Cardiac sympathetic activity is associated with inflammation and neurohumoral activation in patients with idiopathic dilated cardiomyopathy

Background: Idiopathic dilated cardiomyopathy (IDC) is characterized by sympathetic nervous overactivity, inflammation and neurohumoral activation; however, their interrelationships are poorly understood. Methods and results: We studied 99 patients with IDC (age 54 ± 1 years, left ventricular ejection fraction (EF) 40 ± 1%, maximum oxygen uptake (VO₂max) 20 ± 1 ml kg^?1 min^?2, mean ± SEM) by using ¹²³I‐metaiodobenzylguanidine (MIBG) imaging. MIBG washout and MIBG heart/mediastinum (H/M)‐ratio at 4 h postinjection were calculated. In addition, the plasma levels of interleukin (IL)‐6 and N‐terminal B‐type natriuretic peptide (NT‐proBNP) were measured. MIBG washout and MIBG H/M ratio had a significant correlation with IL‐6 (r = 0·42, P<0·001 and r = ?0·31, P<0·01) and NT‐proBNP (r = 0·48, P<0·001 and r = ?0·40, P<0·001). During a median follow‐up of 4·1 years, 20 patients (20%) had an adverse cardiac event (death, heart transplantation or application of biventricular pacemaker or implantable cardioverter–defibrillator). In these patients, MIBG washout was higher (53 ± 4 versus 40 ± 2%, P = 0·01) and H/M ratio lower (1·38 ± 0·04 versus 1·51 ± 0·02, P = 0·01) than in patients without an event. Conclusions: In dilated cardiomyopathy, myocardial sympathetic innervation and activity are related to inflammation and neurohumoral activation. These relationships are at least partly independent of left ventricular function and exercise capacity.     

Elevated VEGF-plasma levels in young patients with mild essential hypertension

Background Growing evidence shows that inflammation plays a pivotal role in the pathophysiology of essential hypertension (EH). Vascular endothelial cell growth factor (VEGF) is currently discussed as a possible mediator of inflammation. To investigate the hypothesis that VEGF plays a role as an inflammatory mediator in EH we performed the present pilot study of young patients in a very early stage of EH. Materials and methods 15 young patients with mild EH [33·8 ± 7·3 years, systolic blood pressure (SBP): 143·8 ± 10·5 mmHg, diastolic blood pressure (DBP): 88·2 ± 11·1 mmHg, mean arterial pressure (MAP) 106·6 ± 10·4 mmHg] and 15 healthy controls (31·7 ± 10·6 years) were examined. Blood was drawn from a peripheral vein and serum levels of VEGF, monocyte‐chemoattractant‐protein (MCP)‐1, high‐sensitivity C‐reactive protein (hsCRP), interleukin (IL)‐6, and tumour‐necrosis‐factor (TNF)‐α were measured via commercially available enzyme‐linked immunoassays. Results Hypertensives showed increased plasma levels of VEGF (P < 0·05) and MCP‐1 (P < 0·05). VEGF positively correlated with MAP (r = 0·46, P < 0·05) and MCP‐1 (r = 0·63, P < 0·01). Multivariate analysis demonstrated VEGF to be an independent predictor of MCP‐1 levels. Furthermore, hypertensives had higher levels of hsCRP (P < 0·01), IL‐6 (P < 0·001) and TNF‐α (P < 0·05). IL‐6 levels correlated with SBP (r = 0·59, P < 0·001), DBP (r = 0·67, P < 0·001) and MAP (r = 0·46, P < 0·001). A significant positive correlation was also found between hsCRP levels and SBP (r = 0·39, P < 0·05). Conclusions This pilot study demonstrates that in an early state of EH, inflammatory pathways have already been activated. Besides classical pro‐inflammatory cytokines, VEGF serum levels are significantly elevated. The positive correlation of VEGF with MCP‐1 is suggestive for the already described induction of MCP‐1 via VEGF.     

Utility of ultrasound for body fat assessment: validity and reliability compared to a multicompartment criterion

Measurement of body composition to assess health risk and prevention is expanding. Accurate portable techniques are needed to facilitate use in clinical settings. This study evaluated the accuracy and repeatability of a portable ultrasound (US) in comparison with a four‐compartment criterion for per cent body fat (%Fat) in overweight/obese adults. Fifty‐one participants (mean ± SD; age: 37·2 ± 11·3 years; BMI: 31·6 ± 5·2 kg m^?2) were measured for %Fat using US (GE Logiq‐e) and skinfolds. A subset of 36 participants completed a second day of the same measurements, to determine reliability. US and skinfold %Fat were calculated using the seven‐site Jackson–Pollock equation. The Wang 4C model was used as the criterion method for %Fat. Compared to a gold standard criterion, US %Fat (36·4 ± 11·8%; P = 0·001; standard error of estimate [SEE] = 3·5%) was significantly higher than the criterion (33·0 ± 8·0%), but not different than skinfolds (35·3 ± 5·9%; P = 0·836; SEE = 4·5%). US resulted in good reliability, with no significant differences from Day 1 (39·95 ± 15·37%) to Day 2 (40·01 ± 15·42%). Relative consistency was 0·96, and standard error of measure was 0·94%. Although US overpredicted %Fat compared to the criterion, a moderate SEE for US is suggestive of a practical assessment tool in overweight individuals. %Fat differences reported from these field‐based techniques are less than reported by other single‐measurement laboratory methods and therefore may have utility in a clinical setting. This technique may also accurately track changes.     

Effects of hypocaloric very‐low‐carbohydrate diet vs. Mediterranean diet on endothelial function in obese women*

Background Obesity is a cardiovascular risk factor associated with endothelial dysfunction, but the effect of different weight loss strategies on endothelial function is not known. The effect of diet on endothelial function in two hypocaloric diets, a very‐low‐carbohydrate diet (A) and a Mediterranean diet (M), was measured by brachial artery flow‐mediated dilation (FMD). Design Using a longitudinal, randomized, open study design, subjects were engaged in a 2‐month weight loss diet. FMD, inflammatory cytokines [interleukin‐6 (IL‐6) and tumour necrosis factor‐α] and a marker of oxidative stress [8‐iso‐prostaglandin F2α (8‐iso‐PGF2α)] were measured in subjects on three occasions: before initiating the diet (T0), after 5–7 days of dieting (T5) and after 2 months of dieting (T60). The very short‐ and medium‐term time points were established to discriminate respectively the effect of the diet itself (T5) from that of weight loss (T60). Twenty overweight/obese but otherwise healthy women (BMI: 27–34·9 kg m^?2; age 30–50 years) completed the study. Results Group A lost more weight (mean ± SEM; ?7·6 ± 0·8 kg) than group M (?4·9 ± 0·6 kg, P = 0·014) at T60. The FMD was not significantly different between the two groups at T0 (group A: 12·2 ± 2·9% vs. group B: 10·3 ± 2·3%, P = ns). In group A, FMD was significantly reduced at T5 and returned to baseline at T60; in group M, FMD increased at T5 and returned to baseline at T60 (P = 0·007 for diet × time interaction). Serum concentrations of IL‐6 and 8‐iso‐PGF2α were not significantly different between the two groups at T0 and increased significantly at T5 only in group A (P < 0·001 and P < 0·005 respectively). Conclusion As endothelial dysfunction is known to be associated with acute cardiovascular events, this study suggests that the cardiovascular risk might be increased in the first days of a very‐low‐carbohydrate diet.     

Improvement of glycaemic control by nateglinide decreases systolic blood pressure in drug-naive patients with type 2 diabetes

Background It has been speculated that oral hypoglycaemic agents that block K‐ATP channels could potentially increase blood pressure by blocking such channels in vascular myocytes. No information about this issue exists regarding nateglinide. Design A multicentre, double‐blind, placebo‐controlled, randomized trial was conducted in 109 drug‐naive 30‐ to 75‐year‐old patients with type 2 diabetes and < 5 years of diabetes diagnosis, who are not taking antihypertensive drugs. These patients were assigned to receive placebo or fixed doses of nateglinide (120 mg before each main meal: breakfast, lunch and dinner) and evaluated at weeks 0 and 12 for (i) body mass index and blood pressure; (ii) standard laboratory tests, including haemoglobin A1c (HbA1c) and fasting plasma glucose; and (iii) incremental area under the curve for glucose and C‐peptide after a standardized liquid breakfast challenge, homeostasis model assessment (HOMA)‐B% (as surrogate of β‐cell activity) and HOMA‐S% (as surrogate of insulin sensitivity). Results At the end of the follow‐up period, patients in the nateglinide group (n = 55), compared to patients in the placebo group (n = 54), showed lower values of HbA1c (6·7 ± 0·6 vs. 7·2 ± 0·7%, respectively; P < 0·001), fasting plasma glucose (7·9 ± 2·1 vs. 8·5 ± 2·0 mmol L^?1; P = 0·023) and systolic blood pressure (125·3 ± 15·4 vs. 129·3 ± 18·7 mmHg; P = 0·015), and higher values of HOMA‐B%[75·7 (51·8–99·4) vs. 57·7 (42·2–83·4); P = 0·033]. A positive correlation was found between changes in HbA1c and systolic blood pressure in the nateglinide group (r = 0·355, P = 0·011). Conclusions In drug‐naive patients with type 2 diabetes, the improvement in glycaemic control with nateglinide is associated with a decrease in systolic blood pressure.     

Effect of polymerized-type I collagen in knee osteoarthritis. II. In vivo study

Background Polymerized‐Type I Collagen (Polymerized‐Collagen) is an anti‐inflammatory and a tissue regenerator biodrug. The aim of the study was to evaluate the efficacy and safety of intra‐articular injections of Polymerized‐Collagen in patients with knee osteoarthritis (OA). Methods and design Patients (n = 53) were treated with 12 intra‐articular injections of 2 mL of Polymerized‐Collagen (n = 27) or 2 mL of placebo (n = 26) during 6 months. Follow up period was 6 months. The primary endpoints included Western Ontario and McMaster University Osteoarthritis Index, Lequesne index, and pain intensity on a visual analogue scale (VAS). Secondary outcomes were patient global score, investigator global score and drug evaluation. Clinical improvement was determined if the decrease in pain exceeds 20 mm on a VAS and patients achieved at least 20% of improvement from baseline. Urinary levels of C‐terminal crosslinking telopeptide of collagen type II (CTXII) and serum high‐sensitivity C‐reactive protein (hsCRP) were determined by enzyme immunoassays. Statistical analysis was performed by intention to treat. Results Polymerized‐Collagen was safe and well tolerated. Patients had a statistically significant improvement (P < 0·05) from baseline vs. Polymerized‐Collagen and vs. placebo at 6 months in: Lequesne Index (13·1 ± 0·5 vs. 7·1 ± 0·7 vs. 9·6 ± 0·8; P = 0·027), WOMAC (9·0 ± 0·5 vs. 4·0 ± 0·6 vs. 5·80 ± 0·8; P = 0·032), patient VAS (60·0 ± 2·6 vs. 20·6 ± 2·4 vs. 36·1 ± 4·5; P = 0·003), physician VAS (49·8 ± 1·9 vs. 16·8 ± 2·9 vs. 29·8 ± 2·9; P = 0·002), patient global score (1·08 ± 0·1 vs. 2·7 ± 0·1 vs. 1·9 ± 0·2; P = 0·028) and analgesic usage (30·1 ± 9·4 vs. 11·0 ± 3·4 vs. 17·9 ± 4·9; P = 0·001). This improvement was persistent during the follow up. A threefold increase in CTXII was determined in placebo group. No differences were found on hs CRP and incidence of adverse events between groups. Conclusion Polymerized‐Collagen is safe and effective in the treatment of knee OA.     

Elevation of matrix metalloproteinases and interleukin-6 in the culprit coronary artery of myocardial infarction

Background Interleukin‐6 (IL‐6) and metalloproteinases (MMPs) are involved in the instability of vulnerable plaque associated with the induction of acute myocardial infarction (AMI). We examined the regional changes of cytokines, MMPs and adhesion molecules in patients with AMI to elucidate how these factors are involved in the onset of AMI. Materials and methods One hundred and twenty‐two patients with AMI were included. Blood was aspirated from the culprit coronary artery with a thrombectomy catheter, and was also sampled from peripheral veins during the coronary intervention. Control samples were obtained from the peripheral blood of age‐matched patients. Results The serum levels of IL‐6 (P < 0·05), tumour necrosis factor‐α (P < 0·005), MMP‐1 (P < 0·001), MMP‐13 (P < 0·001), soluble intercellular adhesion molecule‐1 (P < 0·005), and soluble vascular cellular adhesion molecule‐1 (P < 0·05) in peripheral blood were significantly higher in the AMI group than in the controls. Aspirated serum contained significantly higher levels of IL‐6 (P < 0·001), MMP‐1 (P < 0·001), and MMP‐13 (P < 0·05) compared to the peripheral blood of AMI. Serum IL‐6 levels were significantly higher in the aspirated than in the peripheral blood in the patients hospitalized within 6 h and 6–12 h, but were similar in the aspirated and peripheral blood of the patients hospitalized 12–24 h after the onset of AMI. There were no differences between the aspirated serum and peripheral blood in the levels of interleukin‐1β and MMP‐2. Conclusions The levels of MMP‐1, MMP‐13 and IL‐6 were higher in the culprit coronary artery than in the peripheral blood. These factors appear to be involved in the early stage of AMI.     

Serum sialic acid changes in type 2 diabetic patients on metformin or rosiglitazone treatment

What is known and objective: Serum sialic acid is a recently investigated potential risk‐marker for cardiovascular complications. There is a known association between sialic acid and cardiovascular complications in diabetes mellitus. We aimed to investigate the effect of antidiabetic drugs on the serum concentration of sialic acid. Methods: We investigated the effect of metformin and rosiglitazone on the concentration of sialic acid in 120 type 2 diabetic patients, divided into a group (n = 60) receiving metformin and a group (n = 60) receiving rosiglitazone treatment. Results: Serum sialic acid was significantly higher in patients on rosiglitazone (66·90 ±8·80 mg/dL vs. 57·6 ± 8·46 mg/dL, P <0·01) and metformin (61·95 ± 10·49 mg/dL vs. 57·6 ±8·46mg/dL, P < 0·04) when compared with control subjects. In addition, rosiglitazone‐treated patients showed a significant increase in cardiovascular risk factors, notably total cholesterol (246·45 ± 20·2 mg/dL vs. 170·6 ± 15·1 mg/dL, P =0·01), triglyceride (178 ± 9·20 mg/dL vs. 149·35 ±6·31 mg/dL, P < 0·04) and glycohemoglobin (HbA1‐c) concentration (8·17 ± 1·43% vs. 4·38 ±0·96%, P < 0·02) compared with normal control subjects. The patients on metformin also showed significantly higher levels of serum glucose (133·7 ± 9·63 mg/dL vs. 88·35 ± 6·31 mg/dL, P <0·04) and glycohemoglobin (HbA1‐c) (8·23 ±1·75% vs. 4·38 ± 0·96%, P < 0·02) when compared with control subjects. Comparison of the two groups of patients revealed a significantly higher serum sialic acid (66·90 ± 8·80 mg/dL vs. 61·95 ±10·49 mg/dL, P < 0·05), total cholesterol (246·45 ±20·2 mg/dL vs. 192 ± 14·23 mg/dL, P <0·02) and triglyceride (178 ± 9·20 mg/dL vs. 158 ± 14·51mg/dL, P < 0·05) concentrations in the rosiglitazone‐treated patients. What is new and conclusions: This study suggests significantly higher levels of serum sialic acid and other cardiovascular risk factors in rosiglitazone‐treated patients than in metformin‐treated patients. The lower sialic acid concentration may explain a better metformin antidiabetic effect than with rosiglitazone.     

Leptospirosis-associated acute kidney injury: penicillin at the late stage is still controversial

What is known and Objective: Some antimicrobial agents are active in vitro against Leptospiras. The use of penicillins at the late stage of leptospirosis is still controversial. We aimed to evaluate the use of penicillin in patients with leptospirosis‐associated acute kidney injury (AKI). Methods: A retrospective study was conducted of patients with leptospirosis admitted to two hospitals in Fortaleza city, Brazil, between 1985 and 2008. AKI was defined according to the RIFLE and AKIN classifications. Patients were divided in two groups according to whether they were treated with a penicillin or not. Results: Two hundred and eighty‐seven patients were included, with an average age of 36·8 ± 15·6 years and mostly male (80·8%). One hundred and twelve patients (39%) received a penicillin. Patients treated with a penicillin were younger (32 ± 14 years vs. 39 ± 16 years, P = 0·0002) and had a shorter hospital stay (8·4 ± 5·0 vs. 11 ± 7·7 days, P < 0·0001). There was no difference in the onset of symptoms before hospital admission between the two groups (6·5 ± 3·0 vs. 7·7 ± 4·7, P = 0·33). Systolic blood pressure was lower in the penicillin group (111 ± 21 vs. 119 ± 22 mmHg, P = 0·04). AKI, need of dialysis and renal recovery at the time of hospital discharge were more frequent in patients who did not use a penicillin (P < 0·05). Mortality was similar in both groups (11·6% vs. 13·7%, P = 0·60). Conclusion: Treatment of leptospirosis with antibiotics, including the penicillin, remains controversial. The main benefit of using penicillin in the present study was a reduction in the length of hospital stay and fewer complications, such as AKI, but its use was not associated with a decrease in mortality. On balance of risks and benefits, we recommend the use of penicillin in late‐stage leptospirosis.     

Maintained cerebral metabolic ratio during exercise in patients with β‐adrenergic blockade

Background: Decreased cerebral metabolic ratio (CMR) [molar uptake of O₂ versus molar uptake of (glucose + ½ lactate)] during exercise is attenuated by intravenous administration of the non‐selective β‐adrenergic receptor antagonist propranolol. We evaluated to what extent cirrhotic patients in oral treatment with propranolol are able to mobilize brain non‐oxidative carbohydrate metabolism. Methods: Incremental cycle ergometry to exhaustion (86 ± 4·2 W; mean ± SD) was performed in eight cirrhotic patients instrumented with a catheter in the brachial artery and one retrograde in the right internal jugular vein. Healthy subjects form the control group. Results: In β‐blocked cirrhotic patients arterial lactate increased from 1·5 ± 0·3 to 5·1 ± 0·8 mM (P<0·05) and the arterial–jugular venous difference (a–v diff) from ?0·01 ± 0·03 to 0·30 ± 0·05 mM (P<0·05) at rest and during exercise, respectively. During exercise the glucose a–v diff of 0·46 ± 0·06 mM remained at a level similar to rest (0·54 ± 0·03 mM) and at exhaustion the CMR was not significantly changed (5·8 ± 1·1 versus 6·0 ± 0·6). In controls, CMR decreased from 5·6 ± 0·9 at rest to 3·4 ± 0·7 (P<0·05) during maximal exercise and at a lactate level comparable to that achieved by the patients it was 3·8 ± 0·4. Conclusion: During exhaustive exercise in cirrhotic patients the CMR is maintained and a significant cerebral uptake of lactate is demonstrated. The data suggest that oral treatment with a non‐selective β‐adrenergic receptor antagonist attenuates cerebral non‐oxidative metabolism.     

Haemodynamic effects of patent foramen ovale and atrial septal defect closure: a comparison during percutaneous shunt closure

Objectives: We investigated the haemodynamic effect of percutaneous closure of an intra‐atrial shunt, using non‐invasive finger pressure measurements. Background: Percutaneous closure of both patent foramen ovale (PFO) and atrial septal defect (ASD) is widely practised. Currently no data are available on short‐term haemodynamic changes induced by closure. Methods: Twenty‐five consecutive patients (mean age 49 ± 17 years, 10 men) who underwent a percutaneous closure of a PFO (n = 15) or ASD (n = 10) were included in this study. During the procedure blood pressure and heart rate (HR) were monitored continuously with a Finometer^®. Changes in systolic, mean, and diastolic pressure, stroke volume (SV), cardiac output (CO) and total peripheral resistance (TPR) were computed from the pressure registrations using Modelflow^® methodology. Results: Baseline characteristics were similar for the PFO and ASD patients. After PFO closure none of the haemodynamic parameters changed significantly. After ASD closure the systolic, mean, and diastolic pressures increased 7·1 ± 5·4 (P = 0·003), 3·8 ± 3·5 (P = 0·007) and 2·0 ± 3·0 mmHg (P = ns) respectively. HR decreased 5·1 ± 5·3 beats per minute (P = 0·01). SV, CO and TPR increased 8·5 ± 6·4 ml (13·5%; P = 0·002), 0·21 ± 0·45 l min^?1 (5·6%; P = ns) and 0·02 ± 0·14 dynes (4·1%; P = ns) respectively. The changes in SV differ between the PFO and ASD patients (P = 0·009). Conclusions: Using non‐invasive finger pressure measurements, we found that SV, mean and systolic blood pressure increased immediately after percutaneous closure of an ASD in adults, whereas the percutaneous PFO closure had no effect on haemodynamic characteristics.     

High-density lipoprotein cholesterol, C-reactive protein, and prevalence and severity of coronary artery disease in 5641 consecutive patients undergoing coronary angiography

Background Although high‐density lipoprotein cholesterol (HDL‐C) and C‐reactive protein (CRP) are well‐established predictors for future cardiovascular events, little information is available regarding their correlation with the prevalence and severity of angiographically evaluated coronary artery disease (CAD). Material and methods Five thousand six hundred forty‐one consecutive patients undergoing coronary angiography for the evaluation of CAD were analysed. Cardiovascular risk factors were assessed by routine blood chemistry and questionnaire. CAD severity was graded by visual estimation of lumen diameter stenosis with significant stenoses defined as lumen diameter reduction of ≥ 70%. Coronary angiograms were graded as one‐, two‐ or three‐vessel disease, as nonsignificant CAD (lumen irregularities < 70%) or non‐CAD. Results HDL‐C (60·3 ± 18·5 vs. 51·9 ± 15·3 mg dL^?1; P < 0·001) was higher and CRP was lower (0·65 ± 1·68 vs. 1·02 ± 2·38 mg dL^?1; P < 0·001) in non‐CAD (n = 1517) compared to overall CAD patients (n = 4124). CAD patients were older (65·2 ± 10·5 years vs. 59·9 ± 11·4 years), more often diabetics (19·2% vs. 10·6%) and hypertensives (79·2% vs. 66·0%) and included more smokers (18·8% vs. 16·5%) (all P < 0·005). Low‐density lipoprotein cholesterol (124·5 ± 38·3 vs. 126·0 ± 36·3 mg dL^?1; P = NS) was similar in overall CAD and non‐CAD patients with more statin users (43·4% vs. 27·9%; P < 0·001) among CAD patients. Comparing non‐CAD with different CAD severities using analysis of variance, results did not change substantially. In a multivariate analysis, HDL‐C and CRP remained independently associated with the prevalence of CAD. In addition, HDL‐C is also a potent predictor for the severity of CAD. Conclusions In this large consecutive patient cohort, HDL‐C and CRP are independently associated with the prevalence of CAD. In this analysis, HDL‐C is an even stronger predictor for CAD than some other major classical risk factors.     

Spontaneous and bleomycin-induced chromosome damage in non cancer thyroid patients

Background Presence of chromosome damage in lymphocytes of patients affected by several diseases, including cancer, was detected by the micronucleus (MN) assay. Individual susceptibility to DNA damage, considered as a risk factor for cancer, can be also evaluated using the bleomycin (BLM) sensitivity test. Materials and methods We aimed to evaluate spontaneous or BLM‐induced MN frequencies in autoimmune (AI, n = 19) and non autoimmune (NAI, n = 11) thyroid patients, not receiving ¹³¹I radiometabolic therapy with respect to a control group of 18 healthy subjects. According to thyroid function, patients were also divided into hypothyroid (n = 10), euthyroid (n = 13) or hyperthyroid (n = 7) subjects. Results Spontaneous MN frequencies of AI and NAI patients did not differ from those of controls. Hypothyroid patients had more elevated MN basal levels (9·00 ± 1·71‰) than hyperthyroid (3·75 ± 1·17‰, P < 0·05) and euthyroid (5·38 ± 0·97‰, P < 0·01) patients or healthy subjects (4·17 ± 0·63‰, P < 0·01). In particular, the hypothyroid AI group showed the highest value (9·79 ± 2·26‰, P < 0·01). All thyroid patients responded differently to BLM than controls (39·90 ± 2·48‰ vs. 31·08 ± 2·51‰, P = 0·0377). The NAI group had BLM‐induced MN levels (45·00 ± 2·56‰) significantly higher (P = 0·0215) than AI patients (36·95 ± 3·49‰) or healthy subjects (31·08 ± 2·51‰). No significant difference was seen when patients were stratified according to autoimmunity. Conclusions We report that hypothyroid patients exhibit a moderate increase in the level of spontaneous genome damage, and that AI thyroid patients resulted to be less sensitive than NAI patients to the mutagen sensitivity test. In prospective, it may be of interest to reinvestigate hypothyroid patients when correction of their dysfunction is achieved.     

Severe obstructive sleep apnoea exacerbates the microvascular impairment in very mild hypertensives

Background Different studies have shown that obstructive sleep apnoea syndrome (OSAS), frequently associated with hypertension, represents a harmful and independent risk for cardiovascular diseases. The aim of our study was to ascertain whether the occurrence of OSAS could worsen microcirculatory impairment in very mild hypertensives. Materials and methods One hundred untreated very mild hypertensives underwent polysomnography and subdivided into 32 non‐OSAS, 33 mild OSAS and 35 severe OSAS patients on standardized criteria. They underwent routine blood chemistry, ambulatory blood pressure monitoring and anthropometric analysis. Skin capillary density (n mm^?2) of forearm (FAC) and periungueal (PUC) fields was obtained through videocapillaroscopy. By a venous congestion manoeuvre, PUC was maximized (CVC) and secondary capillary recruitment (GAIN) was calculated. These measurements served as indices of structural and functional capillary rarefaction, respectively. Results Severe OSAS hypertensives showed reduced FAC (P < 0·001) and PUC (P < 0·001) as compared to those with mild OSAS and non‐OSAS, but a greater CVC (P < 0·01) and GAIN (P < 0·001). Multiple regression analysis showed that PUC was inversely related to total sleep time with oxyhaemoglobin saturation at < 90% (TST90) (P < 0·001) and FAC to the apnoea‐hypopnoea index (AHI) (P < 0·001) and to the sleep propensity (P < 0·01). CVC was positively associated to AHI (P < 0·001) and GAIN to TST90 (P < 0·05). Conclusions The findings suggest that OSAS, by means of reduced basal and functional capillarity rarefaction, might pose an additional risk of impaired peripheral perfusion in very mild hypertensives. A microcirculation studytherefore should be a part of the clinical approach in patients at high cerebro‐cardiovascular risk such as hypertensives and patients with OSAS.     

Reduced cerebral oxygen–carbohydrate index during endotracheal intubation in vascular surgical patients

Brain activation reduces balance between cerebral consumption of oxygen versus carbohydrate as expressed by the so‐called cerebral oxygen‐carbohydrate‐index (OCI). We evaluated whether preparation for surgery, anaesthesia including tracheal intubation and surgery affect OCI. In patients undergoing aortic surgery, arterial to internal jugular venous (a‐v) concentration differences for oxygen versus lactate and glucose were determined from before anaesthesia to when the patient left the recovery room. Intravenous anaesthesia was supplemented with thoracic epidural anaesthesia for open aortic surgery (n = 5) and infiltration with bupivacaine for endovascular procedures (n = 14). The a‐v difference for O₂ decreased throughout anaesthesia and in the recovery room (1·6 ± 1·9 versus 3·2 ± 0·8 mmol l^?1, mean ± SD), and while a‐v glucose decreased during surgery and into the recovery (0·4 ± 0·2 versus 0·7 ± 0·2 mmol l^?1, P<0·05), a‐v lactate did not change significantly (0·03 ± 0·16 versus ?0·03 ± 0·09 mmol l^?1). Thus, OCI decreased from 5·2 ± 1·8 before induction of anaesthesia to 3·2 ± 1·0 following tracheal intubation (P<0·05) because of the decrease in a‐v O₂ with a recovery for OCI to 4·6 ± 1·4 during surgery and to 5·6 ± 1·7 in the recovery room. In conclusion, preparation for surgery and tracheal intubation decrease OCI that recovers during surgery under the influence of sensory blockade.     

Comparison of bioimpedance and radioisotope methods in the estimation of extracellular water volume before and after coronary artery bypass grafting operation

To estimate extracellular water volume (ECW) changes in connection with coronary artery bypass grafting operation, simultaneous ECW estimations by ⁵¹Cr‐EDTA dilution and whole‐body bioimpedance techniques were performed in 15 patients. The assessments of ECW were compared with patients’ weighing results. Whole‐body bioimpedance‐derived ECW correlated significantly with ⁵¹Cr‐EDTA dilution‐based ECW in the pre‐operative period (r=0·74; P<0·005); the bias was 0·2 ± 1·1 l (±SD). In the post‐operative period, the agreement between these methods was poor, the bias being 0·5 ± 2·5 l, and no significant correlation between the methods was found (r=0·38; P>0·05). Whole‐body bioimpedance‐derived ECW changes correlated significantly with weight changes of the patient induced by the operation (r=0·52; P<0·05). ⁵¹Cr‐EDTA dilution‐based ECW changes correlated neither with weight changes (r=0·33; P>0·05) nor with bioimpedance‐derived ECW changes (r=0·03; P>0·05). Alterations in radioisotope tracer distribution and loss of it due to blood leakage in the post‐operative period were presumed to explain the discrepancy between dilution technique and weighing results. The results suggest that bioimpedance is a useful non‐invasive method for assessment of extracellular volume changes induced by coronary artery bypass grafting operations. ⁵¹Cr‐EDTA dilution‐based ECW determination is not suitable in related conditions.     

Excessive exercise ventilation in moderate left heart dysfunction. Influence of postural changes in central haemodynamics and blood gases

To evaluate the relative importance of pulmonary congestion and peripheral hypoxia as causes for the excessive exercise ventilation in left heart dysfunction, seven patients with excessive ventilation and distinct left heart dysfunction during moderate exercise (LHD), and seven control patients with essentially normal exertional functions (CTR), had ventilation, central haemodynamics, arterial and mixed venous blood gases examined at rest and exercise, 32 W (25–40) in the LHD group and 44 W (33–49) in the CTR group, in lying and sitting positions. Change from lying to sitting exercise, led to fall in pulmonary artery wedge pressure (PAWP) from 31·0 ± 5·5 to 8·8 ± 5·0 mmHg in the LHD group, compared with from 13·7 ± 1·0 to 2·1 ± 2·4 mmHg in the controls, while ventilation/O₂ intake ratio (V˙/V˙O₂) and physiological dead space/tidal volume ratio (V_D/V_T) showed a tendency to rise, from 36·3 ± 8·8 to 39·2 ± 7·4, and from 0·35 ± 0·11 to 0·39 ± 0·09, respectively, in the LHD group, and from 27·5 ± 3·1 to 28·7 ± 5·3, and from 0·19 ± 0·09 to 0·21 ± 0·12 in the controls. Mixed venous O₂ tension (PvO ₂) showed a marked decline from 3·60 ± 0·33 to 3·26 ± 0·36 kPa in the LHD group, as compared with from 3·94 ± 0·28 to 3·71 ± 0·29 kPa in the controls, while the calculated physiologic shunt (Q˙_s/Q˙_t) suggested improved alveolo‐arterial gas exchange. The data fit in with recent studies ascribing the excessive exercise ventilation to a combination of signals from hypoxia‐induced changes, particularly in the exercising muscles, and augmented ergoreflex and central and peripheral chemoreceptor activity, partly to changes in the integrated control of ventilation and circulation, not to mechanisms related to pulmonary congestion.     

Effect of renal denervation on coronary flow reserve in patients with resistant hypertension

Renal denervation (RDN) is a potential modality in the treatment of patients with resistant hypertension (RH) and has shown beneficial effect on a variety of cardiovascular surrogate markers. Coronary flow reserve, as assessed by transthoracic Doppler echocardiography (TDE‐CFR) is impaired in patients with hypertension and is an independent predictor of cardiac morbidity. However, data on the effect of RDN on TDE‐CFR are scarce. The main objective of this study was to assess the effect of RDN on TDE‐CFR. Twenty‐six consecutive patients with RH (9 female and 17 male; mean age 62 ± 8 years; mean number of antihypertensive drugs 4·2 ± 1·6) underwent bilateral RDN. CFR was assessed at baseline and 6 months after intervention. Mean flow velocity was measured in the left anterior descending artery by transthoracic Doppler echocardiography at baseline and during adenosine infusion (TDE‐CFR). Systolic office blood pressure was reduced at follow‐up (174 ± 24 versus 162 ± 27 mmHG; P = 0·01). Mean systolic ambulatory blood pressure decreased from 151 ± 21 to 147 ± 18 (P = 0·17). TDE‐CFR remained unchanged 6 months after intervention (2·7 ± 0·6 versus 2·7 ± 0·7; P = 0·67). In conclusion, renal denervation was not associated with any changes in regard to coronary flow reserve at 6‐month follow‐up.     

Clinical impact of a pharmacist–physician co-managed programme on hyperlipidaemia management in Hong Kong

Objective: The study aimed to investigate the clinical impact of pharmacist–physician co‐managed programme on the management of hyperlipidaemia. Methods: The study was a prospective randomized controlled trial. Adult patients were selected if: (i) they were taking one or more lipid‐lowering agents with a valid lipid panel before their next follow up; (ii) had a baseline lipid profile within the previous 6 months; (iii) their lipid panel did not reach the targeted low‐density lipoprotein‐cholesterol (LDL‐C) goal based on the National Cholesterol Education Programme Adult Treatment Panel III. Pharmacists interviewed patients in the intervention group for 15–30 min to provide consultation on the drug regimen and lifestyle modifications. A telephone follow‐up every 4 weeks and a follow‐up interview on the date of the physician visit were scheduled. Patients in the control group received routine conventional care. The primary outcome measurement was the change in lipid panel between baseline and at the end of study. Results: One hundred and eighteen patients were recruited to the study [58 patients in intervention group (mean age 63 ± 10 years old) and 60 in control group (mean age 61 ± 12 years old)]. Starting with similar baseline levels, the end of study LDL‐C and total cholesterol levels for the intervention and control groups were LDL‐C: 2·80 ± 0·89 mmol/L and total cholesterol 4·75 ± 1·08 mmol/L vs. LDL‐C: 3·24 ± 0·78 mmol/L and total cholesterol 5·18 ± 0·93 mmol/L, respectively. The differences were statistically significant (P < 0·0015). Conclusion: The study showed that a pharmacist–physician co‐managed programme for hyperlipidaemic patient was effective in getting more patients to reach their target lipid levels.     

Postprandial impairment of resistance vessel function in insulin treated patients with diabetes mellitus type‐2

Reduced postischaemic reactive hyperaemia, is considered a marker of impaired resistance vessel function. Acute postprandial hyperlipidaemia has been shown to induce vascular dysfunction. In the present study, the impact of postprandial hyperglycaemia on resistance vessel reactivity was investigated in insulin treated type‐2 diabetic patients. The study was performed in 16 insulin treated type‐2 diabetics (eight male/eight female, age 47 ± 3 years, HbA1c 7·2 ± 0·2) and 16 controls. Reactive hyperaemia was measured in the forearm by venous occlusion plethysmography after 5 min of ischaemia in the fasting state and 90 min after a test meal. In diabetics, blood glucose increased from 8·7 ± 1·1 to 15·3 ± 1·0 mmol l^?1 (P<0·001) postprandially. This resulted in (i) a significant increase of resting blood flow (3·4 ± 0·3 to 4·8 ± 0·4 ml min^?1 100 ml^?1, P<0·01) and (ii) in a reduced peak reactive hyperaemia (52·3 ± 7·4 to 36·8 ± 4·3 ml min^?1 100 ml^?1, P<0·005). In controls, a similar effect of the meal on resting flow was observed but reactive hyperaemia was unaltered. In the absence of a test meal, basal flow as well as peak reactive hyperaemia remained unchanged in diabetic as well as in non‐diabetic subjects. Our data provide evidence that in the postprandial state resistance vessel reactivity becomes reduced in insulin treated type‐2 diabetic patients.