). After 15 min of 100% oxygen ventilation, heart rate and peripheral and central blood pressures remained unchanged from the first 2 min. The augmentation index, augmentation pressure and ejection duration increased as compared to baseline values and those obtained at 2 min (–5.1 ±2.9% vs. –1.2 ±2.6%, p = 0.005 and –4.6 ±2.7% vs. –1.2 ±2.6%, p = 0.0015; –1.3 ±0.7 mm Hg vs. –0.2 ±1.2 mm Hg, p = 0.003 and –1.1 ±0.7 mm Hg vs. –0.2 ±1.2 mm Hg, p = 0.012; 323 ±3.6 ms vs. 330 ±3.5 ms, p = 0.0002 and 326 ±3.5 ms vs. 330 ±3.5 ms, p = 0.021, respectively). Conclusions The present study shows that hyperoxia does not affect central blood pressure in young healthy subjects and may improve myocardial blood supply estimated indirectly from applanation tonometry.

SIMVASTATIN REDUCES SYMPATHETIC ACTIVITY IN MEN WITH HYPERTENSION AND MILD HYPERCHOLESTEROLEMIA: PP.32.257

Objectives: Statins might reduce cardiovascular risk in hypertensive subjects far beyond their hypolipidemic effect. Several mechanisms of that action, including reduction of sympathetic activity have been suggested. Therefore we investigated the hypothesis, that simvastatin decreased muscle sympathetic nerve activity (MSNA) in hypertensive subjects with hypercholesterolemia. Design and method: Thirty one hypertensive hypercholesterolemic patients (aged 38.7 ± 10 yrs) participated in randomized, placebo controlled, double blinded study. Patients (n = 15) were assigned to simvastatin (40 mg/day) or placebo (n = 16) and treated for 8 weeks. In all patients before and after therapy MSNA, systolic and diastolic blood pressure, heart rate and baroreceptors sensitivity were measured, and blood samples for plasma catecholamines, neuropeptide Y, aldosteron, endothelin concentrations and plasma renin activity measurements were taken. Results: Simvastatin significantly reduced MSNA (from 36.5 ± 5 to 27.8 ± 6 burst/minute, p = 0.001), heart rate (from 77 ± 6.7 to 71 ± 6.1 beats/min, p = 0.01) and both total and LDL cholesterol (from 249 ± 30.6 to 184 ± 28.3 mg/dL, p = 0.001 and from 169 ± 30.6 to 117 ± 31.2 mg/dL, p = 0.01, respectively). Baroreceptor sensitivity increased during simvastatin therapy (from 10.3 ± 4.1 to 17.1 ± 4.3 ms/mm Hg, p = 0.04), while no changes were observed in systolic and diastolic blood pressure, plasma catecholamines, neuropeptide Y, endothelin, aldosteron concentration and plasma renin activity. MSNA and baroreceptor sensitivity after simvastatin therapy was inversely related (r = - 0.94, p < 0.05). Conclusion: Simvastatin reduced MSNA in patients with hypertension and hypercholesterolemia. MSNA reduction after therapy with simvastatin was related to increased baroreceptor sensitivity.