Severity of obstructive sleep apnea and extension of coronary artery disease.

PURPOSE: Obstructive sleep apnea (OSA) is highly prevalent among patients with coronary artery disease (CAD). The relationship between the severity of OSA and the severity of CAD has not been entirely established. The objective was to explore the type of correlation existent between the apnea-hypopnea index and the Gensini score, which provides granularity in terms of CAD extension and severity, in search of a dose-response relationship. METHODS: A cross-sectional study was conducted among patients that underwent cardiac catheterization due to the suspicion of CAD. Coronary lesions were classified according to one's Gensini score. The severity of OSA was determined by the apnea-hypopnea index (AHI), obtainable through a respiratory polysomnography. RESULTS: Eighty patients were eligible for the study. The mean age was 55 years, and 37% had AHI ≥ 15. Forty-four subjects (55%) had a Gensini score of 0, and five had a score < 2, indicating a 25% obstruction in a non-proximal artery; these individuals were considered non-CAD controls; and clinical characteristics were similar between them and CAD cases. Attempts to correlate the AHI with the Gensini score either converting both variables to square root (r = 0.08) or using Spearman's rho (rho = 0.13) obtained small, non-significant coefficients. AHI ≥ 15 was a predictor of a Gensini score ≥ 2 with a large effect size (OR 4.46) when adjusted for age ≥ 55 years, BMI ≥ 25 kg/m2, uric acid, and hypertension. CONCLUSIONS: In patients undergoing coronary angiography due to suspected CAD, moderate-severe OSA was associated with the presence of CAD but no significant correlation was found between the lesion severity and the AHI. Our results suggest that OSA influences CAD pathogenesis but a dose-response relationship is unlikely.

Unprotected left main bifurcation restenosis treated with a 2-stent technique.

The present case report refers to the percutaneous treatment of severe left main stem stenosis as a consequence of proliferative in-stent restenosis of left circumflex coronary with retrograde involvement. A reverse mini-crush technique with 2 stents was described.

Hemodynamic responses to resistance exercise with restricted blood flow in young and older men.

Exercise with blood flow restriction promotes significant improvements, and it has been considered an attractive exercise strategy, especially for older individuals. However, the acute cardiovascular responses to resistance exercise with blood flow restriction (BFR) are not fully known. The purpose of this study was to evaluate the hemodynamic responses during resistance exercise with BFR in young and older individuals. We compared hemodynamic responses in 15 young (30 ± 3 years) and 12 older (66 ± 7 years) subjects during low-intensity resistance biceps curl exercise with (BFR-RE) or without (RE) BFR in a random and crossover design. Heart rate (HR), mean blood pressure (MBP), calf blood flow (CBF), and calf vascular resistance (CVR) were evaluated. Both groups presented similar values at baseline. Compared with RE, HR and MBP were higher during BFR-RE for both the groups, and these changes were maintained during the recovery period. In both the groups, BFR-RE elicited larger decreases in CBF and increased CVR. Both groups showed a significant increase in double product during BFR-RE. In conclusion, resistance exercise with BFR elicits greater hemodynamic changes in healthy young and older subjects, with responses of similar magnitudes in both groups. The safety of BFR in clinical practice demands further study in vulnerable populations.

Effect of transcutaneous electrical nerve stimulation on muscle metaboreflex in healthy young and older subjects.

Transcutaneous electrical nerve stimulation (TENS) increases local blood flow. It is not known whether increase in blood flow may be caused by inhibition of sympathetic activity, mediated by muscle metaboreflex activity. The purpose of this study was to evaluate the effect of TENS on metaboreflex activation and heart rate variability (HRV) in young and older individuals. Eleven healthy young (age 25 ± 1.3 years) and 11 healthy older (age 63 ± 4.2 years) were randomized to TENS (30 min, 80 Hz, 150 µs) or placebo (same protocol without electrical output) applied on the ganglion region. Frequency domain indices of HRV and hemodynamic variables were evaluated during the pressor response to static handgrip exercise at 30% of maximal voluntary contraction, followed by recovery with (PECO+) or without (PECO-) circulatory occlusion, in a randomized order. At the peak exercise, the increase in mean blood pressure was attenuated by TENS (P < 0.05), which was sustained during PECO+ and PECO-. TENS promoted a higher calf blood flow and lower calf vascular resistance during exercise and recovery. Likewise, TENS induced a reduction in the estimated muscle metaboreflex control both in young (placebo: 28 ± 4 units vs. TENS: 6 ± 3, P < 0.01) and in older individuals (placebo: 13 ± 3 units vs. TENS: 5 ± 3, P < 0.01). HRV analysis showed similar improvement in sympatho-vagal balance with TENS in young and older individuals. We conclude that application of TENS attenuates blood pressure and vasoconstrictor responses during exercise and metaboreflex activation, associated with improved sympatho-vagal balance in healthy young and older individuals.

Plasma concentrations of efavirenz are associated with body weight in HIV-positive individuals.

BACKGROUND: Efavirenz is among the most widely used antiretroviral drugs. Increased efavirenz exposure has been associated with CNS side effects and also with the chance of emergence of resistance upon treatment interruptions. The objective of this study was to evaluate factors associated with efavirenz plasma concentrations in a cohort of HIV-infected individuals. METHODS: From July 2009 to March 2010, HIV-infected patients with efavirenz as part of antiretroviral therapy (600 mg at night), undetectable viral load for at least 1 year and CD4 cell count >200 cells/mm(3) were consecutively enrolled at the HIV/AIDS ambulatory care unit in southern Brazil. Plasma samples were taken 18-23 h after efavirenz last dose and analysed by validated ultra-performance liquid chromatography. RESULTS: Forty-one subjects were included (21 females). Mean age and weight were 45.4 years and 70.9 kg, respectively. Mean efavirenz plasma concentration was 2.20 ±â€Š2.17 mg/L. Most plasma concentrations (73%) were within the therapeutic window (1-4 mg/L); 17% were below and 10% above the limits. There were no significant associations between efavirenz concentration and age, CD4 cell count, time on antiretroviral treatment and gender. There was significant and inverse correlation between efavirenz concentrations and body weight (P = 0.013) and body mass index (P = 0.001). CONCLUSIONS: In this cohort of well-controlled HIV-positive individuals, patients with lower weight or body mass index had a higher chance of presenting elevated plasma concentrations of efavirenz. Therapeutic drug monitoring to adjust dose might be a helpful tool to decrease efavirenz dose in order to minimize costs and adverse effects.

Erectile dysfunction and coronary artery disease: an association of higher risk in younger men.

INTRODUCTION: The association between erectile dysfunction (ED) and coronary artery disease (CAD) has been described in various settings, but it is unclear if there is an independent interaction with age. AIM: To investigate the interaction of age in the association between ED and CAD. METHODS: This case-control study was conducted among 242 patients referred for elective coronary angiography. One hundred fourteen patients with significant CAD were identified as cases and 128 controls without significant CAD. ED was evaluated by the erectile function domain of the International Index of Erectile Function (IIEF) questionnaire, determined by a score ≤ 25 points. MAIN OUTCOME MEASURES: Significant CAD was based on stenosis of 50% or greater in the diameter in at least one of the major epicardial vessels or their branches. The analysis was conducted in the whole sample and according to the age strata, controlling for the effects of cardiovascular risk factors, testosterone, and C-reactive protein. Results. Patients had on average 58.3 ± 8.9 years. CAD and ED were associated exclusively in patients younger than 60 years (ED in 68.8% of patients with CAD vs. 46.7% of patients without CAD, P = 0.009). The association was independent of cardiovascular risk factors, testosterone and C-reactive protein (risk ratio 2.3, 95% confidence interval from 1.04 to 5.19). Severity of CAD was higher in patients younger than 60 years with ED. CONCLUSIONS: Men with less than 60 years of age who report ED presented a higher risk of having chronic CAD and more severe disease diagnosed by coronary angiography.

Lack of association between plasma myeloperoxidase levels and angiographic severity of coronary artery disease in patients with acute coronary syndrome.

OBJECTIVE: To evaluate the association between plasma myeloperoxidase (MPO) levels and angiographic severity of coronary atherosclerotic lesions in patients with non-ST elevation acute coronary syndrome (ACS). DESIGN AND METHODS: This cross-sectional study examined high-risk ACS patients who underwent coronary angiography within 72 h of the onset of symptoms by measuring their plasma MPO levels after sheath insertion. Gensini score was used to evaluate angiographic severity of coronary artery disease. RESULTS: A total of 48 patients were included in the study. Median MPO levels and Gensini scores were 6.9 ng/mL (4.4-73.5 ng/mL) and 10 (0-87.5), respectively. Spearman's correlation coefficient did not show a significant association between MPO levels and Gensini scores (r (s) = 0.2; p = 0.177). There was no correlation between MPO and age, hypertension, diabetes, leukocyte count, troponin I, CK-MB ≥ 2 × ULN (upper limit of normal), TIMI risk score ≥ 4 and Gensini score in the multivariate analysis. CONCLUSION: Our findings indicate that MPO expression is not associated with anatomical severity of coronary lesions in ACS.

Efficacy comparison of trimetazidine with therapeutic alternatives in stable angina pectoris: a network meta-analysis.

AIMS: To compare the antianginal efficacy of trimetazidine with that of other agents with no influence on heart rate. METHODS AND RESULTS: Medline and Embase databases were searched for blinded, randomized, controlled trials assessing the effects of non-heart-rate-lowering antianginal treatments on exercise tolerance and/or clinical criteria in stable angina patients. All relevant trimetazidine trials including the VASCO trial, the results of which are published herein, were included. A Bayesian network meta-analysis on the summary data was performed. Comparator antianginal agents were considered as a group and in agent/class subgroups. Trials involving ß-blockers, non-dihydropyridine calcium channel blockers, and ivabradine were excluded. 218 trials totaling 19,028 patients were included in at least 1 network analysis. Effects of trimetazidine were statistically significant compared with placebo for exercise tolerance and clinical criteria. Transposition of results into seconds for clinical interpretation of exercise tolerance parameters showed a mean improvement of +46 s (95% credibility interval: 28; 66) for total exercise duration, +55 s (35; 77) for 1-mm ST segment depression (T1), and +54 s (24; 84) for time to onset of angina, in favor of trimetazidine. Differences between trimetazidine and active comparators were not significant when exercise tolerance and clinical criteria were analyzed, with +7 s (-12; 28) for total exercise duration, -1 s (-23; 22) for T1, +8 s (-22; 40) for time to onset of angina, and -0.28 (-1.17; 0.64) attacks per week for trimetazidine compared with antianginal agents as a group. CONCLUSIONS: Trimetazidine efficacy was comparable to that of other non-heart-rate-lowering antianginal treatments in patients with stable angina pectoris.

Physical activity advice only or structured exercise training and association with HbA1c levels in type 2 diabetes: a systematic review and meta-analysis.

CONTEXT: Regular exercise improves glucose control in diabetes, but the association of different exercise training interventions on glucose control is unclear. OBJECTIVE: To conduct a systematic review and meta-analysis of randomized controlled clinical trials (RCTs) assessing associations of structured exercise training regimens (aerobic, resistance, or both) and physical activity advice with or without dietary cointervention on change in hemoglobin A(1c) (HbA(1c)) in type 2 diabetes patients. DATA SOURCES: MEDLINE, Cochrane-CENTRAL, EMBASE, ClinicalTrials.gov, LILACS, and SPORTDiscus databases were searched from January 1980 through February 2011. STUDY SELECTION: RCTs of at least 12 weeks' duration that evaluated the ability of structured exercise training or physical activity advice to lower HbA(1c) levels as compared with a control group in patients with type 2 diabetes. DATA EXTRACTION: Two independent reviewers extracted data and assessed quality of the included studies. DATA SYNTHESIS: Of 4191 articles retrieved, 47 RCTs (8538 patients) were included. Pooled mean differences in HbA(1c) levels between intervention and control groups were calculated using a random-effects model. Overall, structured exercise training (23 studies) was associated with a decline in HbA(1c) level (-0.67%; 95% confidence interval [CI], -0.84% to -0.49%; I(2), 91.3%) compared with control participants. In addition, structured aerobic exercise (-0.73%; 95% CI, -1.06% to -0.40%; I(2), 92.8%), structured resistance training (-0.57%; 95% CI, -1.14% to -0.01%; I(2), 92.5%), and both combined (-0.51%; 95% CI, -0.79% to -0.23%; I(2), 67.5%) were each associated with declines in HbA(1C) levels compared with control participants. Structured exercise durations of more than 150 minutes per week were associated with HbA(1c) reductions of 0.89%, while structured exercise durations of 150 minutes or less per week were associated with HbA(1C) reductions of 0.36%. Overall, interventions of physical activity advice (24 studies) were associated with lower HbA(1c) levels (-0.43%; 95% CI, -0.59% to -0.28%; I(2), 62.9%) compared with control participants. Combined physical activity advice and dietary advice was associated with decreased HbA(1c) (-0.58%; 95% CI, -0.74% to -0.43%; I(2), 57.5%) as compared with control participants. Physical activity advice alone was not associated with HbA(1c) changes. CONCLUSIONS: Structured exercise training that consists of aerobic exercise, resistance training, or both combined is associated with HbA(1c) reduction in patients with type 2 diabetes. Structured exercise training of more than 150 minutes per week is associated with greater HbA(1c) declines than that of 150 minutes or less per week. Physical activity advice is associated with lower HbA(1c), but only when combined with dietary advice.

Long-term complication after LM bifurcation treatment.

Two months after left anterior descending (LAD) artery and left circumflex (LCx) artery bare metal stent implantation, a proliferative subocclusive in-stent restenosis in LCx coronary with severe LM coronary (LM) involvement developed. The present clinical case describes a simplified strategy for unprotected LM percutaneous coronary intervention using two bioabsorbable biolimus-eluting stents without involvement of the LAD coronary using an "L" technique.

Addition of inspiratory muscle training to aerobic training improves cardiorespiratory responses to exercise in patients with heart failure and inspiratory muscle weakness.

BACKGROUND: This small clinical trial tested the hypothesis that the addition of inspiratory muscle training (IMT) to aerobic exercise training (AE) results in further improvement in cardiorespiratory responses to exercise than those obtained with AE in patients with chronic heart failure (CHF) and inspiratory muscle weakness (IMW). METHODS: Twenty-four patients with CHF and IMW (maximal inspiratory pressure <70% of predicted) were randomly assigned to a 12-week program of AE plus IMT (AE + IMT, n = 12) or to AE alone (AE, n = 12). Before and after intervention, the following measures were obtained: maximal inspiratory muscle pressure (PI(max)), peak oxygen uptake (Vo(2)peak), peak circulatory power, oxygen uptake efficiency slope, ventilatory efficiency, ventilatory oscillation, oxygen uptake kinetics during recovery (T(1/2)Vo(2)), 6-minute walk test distance, and quality of life scores. RESULTS: Compared to AE, AE + IMT resulted in additional significant improvement in PI(max) (110% vs 72%), Vo(2)peak (40% vs 21%), circulatory power, oxygen uptake efficiency slope, ventilatory efficiency, ventilatory oscillation, and T(1/2)Vo(2). Six-minute walk distance and quality of life scores improved similarly in the 2 groups. CONCLUSION: This randomized trial demonstrates that the addition of IMT to AE results in improvement in cardiorespiratory responses to exercise in selected patients with CHF and IMW. The clinical significance of these findings should be addressed by larger randomized trials.

Blunted vascular responses but preserved endothelial vasodilation after submaximal exercise in chronic heart failure.

BACKGROUND: Patients with chronic heart failure (CHF) have abnormal vascular responses to acute exercise; however, regular aerobic training improves endothelial function in these patients. We hypothesized that, because of their attenuated vascular responses, CHF patients would present abnormal endothelium-dependent vasodilatation after a single exercise session. METHODS: Thirteen CHF patients and 13 healthy controls participated in two experiments, on different days, using a cross-over design: (i) control (25-min seated at rest), and (ii) a submaximal exercise session (25-min cycling). Measurements of heart rate, blood pressure (BP), venous occlusion plethysmography forearm blood flow (FBF), and reactive hyperemia were made before and after (immediately, 10, 30, 60 min, and 24 h) each experimental condition. RESULTS: CHF patients had no changes in the mean BP throughout the protocols, whereas mean BP was reduced up to 60 min after exercise in controls. In CHF patients, FBF was increased and forearm vascular resistance was reduced up to 10 min after exercise, whereas these changes were sustained up to 30 min after exercise in controls. Reactive hyperemia was significantly increased up to 30 min after exercise in both groups. CONCLUSION: Patients with CHF have increased postexercise FBF and decreased forearm vascular resistance; however, these responses last longer in healthy individuals. Despite the attenuated postexercise vascular responses, patients with CHF respond to a single-cycle exercise session with improved forearm endothelium-dependent vasodilation.

Inspiratory muscle strength as a determinant of functional capacity early after coronary artery bypass graft surgery.

UNLABELLED: Stein R, Maia CP, Silveira AD, Chiappa GR, Myers J, Ribeiro JP. Inspiratory muscle strength as a determinant of functional capacity early after coronary artery bypass graft surgery. OBJECTIVE: To evaluate the effects of a 6-day postoperative in-hospital cardiopulmonary rehabilitation program on inspiratory muscle strength and its potential association with improved functional capacity after coronary artery bypass graft (CABG) surgery. DESIGN: Prospective, randomized controlled trial. SETTING: Tertiary public hospital in Brazil. PARTICIPANTS: Men (N=20) after CABG were randomized to cardiopulmonary rehabilitation (n=10; age, 64+/-8y) or to usual care (n=10; age, 63+/-7y). INTERVENTIONS: Ten subjects underwent a 6-day postoperative in-hospital program, which included the use of expiratory positive airway pressure mask and bronchial hygiene techniques, coupled with progressive distance walking and calisthenics as well as cardiopulmonary training. Ten controls were followed by their own physicians and received routine nursing assistance but were not exposed to any specific respiratory or motor physical intervention. MAIN OUTCOME MEASURES: Maximal inspiratory and expiratory pressure were measured by a pressure transducer, and the highest pressure obtained in 6 measurements was used for analysis (before surgery, and 7 and 30d after surgery). The six-minute walk test (6MWT) was performed 7 days after surgery, and maximal cardiopulmonary exercise testing was performed 30 days after CABG. RESULTS: After randomization, clinical and functional characteristics were similar in the 2 groups. Rehabilitation resulted in maintenance of maximal inspiratory pressure (PImax) measured at 7 and 30 days postoperatively, respectively (from 68+/-19% at baseline to 58+/-22% and to 61+/-22% predicted), while it was significantly reduced in the control group. 6MWT distance was longer 7 days after CABG in rehabilitation subjects (416+/-78m) than controls (323+/-67m). Peak oxygen uptake (Vo(2)peak) at day 30 was also higher (28%) in the rehabilitation group and was correlated with PImax (r=.90). CONCLUSIONS: A 6-day rehabilitation program attenuated the postoperative reduction in respiratory muscle strength and also improved the recovery of functional capacity after CABG. The correlation between PImax and Vo(2)peak during the late postoperative period suggests that inspiratory muscle strength is an important determinant of functional capacity after CABG.

Inspiratory resistive loading after all-out exercise improves subsequent performance.

We have previously shown that post-exercise inspiratory resistive loading (IRL) reduces blood lactate ([Lac(b)(-)]). In this study, we tested the hypothesis that IRL during recovery could improve subsequent exercise performance. Eight healthy men underwent, on different days, two sequential 30-s, cycle ergometer Wingate tests. During the 10-min recovery period from test 1, subjects breathed freely or through an inspiratory resistance (15 cm H(2)O) with passive leg recovery. Arterialized [Lac(b)(-)] values, perceptual scores (Borg), cardiac output by impedance cardiography (QT), and changes in the deoxygenation status of the M. vastus lateralis by near-infrared spectroscopy (DeltaHHb), were recorded. [Lac(b)(-)] was significantly reduced after 4 min of recovery with IRL (peak [Lac(b)(-)] 12.5 +/- 2.3 mmol l(-1) with free-breathing vs. 9.8 +/- 1.5 mmol l(-1) with IRL). Effort perception was reduced during late recovery with IRL compared with free-breathing. Cardiac work was increased with IRL, since heart rate and QT were elevated during late recovery. Peripheral muscle reoxygenation, however, was significantly impaired with IRL, suggesting that post-exercise convective O(2) delivery to the lower limbs was reduced. Importantly, IRL had a dual effect on subsequent performance, i.e., improvement in peak and mean power, but increased fatigue index (P < 0.05). Our data demonstrate that IRL after a Wingate test reduces post-exercise effort perception and improves peak power on subsequent all-out maximal-intensity exercise.

Respiratory muscle function and exercise intolerance in heart failure.

Inspiratory muscle weakness (IMW) is prevalent in patients with chronic heart failure (CHF) caused by left ventricular systolic dysfunction, which contributes to reduced exercise capacity and the presence of dyspnea during daily activities. Inspiratory muscle strength (estimated by maximal inspiratory pressure) has independent prognostic value in CHF. Overall, the results of trials with inspiratory muscle training (IMT) indicate that this intervention improves exercise capacity and quality of life, particularly in patients with CHF and IMW. Some benefit from IMT may be accounted for by the attenuation of the inspiratory muscle metaboreflex. Moreover, IMT results in improved cardiovascular responses to exercise and to those obtained with standard aerobic training. These findings suggest that routine screening for IMW is advisable in patients with CHF, and specific IMT and/or aerobic training are of practical value in the management of these patients.

Blood lactate during recovery from intense exercise: impact of inspiratory loading.

PURPOSE: It has long been suggested that inspiratory muscle activity may impact blood lactate levels ([Lac(-)]B) during the recovery from dynamic exercise. In this study, we tested the hypothesis that inspiratory muscle activation during recovery from intense exercise would contribute to La clearance, thus leading to reduced [Lac(-)]B. METHODS: Twelve healthy men underwent two maximal, incremental exercise tests on different days. During a 20-min inactive recovery period, they breathed freely or against a fixed inspiratory resistance of 15 cm H2O. During recovery, pulmonary gas exchange was continuously monitored, and serial samples of arterialized venous blood were obtained for [Lac(-)]B, pH, PCO2, and HCO3(-). RESULTS: Subjects presented similar ventilatory and gas-exchange responses at peak exercise during both experimental conditions. [Lac(-)]B during recovery was reduced with inspiratory resistance (7.7 +/- 1 vs 10.4 +/- 1, 7.8 +/- 2 vs 10.3 +/- 2, and 7.3 +/- 1 vs 9.7 +/- 2 mM at 5, 7, and 9 min of recovery, respectively; P < 0.05), but no differences were found for blood acid-base status. Inspiratory resistance was associated with increased metabolic demand (V O2 and V CO2) but improved ventilatory efficiency, with lower V E/[V CO2] and increased alveolar ventilation. CONCLUSION: These data are consistent with the notion that inspiratory muscles may be net consumers of lactate during recovery from intense exercise.

Attenuation of muscle metaboreflex in chronic obstructive pulmonary disease.

PURPOSE: Abnormal skeletal muscle function is well documented in chronic obstructive pulmonary disease, but there is no information about the activity of muscle metabosensitive afferents. In this study, we tested the hypothesis that patients with chronic obstructive pulmonary disease would have abnormal reflex responses to stimulation of metabosensitive afferents in skeletal muscle when compared with healthy, matched subjects. METHODS: In 16 patients with moderate to severe chronic obstructive pulmonary disease and 13 healthy, age-matched control subjects, we evaluated heart rate, mean blood pressure, calf blood flow, and calf vascular resistance responses to static handgrip exercise at 30% of maximal voluntary contraction, followed by recovery with or without circulatory occlusion. Muscle metaboreflex control of calf vascular resistance was estimated by subtracting the area under the curve with circulatory occlusion from the area under the curve without circulatory occlusion. RESULTS: Mean blood pressure and heart rate responses were not significantly different in patients and controls during exercise and recovery. In the control group, calf vascular resistance increased significantly during exercise and remained elevated above baseline during circulatory occlusion, whereas in patients changes from rest were not significantly different in both trials. Estimated muscle metaboreflex control of calf vascular resistance was significantly reduced in the patients (controls: 31 +/- 22 units, patients: 8 +/- 31 units, P < 0.05). CONCLUSION: Patients with chronic obstructive pulmonary disease have a reduced calf vascular resistance response to handgrip exercise and to selective activation of muscle metaboreflex when compared with healthy subjects.

Short-term folinic acid supplementation and aerobic exercise improve vascular reactivity in HIV-infected individuals.

The aim of this study was to determine the effect of supervised exercise and folinic acid supplementation on endothelial function in HIV-infected individuals. A randomized clinical trial, double blinded, was conducted with 16 HIV-infected individuals, antiretroviral therapy (at least 6 months) with undetectable viral load (<50 copies/mL), and CD4 count > 200 cells/mm3. The subjects were randomized to aerobic exercise (n = 5) and daily intake for 4 weeks of 5 mg of folinic acid (n = 6) or placebo (n = 5) groups. To assess endothelial function, venous occlusion plethysmography in the brachial artery by the protocol of reactive hyperemia was performed. The aerobic protocol consisted in cycling exercise, 3 times/week at 60-80% VO2max, for 4 weeks. Exercise group (Δ6.5 mL/min/100 mL) and folinic acid group (Δ7.3 mL/min/100 mL) improved reactive hyperemia, but no difference was found in placebo group (from Δ -0.3 ml/min/100 ml, time p < 0.001, interaction p = 0.02). Results demonstrate that supervised exercise and folinic acid supplementation in very short term improve endothelial function in HIV-infected individuals. As exercise and folate supplementation are safe and relatively inexpensive, this finding deserves more attention in large randomized clinical trials in an attempt to reduce cardiovascular risk in HIV-infected population.

Trimetazidine added to combined hemodynamic antianginal therapy in patients with type 2 diabetes: a randomized crossover trial.

BACKGROUND: In nondiabetic patients with stable angina, combined treatment with hemodynamic agents and trimetazidine is well-tolerated and effective in controlling ischemia. This study aims to evaluate the antiischemic and metabolic effects of trimetazidine in patients with type 2 diabetes mellitus, not eligible for revascularization, who remained symptomatic despite the use of at least 2 antianginal agents. METHODS: A randomized, double-blind, crossover clinical trial was used. Ten patients were randomized to receive trimetazidine (20 mg, 3 times a day) or placebo for 6-week periods. At baseline and at the end of each 6-week intervention period, clinical and biochemical evaluations, exercise testing, 24-hour ambulatory blood pressure, and Holter monitoring were performed. RESULTS: During trimetazidine therapy, patients had significant improvement on angina functional class (P < .05), with decrease in the number of weekly angina episodes (1.5 +/- 0.8 vs 0.4 +/- 0.7, P < .01), and in sublingual nitrate doses (1.4 +/- 0.7 mg vs 0.1 +/- 0.3 mg, P < .001). Time to 1-mm ST-segment depression during exercise test was increased after trimetazidine use (229 +/- 126 seconds at baseline, 276 +/- 101 seconds after placebo, and 348 +/- 145 seconds after trimetazidine, P < .001). No differences were observed between treatment periods on mean 24-hour blood pressure, heart rate, and rate-pressure product evaluated concomitantly with ambulatory blood pressure and Holter monitoring. Glycemic and lipid profiles were similar after trimetazidine and placebo use. CONCLUSIONS: In patients with diabetes who remain symptomatic, the addition of trimetazidine improves symptoms and exercise responses without hemodynamic or metabolic changes. The present data suggest that trimetazidine may be an effective adjunct therapy for these patients, but further investigation is needed to confirm these findings.