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- Associations among cerebral microbleeds, cerebral large-artery diseases and endothelial function. [Journal Article]
- Chin Med J (Engl) 2014 Sep; 127(18):3204-8.
Endothelial dysfunction is not only an early stage of atherosclerosis, but also involved in the pathogenesis of cerebral small-vessel diseases. Patients with cerebral microbleeds (CMBs) may have arteriolosclerosis as well as systemic atherosclerosis. However, little is known about the associations among CMBs, atherosclerosis of cerebral large arteries, and endothelial function. Our study aimed to investigate the relationships among them.This was a cross-sectional study. Ninety patients hospitalized in Peking University First Hospital with acute ischemic stroke were enrolled consecutively between November 1, 2007 and January 31, 2008. All subjects underwent transcranial Doppler and carotid color duplex ultrasonography to record the intima-media thickness (IMT) of common carotid artery, carotid plaque, and cerebral artery stenosis. Brain magnetic resonance imaging (MRI) routine sequences and gradient recall-echo T2(*)-weighted imaging were performed to count CMBs with clinical data blindness. Endothelial function was evaluated using flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) of the brachial artery. FMD and NMD were examined by an experienced vascular sonographer using a high-resolution ultrasound.Thirty cases (33.3%) had CMBs with counts ranging from 1 to 30. Both FMD ((9.9±4.8)% vs. (15.2±7.4)%, P = 0.001) and NMD ((13.7±6.1)% vs. (19.0±7.4)%, P = 0.001) were significantly decreased in CMB-positive patients than in CMB-negative patients. No significant relationships were demonstrated between CMBs and intracranial and/or extracranial artery stenosis. The frequencies of CMBs in patients with IMT≥1.0 mm, carotid plaque, and extracranial artery stenosis were 37.5%, 39.4%, and 47.6% respectively, with no significant difference, but much higher than in patients with IMT <1.0 mm (5%, P < 0.05). In Logistic regression analysis, impaired FMD (OR = 5.783, 95% CI 1.652-6.718, P = 0.007) and high pulse pressure (OR = 6.228, 95% CI 1.594-3.891, P = 0.009) were independently associated with the presence of CMBs, as well as previous ischemic stroke. In contrast, NMD was not correlated with CMBs.CMBs may coexist with cerebral atherosclerosis in ischemic stroke. Endothelial dysfunction may play a role in the pathogenesis of CMBs, but may not simply reflect functional alterations of large arteries.
- Effectiveness of ranolazine in patients with type 2 diabetes mellitus and chronic stable angina according to baseline hemoglobin A1c. [Journal Article]
- Am Heart J 2014 Oct; 168(4):457-465.e2.
Ranolazine reduces the frequency of angina and use of sublingual nitroglycerin (SL NTG) in stable angina patients with type 2 diabetes (T2DM). Because pre-clinical data suggest that myocardial late sodium current (INaL), the target of ranolazine, is increased by hyperglycemia, we investigated whether the efficacy of ranolazine was influenced by glycemic control.TERISA was a multinational, randomized, double-blind trial of ranolazine vs. placebo in patients with T2DM and stable angina. Anginal episodes and SL NTG use were recorded daily in an electronic diary. Health status was evaluated at baseline and 8weeks post-randomization using the Seattle Angina Questionnaire (SAQ). The interaction between baseline HbA1c and treatment effect was tested across endpoints using analysis of covariance models, with HbA1c as a continuous variable with restricted cubic splines.The study included 913 patients, with mean age 63.6years, 39% women, mean T2DM duration 7.4years, and mean HbA1c of 7.3%. Heterogeneity of efficacy by HbA1c was observed for the primary endpoint of angina frequency (Pinteraction = .027), the key secondary endpoint of SL NTG use (Pinteraction = .030), SAQ angina frequency (Pinteraction = .001), and SAQ treatment satisfaction (Pinteraction = .025) with greater efficacy of ranolazine in those with higher HbA1c values, increasing continuously from HbA1c levels >6.5%.Among patients with T2DM and stable angina, the therapeutic benefits of ranolazine were greater in those with higher HbA1c values. These data suggest that ranolazine is particularly beneficial in patients with stable angina who have suboptimally controlled T2DM.
- A cost analysis of the impact of a new intravenous antihypertensive in managing perioperative blood pressure during cardiac surgery. [JOURNAL ARTICLE]
- Hosp Pract (1995) 2014 Aug; 42(3):26-32.
Objective: To examine the impact of intravenous antihypertensive selection on hospital health resource utilization using data from the Evaluation of CLevidipine In the Perioperative Treatment of Hypertension Assessing Safety Events (ECLIPSE) trials. Methods: Analysis of ECLIPSE trial data comparing clevidipine to nitroglycerin, sodium nitroprusside, and nicardipine and unit costs based on the Premier Hospital database to assess surgery duration, time to extubation, and length of stay (LOS) with the associated cost. Results: A total of 1414 patients from the ECLIPSE trials and the Premier hospital database were included for analysis. The duration of surgery and postoperative LOS were similar across groups. The time from chest closure to extubation was shorter in patients receiving clevidipine group compared with the pooled comparator group (median 7.0 vs 7.6 hours, P = 0.04). There was shorter intensive care unit (ICU) LOS in the clevidipine group versus the nitroglycerin group (median 27.2 vs 33.0 hours, P = 0.03). A trend toward reduced ICU LOS was also seen in the clevidipine compared with the pooled comparator group (median 32.3 vs 43.5 hours, P = 0.06). The costs for ICU LOS and time to extubation were lower with clevidipine than with the comparators, with median cost savings of $887 and $34, respectively, compared with the pooled comparator group, for a median cost savings of $921 per patient. Conclusions: Health resource utilization across therapeutic alternatives can be derived from an analysis of standard costs from hospital financial data to matched utilization metrics as part of a randomized controlled trial. In cardiac surgical patients, intravenous antihypertensive selection was associated with a shorter time to extubation in the ICU and a shorter ICU stay compared with pooled comparators, which in turn may decrease total costs.
- Acupoint application in patients with chronic stable angina pectoris: study protocol of a randomized, double-blind, controlled trial. [Journal Article]
- Evid Based Complement Alternat Med 2014.:619706.
Background.Chronic stable angina pectoris (CSAP) is a major syndrome of ischemic heart disease (IHD). CSAP manifests as chest pain or discomfort and affects patients' quality of life. Acupoint application (AP) has been reported to be effective for managing the symptoms of CSAP, but the evidence is not convincing. Therefore, we designed a randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy of AP in the treatment of CSAP. Methods and Analysis. Two hundred participants with CSAP will be randomly assigned in a 1 : 1 : 1 : 1 ratio into 4 groups. All participants will receive 12 sessions of treatment in 4 weeks and the same basic treatment procedure. The participants will be visited and assessed for 12 weeks, including a 4-week screening, a 4-week treatment phase, and a 4-week follow-up phase. The primary outcome is the change in the total frequency of self-reported angina attack at 4th week compared with the baseline. The secondary outcomes include the intensity of angina pain, consumption of nitroglycerin or Suxiao Jiuxin pills, CCS angina classification, SAQ, SAS and SDS score. Ethics. The study protocol has been reviewed and approved by the Sichuan Regional Ethics Review Committee on TCM (number 2013kl-001). This trial is registered with clinicaltrials.gov NCT02029118.
- Comparison of the Seattle Angina Questionnaire With Daily Angina Diary in the TERISA Clinical Trial. [JOURNAL ARTICLE]
- Circ Cardiovasc Qual Outcomes 2014 Sep 23.
As new techniques emerge to quantify patients' health status, new opportunities are created to validate patient-reported outcome questionnaires. The Seattle Angina Questionnaire (SAQ), a widely used coronary artery disease-specific health status tool, has not been validated against daily records of angina frequency and sublingual nitroglycerin (SL NTG) use. Additional evidence supporting the validity of the SAQ could justify its broader use as an outcome for clinical studies designed to evaluate treatments that may improve patients' symptoms, function, and quality of life.We used data from 917 patients with type 2 diabetes mellitus, coronary artery disease, and stable angina from the multinational Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina (TERISA) trial. The number of angina episodes and SL NTG used were recorded and transmitted daily using an electronic diary. In cross-sectional analyses, there was a strong relationship between the 2 SAQ angina frequency questions (ie, frequency of angina and SL NTG use) and the corresponding diary responses, with correlation coefficients of -0.64 for angina frequency (95% confidence interval,-0.68 to -0.60) and -0.69 for SL NTG use (95% confidence interval, -0.73 to -0.66). Longitudinally, changes in SAQ angina frequency scores from day 1 to week 8 also correlated with changes in angina frequency (-0.42; 95% confidence interval, -0.48 to -0.30) and SL NTG use by diary (-0.38; 95% confidence interval, -0.43 to -0.32) over the corresponding time period. Correlations were similar when stratified by age, sex, or geography.In a multinational cohort of patients with stable angina, the SAQ angina frequency domain was significantly correlated, both cross sectionally and longitudinally, with daily diary entries of angina frequency and SL NTG use. These data further support the validity of the SAQ angina frequency domain across a broad spectrum of patients with stable angina.http://www.clinicaltrials.gov. Unique identifier: NCT01425359.
- [Effect of verapamil and nitroglycerin on transplanted lung function in canines]. [English Abstract, Journal Article]
- Zhong Nan Da Xue Xue Bao Yi Xue Ban 2014 Aug; 39(8):802-6.
To investigate the protective effect of combined administration of verapamil and nitroglycerin on the function of canine transplanted lungs.Twenty orthotopic left lung transplantations were performed in 40 canines, which were randomly divided into 4 groups. In group I (control), the donor lungs were perfused and preserved with LPD solution, while group II with LPD solution plus verapamil 0.1 g/L, group III with LPD solution plus nitroglycerin 0.1g/L, and group IV with LPD solution plus verapamil 0.1 g/L and nitroglycerin 0.1 g/L. Hemodynamics and graft gas exchange were assessed 0, 2 and 4 h after the operation. The lung grafts were harvested to measure the wet/dry weight ratio, malondialdehyde (MDA) contents and superoxide dismutase (SOD) activity.Compared with group I, II and III, the mean pulmonary artery pressure (MPAP), pulmonary vascular resistance index (PVRI), partial pressure of oxygen in arterial blood (PaO2), dynamic compliance (Cdyn) and alveolar-arterial oxygen tension volume [P(A- a)O2] in group IV were improved significantly (P<0.05). No significant difference in the partial pressure of carbondioxide (PaCO2) and peak inspiratory pressure (PIP) was observed in the 4 groups (P>0.05). In group IV, the wet/dry weight ratio and MDA contents were lower than those in the other 3 groups, and the SOD activity was significantly higher than that of the other 3 groups (P<0.05).Verapamil and nitroglycerin in LPD solution can protect the respiratory function of canine lung grafts by attenuating pulmonary edema and oxidative stress.
- Combined coronary lumen and vessel wall magnetic resonance imaging with i-T2prep: influence of nitroglycerin. [JOURNAL ARTICLE]
- Int J Cardiovasc Imaging 2014 Sep 9.
It has been shown that sublingual nitroglycerin (NTG) improves image quality of coronary lumen magnetic resonance angiography. Our aim was to investigate the influence of NTG on coronary lumen and vessel wall image quality using a combined, single sequence approach (i-T2prep), which is able to image both within the known time frame of action of NTG. Ten healthy volunteers underwent right coronary artery lumen and vessel wall imaging using the i-T2prep sequence before and after administration of NTG. Image quality was assessed qualitatively and quantitatively. Diameter, length and wall thickness were also measured using dedicated semi-automatic software. NTG induced coronary vasodilatation (lumen diameter increased from 2.16 ± 0.32 to 2.52 ± 0.59 mm; p = 0.036). As a result, visualized lumen length (9.8 ± 2.6 to 11.4 ± 3.3 cm; p = 0.025) and qualitative lumen image quality (median 3 (interquartile range 2-3.25) vs. median 3 (interquartile range 3-4); p = 0.046) both improved. Vessel wall imaging also demonstrated a significant improvement in vessel wall sharpness after NTG (24.8 vs. 27.3 %; p = 0.036). This study demonstrates the benefits of NTG for coronary lumen and vessel wall imaging using a combined sequence, i-T2prep. The methodology described here has great potential for future pathophysiological studies.
- The impact of decreases in air temperature and increases in ozone on markers of endothelial function in individuals having type-2 diabetes. [JOURNAL ARTICLE]
- Environ Res 2014 Sep 5.:331-338.
Several studies have reported an association between air pollution and endothelial dysfunction, especially in individuals having diabetes. However, very few studies have examined the impact of air temperature on endothelial function. The objective of this analysis was to investigate short-term effects of temperature and ozone on endothelial function in individuals having diabetes. Moreover, we investigated interactive effects between air temperature and air pollution on markers of endothelial function. Between November 2004 and December 2005 flow-mediated dilatation (FMD), nitroglycerin-mediated dilatation (NTGMD) and several blood markers representing endothelial function were measured using brachial artery ultrasound on four consecutive days in 22 individuals with type-2 diabetes mellitus in Chapel Hill, North Carolina (USA). Daily measurements of meteorological parameters, ozone and particulate matter with an aerodynamic diameter ≤2.5µm (PM2.5) were obtained from fixed monitoring sites. We used additive mixed-models adjusting for time trend, day of the week, relative humidity and barometric pressure to assess temperature and ozone associations with endothelial function. A 1°C decrease in the 24-h temperature average was associated with a decrease in mean FMD on the same day (-2.2% (95%-confidence interval:[-4.7;0.3%])) and with a delay of one and four days. A temperature decrement also led to an immediate (-1.7%[-3.3;-0.04]) decrease in NTGMD. Moreover, we observed an immediate (-14.6%[-26.3;-2.9%]) and a one day delayed (-13.5%[-27.0; 0.04%]) decrease in FMD in association with a 0.01ppm increase in the maximum 8-h moving average of ozone. Temperature effects on FMD strengthened when PM2.5 and ozone concentrations were high. The associations were similar during winter and summer. We detected an association between temperature decreases and ozone increases on endothelial dysfunction in individuals having diabetes. We conclude that endothelial dysfunction might be a possible mechanism explaining cardiovascular events in association with environmental stimuli.
- Topical Nitroglycerin Ointment for Treatment of Acute Hypertension in Hospitalized Inpatients. [JOURNAL ARTICLE]
- J Cardiovasc Pharmacol Ther 2014 Sep 4.
Hypertension in the hospital setting is common; however, guidelines provide limited guidance specific to the inpatient setting. Acute antihypertensive treatment options can be limited in this setting by monitoring requirements of intravenous medications and patients' inability to take oral medications. A possible treatment choice used to treat acute hypertension is nitroglycerin ointment. Nitroglycerin is not approved by the Food and Drug Administration for this condition, and limited evidence exists to support this indication.To evaluate the statistical and clinical effectiveness of nitroglycerin ointment as a treatment option for acute hypertension based on a 20 mm Hg or greater reduction in systolic blood pressure.A retrospective chart review at a large tertiary community teaching hospital was performed on all adult noncardiac inpatients with an episode of acute hypertension that resulted in the administration of nitroglycerin ointment.Seventy-two patients met inclusion criteria with a total of 112 applications of nitroglycerin ointment. Of the 112 applications, systolic blood pressure decreased 20 mm Hg or more in 42% of occurrences with a median decrease of 16 mm Hg.Study results suggest possible efficacy of nitroglycerin ointment for the treatment of acute hypertension in noncardiac hospitalized patients.
- Prognostic impact of chronic nitrate therapy in patients with vasospastic angina: multicentre registry study of the Japanese coronary spasm association. [JOURNAL ARTICLE]
- Eur Heart J 2014 Sep 4.
Although nitrates are widely used as a concomitant therapy with calcium channel blockers (CCBs) for vasospastic angina (VSA), their prognostic contribution remains unclear. The present study aimed to examine the prognostic impact of chronic nitrate therapy in patients with VSA.A total of 1429 VSA patients (median 66 years; male/female, 1090/339) were enrolled. The primary endpoint was defined as major adverse cardiac events (MACE). The propensity score matching and multivariable Cox proportional hazard model were used to adjust for selection bias for treatment and potential confounding factors. Among the study patients, 695 (49%) were treated with nitrates, including conventional nitrates [e.g. nitroglycerin (GTN), isosorbide mono- and dinitrate] in 551 and nicorandil in 306. Calcium channel blockers were used in >90% of patients. During the median follow-up period of 32 months, 85 patients (5.9%) reached the primary endpoint. Propensity score-matched analysis demonstrated that the cumulative incidence of MACE was comparable between the patients with and those without nitrates [11 vs. 8% at 5 years; hazard ratio (HR): 1.28; 95% confidence interval (CI): 0.72-2.28, P = 0.40]. Although nicorandil itself had a neutral prognostic effect on VSA (HR: 0.80; 95% CI: 0.28-2.27, P = 0.67), multivariable Cox model revealed the potential harm of concomitant use of conventional nitrates and nicorandil (HR: 2.14; 95% CI: 1.02-4.47; P = 0.044), particularly when GTN and nicorandil were simultaneously administered.Chronic nitrate therapy did not improve the long-term prognosis of VSA patients when combined with CCBs. Furthermore, the VSA patients with multiple nitrates would have increased risk for cardiac events.