Correlation between coronary microvascular function and angina status in patients with stable microvascular angina.

BACKGROUND: Classical anti-ischemic drugs are the first-line form of treatment in patients with microvascular angina (MVA), but they often fail to achieve a satisfactory control of angina symptoms. It is unknown whether there is any relation between improvement of angina status and changes in microvascular function induced by classical anti-ischemic drugs in MVA patients. AIM: To assess whether, in MVA patients, the effects of classical anti-ischemic drugs on symptoms and quality of life (QoL) are related to changes in coronary microvascular function. PATIENTS AND METHODS: We studied 51 patients (59±10 years; 15 men) with MVA. Coronary blood flow (CBF) response to adenosine (ADO) and to cold pressor test (CPT), Seattle Angina Questionnaire (SAQ) and EuroQoL scale were assessed at baseline, in pharmacological washout, and after 12 months under anti-ischemic therapy. Patients were divided into 2 groups: (1) Group 1 included patients with no improvement of QoL (EuroQoL score change < 10 points); (2) Group 2 included patients with QoL improvement (increase in EuroQoL score ≥ 10 points). RESULTS: At baseline, the 2 groups were similar in age, gender, cardiovascular risk factors, CBF response to ADO and to CPT, SAQ and EuroQoL scores. At follow-up the 2 groups differed only for beta blockers use (27% vs. 88% in group 1 and 2, respectively; p < 0.001). A significant improvement in SAQ score was observed only in group 2. CBF response to both ADO and CPT showed a similar improvement in the 2 groups. No relation was found between changes in coronary microvascular function and in angina status. CONCLUSIONS: In MVA patients beta-blockers are more effective than other anti-ischemic drugs in improving angina symptoms. The improvement of angina status does not seem to be mediated by changes in coronary microvascular function.

Metformin improves endothelial function in type 1 diabetic subjects: a pilot, placebo-controlled randomized study.

AIMS: Several studies have investigated the effects of metformin treatment in patients with type 1 diabetes mellitus (T1DM). No study has hitherto examined its effects on endothelial function in these patients. In this study we sought to evaluate the effect of metformin on endothelial function in type 1 diabetic patients. METHODS: Forty-two uncomplicated T1DM patients were randomized in a placebo-controlled, double-blind, 6-month trial to treatment with either metformin or placebo. Glycometabolic and clinical parameters as well as flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) of the right brachial artery were measured at baseline and at the end of the study. Glycaemic variability (GV, calculated from continuous glucose monitoring data) and a biomarker of oxidative stress [urinary 8-iso-prostaglandin F2α (PGF2α)] were also assessed. RESULTS: Baseline data were similar in the two groups. Compared with placebo, metformin significantly reduced body weight [-2.27 kg (95% confidence interval: -3.99; -0.54); p = 0.012] whilst improved FMD [1.32% (0.30; 2.43); p = 0.013] and increased PGF2α [149 pg/mg creatinine (50; 248); p = 0.004]. Notably, the improvement of FMD did not correlate with the decrease of body weight (r(2) < 1%). NMD, haemoglobin A1c, GV, daily insulin dose and other parameters did not significantly change after the treatment comparing the two groups. CONCLUSIONS: Our pilot trial showed that, in uncomplicated type 1 diabetic subjects, metformin improved FMD and increased PGF2α, a marker of oxidative stress, irrespective of its effects on glycaemic control and body weight. Randomized, blinded clinical trials are needed to evaluate the benefits and risks of metformin added to insulin in type 1 diabetes.

Effect of bariatric surgery on peripheral flow-mediated dilation and coronary microvascular function.

BACKGROUND AND AIMS: To assess the effects of bariatric surgery (BS) on peripheral endothelial function and on coronary microvascular dilator function. METHODS AND RESULTS: We studied 50 morbidly obese patients (age 38 ± 9, 13 M) who underwent BS and 20 comparable obese controls (age 41 ± 11, 6 M) without any evidence of cardiovascular disease. Peripheral vascular dilator function was assessed by brachial artery diameter changes in response to post-ischemic forearm hyperaemia (flow-mediated dilation, FMD). Coronary microvascular function was assessed by measuring coronary blood flow (CBF) velocity response to i.v. adenosine and to cold pressor test (CPT) in the left anterior descending coronary artery by transthoracic Doppler echocardiography. The tests were performed at baseline and at 3-month follow-up. At baseline, FMD and CBF response to adenosine and CPT were similar in the 2 groups. Compared to baseline, FMD at follow-up improved significantly in BS patients (5.9 ± 2.7% to 8.8 ± 2.4%, p < 0.01), but not in controls (6.3 ± 3.2% vs. 6.4 ± 3.1%, p = 0.41). Similarly, a significant improvement of CBF response to adenosine (1.63 ± 0.47 to 2.45 ± 0.57, p < 0.01) and to CPT (1.43 ± 0.26 to 2.13 ± 0.55, p < 0.01) was observed in BS patients but not in controls (1.55 ± 0.38 vs. 1.53 ± 0.37, p = 0.85; and 1.37 ± 0.26 vs. 1.34 ± 0.21, p = 0.48, respectively). The favourable vascular effects of BS were similar independently of the presence and changes of other known cardiovascular risk factors and of basal values and changes of serum C-reactive protein levels. CONCLUSIONS: Our data show that, in morbidly obese patients, together with peripheral endothelial function, BS also improves coronary microvascular function. These effects suggest global improvement of vascular function which can contribute significantly to the reduction of cardiovascular risk by BS reported in previous studies.

Low glucose blood levels are associated with abnormal cardiac sympatho-vagal balance in type 2 diabetic patients with coronary artery disease.

BACKGROUND AND OBJECTIVES: Glycemic control has been suggested to improve prognosis in diabetic patients, but recent trials failed to show benefits from intensive glycemic control. Hypoglycaemic episodes or large variability in glucose blood levels causing a sympatho-vagal imbalance of cardiac autonomic function (CAF) might play a role in this result. In our study we assessed whether blood glucose fluctuation may be related to variations in CAF during daily life in diabetic patients with coronary artery disease (CAD). MATERIALS AND METHODS: Twelve patients with type 2 diabetes mellitus with CAD (65+/-4 years, 2 women) underwent simultaneous 48-hour ECG Holter monitoring and continuous interstitial glucose measurements. The highest and lowest glucose levels for each 3-hour segments of the day were identified and heart rate variability (HRV) parameters were measured on Holter recordings on 5-minute intervals centred on these times. RESULTS: Overall, 294 glucose levels were available for analysis. In the whole population several HRV indices were significantly lower in correspondence of the lowest glucose blood levels and this difference was much more evident in patients who were not taking beta-blockers, than in patients who were taking beta-blockers. A significant, although mild, correlation was found between glucose blood levels and several time-and frequency domain HRV variables in patients not taking beta-blockers, but not in these on beta-blockers therapy. DISCUSSION: Our data suggest that, in type 2 diabetic patients with CAD, hypoglycaemic episodes are associated with depressed HRV and that beta-blocking agents are able to contrast this relation. These interesting results merit to be investigated in a larger population of patients.

Cardiac adrenergic nerve function and microvascular dysfunction in patients with cardiac syndrome X.

OBJECTIVE: To assess whether abnormalities in cardiac uptake of (123)I-metaiodobenzylguanidine (MIBG) correlate with coronary microvascular dysfunction in patients with cardiac syndrome X (CSX). SETTING: University hospital. PATIENTS: 29 patients (aged 59 (SD 7) years, 11 men) with typical CSX and a matched group of 20 healthy subjects (aged 56 (7) years, 8 men) were studied. INTERVENTIONS: Planar and single photon emission computed tomography (SPECT) MIBG myocardial scintigraphy was performed in all subjects. Coronary flow response (CFR) to adenosine and to cold pressor test (CPT) in the left anterior descending (LAD) coronary artery was assessed in all CSX patients and in 12 controls by transthoracic Doppler echocardiography. MAIN OUTCOME MEASURES: Abnormalities in cardiac MIBG scintigraphy were observed in 25 CSX patients (86.2%), but in no healthy control (p<0.001). Compared to controls, CSX patients showed a lower heart/mediastinum (H/M) ratio of MIBG uptake (1.69 (0.24) vs 2.2 (0.3), p<0.001) and a higher cardiac MIBG defect score (25 (22) vs 4 (2), p = 0.002). Both CFR to adenosine (3.31 (1.1) vs 1.94 (0.6), p<0.001) and CFR to CPT (2.35 (0.5) vs 1.63 (0.4), p<0.001) were lower in CSX patients than in controls. In CSX patients, however, no correlation was found between MIBG H/M ratio and CFR to adenosine (r = 0.17; p = 0.38) and to CPT (r = -0.28; p = 0.13), as well as between MIBG uptake score in the LAD territory and CFR to adenosine (r = 0.14; p = 0.47) and to CPT (r = 0.06; p = 0.73). CONCLUSION: Our data show striking abnormalities in cardiac adrenergic nerve function and in coronary microvascular function in CSX patients. However, no significant relation between the two abnormalities was found. Further studies are needed to clarify the mechanisms and the role of MIBG defects in CSX patients.