A useful predictor of early atherosclerosis in obese children: serum high-sensitivity C-reactive protein

Childhood obesity seems to contribute to the development of vascular inflammation and the progression of arterial wall changes. High-sensitivity C-reactive protein (hs-CRP) has recently emerged as a useful biomarker for vascular inflammation associated with atherosclerosis. The objectives of this study were to evaluate the association of the serum hs-CRP level with ultrasonic findings of early atherosclerosis, carotid intima-media wall thickness (IMT) and brachial flow-mediated dilation (FMD), in obese children. Thirty eight obese children and 45 sex/age-matched healthy control children were recruited. Serum CRP levels were measured by the high-sensitive latex turbidimetric immunoassay, and we measured carotid IMT and brachial FMD using high-resolution B-mode ultrasonography. Obese children had significantly higher hs-CRP levels (1.40+/-0.74 mg/L vs. 0.55+/-0.49 mg/L, p<0.01), as well as increased IMT (0.52+/-0.09 mm vs. 0.41+/-0.07 mm, p<0.01) and impaired FMD (7.35+/-7.78% vs. 20.34+/-16.81%, p<0.01) compared to healthy controls. Serum hs-CRP correlated positively with IMT (r=0.413, p<0.05) and inversely with FMD (r=-0.350, p<0.05) in the obesity group. Measurement of the serum hs-CRP level is a simple, cheap, and highly reproducible assay and correlates with IMT and FMD in obese children. Thus, it would be a useful marker for evaluating and estimating the degree of atherosclerosis in children.     

Sleep apnea & automobile crashes.

BACKGROUND: As a group, patients with obstructive sleep apnea (OSA) are at increased risk of having automobile accidents. Previous studies using actual accident data have used only small numbers of subjects. OBJECTIVE: To determine the rate of automobile accidents in a large population of OSA patients using objective data from the Ministry of Transportation of Ontario (MTO). DESIGN: Retrospective study SETTING: Academic sleep disorders clinic and laboratory. PARTICIPANTS: All cases of OSA polygraphically confirmed between June 1990 and June 1994. INTERVENTIONS: Cases of OSA were a priori divided into groups based on apnea-hypopnea index (AHI): (OSA1 - AHI 10-25, OSA2 - AHI 26-40, OSA3 - AHI>40) and driving records were obtained from the MTO. Age and sex matched controls were selected at random from drivers in the MTO driver database who hold passenger vehicle licences. Analysis was restricted to drivers with the same licence class. MAIN OUTCOME MEASURES: Primary outcome measure was accidents in the five years preceding diagnosis. Secondary outcome was citations during the same period. RESULTS: There were 155 of 460 OSA patients with one or more accidents compared with 150 of 581 Controls for the same time period (x2=7.7,p<0.01).The rate of accidents/year, for the preceding five years, was 0.07+/-0.14 for Controls versus 0.09+/-0.14 for OSA (p <0.05). This difference could all be accounted for by increased accident rate in OSA patients with the highest AHI (OSA3) (MVA/yr: 0.11+/-0.15, 0.08+/-0.12, 0.06+/-0.14 for OSA groups 3,2,1 respectively) as there was no differences among Control, OSA1 and OSA2 accident rates. OSA patients had twice as many citations as Controls (1.74+/-2.13 vs 0.86+/-1.43 p<0.001) although the types of citation were the same. CONCLUSIONS: Increased automobile accidents in OSA may be restricted to cases with more severe apnea (AHI >40). Despite the large sample size (an order of magnitude greater than previous reports using accident data) further study is needed with even larger numbers, including more measures of disease severity and rigorously controlling for driving exposure.     

Intima-media thickness in treated and untreated patients with and without familial hypercholesterolemia: A systematic review and meta-analysis

Familial hypercholesterolemia (FH) is a common genetic disorder of lipoprotein metabolism leading to premature atherosclerosis. From early onset, status and progression of atherosclerosis of the large peripheral arterial walls can be quantified by ultrasound intima-media thickness (IMT) measurements. Here we describe differences in IMT in treated and untreated FH patients versus unaffected controls over a broad age range. We conducted a systematic literature search using MEDLINE, EMBASE and Trials.gov up to April 2020 for studies addressing IMT in FH patients and controls. Our search yielded 558 articles of which 42 (6,143 participants) were included. Meta-analysis showed a mean (95%CI) difference between FH patients vs controls of 0.11 (95%CI 0.06-0.15) mm in carotid IMT (p<0.001), and 0.47 (0.19-0.74) mm in femoral IMT (p <0.001). We found a smaller mean (95%CI) difference in carotid IMT in treated FH patients vs controls: 0.05 (0.03-0.08) mm (p <0.001), than in untreated FH patients vs controls 0.12 (0.03-0.21) mm (p=0.009). When plotted against age, the mean (95%CI) difference in carotid IMT between FH patients vs controls increases with 0.0018 (-0.0007-0.0042) mm/year. This increase was smaller in treated vs untreated FH patients, when compared to controls (0.0023 (0.0021 to 0.0025) mm/year vs 0.0104 (0.0100-0.0108) mm/year, respectively). Our findings suggest that more robust earlier treatment initiation and achieving treatment targets could be beneficial to reduce cardiovascular risk in patients with FH.     

Obstructive sleep apnea is associated with increased urinary albumin excretion

BACKGROUND: Obstructive sleep apnea (OSA) is associated with cardiovascular disease through incompletely understood mechanisms. Urinary albumin excretion is a surrogate for endothelial dysfunction and a potent cardiovascular disease risk predictor. We sought to determine whether urinary albumin excretion is increased in subjects with OSA. METHODS: Four hundred ninety-six adults, representing a spectrum of OSA severity, underwent overnight polysomnography and urine collection. OSA severity was assessed using the apnea-hypopnea index (AHI). The primary outcome measure was the adjusted albumin-to-creatinine ratio (aACR). Linear mixed models were used to assess the association between AHI category and aACR, adjusted for confounders and renal dysfunction. RESULTS: Subjects had a mean age of 44 +/- 17 (SD) years and approximately half were men (44%) and African American (56%). The percentages of subjects with mild (AHI 5-14), moderate (AHI 15-29), and severe (AHI > or = 30) OSA were 23%, 15%, and 15%, respectively. The median aACR for the entire sample was 4.3 mg/g (interquartile range: 2.9, 7.5). Adjusted linear mixed-model analyses showed a significant association between AHI category and aACR, with the AHI > or = 30 group having the highest aACR levels (7.87 +/- 1.02 mg/g vs 5.08 +/- 0.41 mg/g for those with AHI < 5; P < 0.006). Similar findings were observed after excluding subjects with renal dysfunction. CONCLUSION: OSA is significantly associated with increased urine albumin excretion, especially among those with more severe disease. These data provide further evidence supporting endothelial dysfunction as a mediating pathway between cardiovascular disease and OSA.     

Acute effects of paroxetine on genioglossus activity in obstructive sleep apnea

STUDY OBJECTIVE: To determine the acute effects of paroxetine on genioglossus activity during NREM sleep. DESIGN: A single dose of Paroxetine (40 mg) or placebo was administered four hours before bedtime on nights separated by one week in a double blind randomized crossover manner. The moving time average of genioglossus muscle activity (EMGgg) expressed as a percentage of maximum was measured using a mouthpiece electrode customized for each subject. The peak inspiratory and tonic values of EMGgg and the corresponding esophageal pressure deflections (DP) during the last three occluded breaths of obstructive apneas during NREM sleep were analyzed. SETTING: NA. PARTICIPANTS: 8 adult men with severe obstructive sleep apnea (OSA). INTERVENTIONS: NA. MEASUREMENTS AND RESULTS: Paroxetine increased the peak inspiratory EMGgg (29.8+/-2.4 (SE) versus 24.4+/-2.7 % max, p<0.05) and peak EMGgg/DP ratio (0.78+/-0.12 versus 0.65+/-0.11 % max/cm H2O, p<0.01) but not the tonic EMGgg (11.6+/-0.9 versus 9.8+/-0.7 % max) nor the DP (39.4+/-2.2 versus 38.2+/-2.8 cm H2O). Linear regression analysis of the peak inspiratory EMGgg versus DP relationship showed that paroxetine increased the slope (0.62+/-0.11 versus 0.49+/-0.09 % max/cm H2O, p<0.01). However, the apnea + hypopnea index (paroxetine: 75.2+/-5.5 versus placebo: 73.7+/-6.9 events/hour) did not differ. CONCLUSIONS: Paroxetine augmented peak inspiratory genioglossus activity during NREM sleep but this effect was not sufficient to decrease the frequency of obstructive apnea in this group with severe OSA.     

Evaluation of metabolic syndrome frequency and premature carotid atherosclerosis in young women with polycystic ovary syndrome

BACKGROUND: The aim of this study was to evaluate metabolic syndrome frequency, cardiovascular risk profile and premature carotid artery atherosclerosis in patients with polycystic ovary syndrome (PCOS) especially during early adulthood. METHODS: A case-control study was conducted on 43 young women (18-22 years of age) with PCOS and 43 age-matched volunteer controls. Anthropometrical measurements, hormone levels, lipid and glucose profile were obtained from all subjects. Two different criteria were used to assess metabolic syndrome (MS) frequency. Common carotid artery intima-media thickness (IMT) was measured and stepwise multiple linear regression analysis was used to identify the independent cardiovascular risk factors that predict IMT. RESULTS: MS was diagnosed in 11.6% (n = 5) of women with PCOS compared to no cases in the control group (P = 0.02). The mean IMT was significantly higher in PCOS subjects (0.746 +/- 0.106 mm) compared to controls (0.608 +/- 0.105 mm, P < 0.001). Among many cardiovascular risk factors evaluated, the diagnosis of PCOS, increased body mass index and decreased sex hormone-binding globulin were significant independent predictors of increased IMT. CONCLUSIONS: These findings indicate that adolescence may be a more appropriate time to intervene for PCOS patients, as many cardiovascular risks are already present during early adulthood. As far as IMT is concerned, mechanisms other than hyperandrogenaemia and obesity might be operating as causative factors.     

The impact of obstructive sleep apnea on homocysteine and carotid remodeling in metabolic syndrome

Obstructive sleep apnea (OSA) and metabolic syndrome (MetS) are associated with increased cardiovascular morbidity and mortality. Increased homocysteine is suggested as an independent risk factor for atherosclerosis and cardiovascular disease but remains disputed in OSA. We assessed polysomnography, carotid intima-media thickness (CIMT) and biology in 35 MetS patients, according to the presence (OSA+MetS; n=26) or the absence of OSA (MetS; n=9). In OSA+MetS patients, homocysteine levels were increased compared to MetS subjects (12.8 ± 3.8 vs. 9.5 ± 2.5 μmol/L; P=0.026). In the whole population, homocysteine correlated with apnea-hypopnea index (AHI) (r=0.522; P=0.001) and CIMT (r=0.376; P=0.026). Homocysteine was negatively correlated with plasma thiols (r=-0.406; P=0.017) and positively with urinary 15-F2t-isoprostanes (r=0.347; P=0.044). Multivariate regression analysis revealed that AHI (β=0.559; P<0.001) and urinary 15-F2t-isoprostane (β=0.310; P=0.018) were independently associated with homocysteine level. We conclude that homocysteine level was higher in MetS when associated with OSA and proportional to OSA severity. In this context, vascular remodeling appeared more severe and mediated by oxidative stress.     

Coronary artery calcification, common carotid artery intima-media thickness and aortic pulse wave velocity in patients on peritoneal dialysis

An increasing body of evidence suggests that atherosclerosis in patients with uremia differs from that found in general population in terms of advancement and localization of vascular lesions. It has also been suggested that different non-invasive techniques of vascular system evaluation are designed to show different types of lesions (i.e. vascular calcification, stiffness or 'classical' atherosclerosis). The aim of the study was to search for possible associations between results obtained with three different non-invasive methods of vascular system assessment in three different vascular sites in patients treated with peritoneal dialysis (PD). 61 patients (28 F, 33 M), mean age of 50.4+/-13.6 years, on maintenance PD for a median period of 10 months (range 1-96 months) were included. Coronary artery disease (CAD) was present in 21 subjects. In all subjects coronary artery calcification score (CaSc) using multi-row spiral computed tomography (MSCT), aortic pulse wave velocity (AoPWV) and ultrasound-based common carotid artery intima-media thickness (CCA-IMT) were performed as methods for assessing coronary calcium burden, arterial stiffness and atherosclerosis, respectively. Median value of CaSc equaled 11.5 Agatston units (range 0-5502.8 units). Median AoPWV was 10.4 m/s (range 7.56-18.1 m/s), and median CCA-IMT-0.6 mm (range 0.3-1.0 mm). In 16 patients (26.2%) at least one plaque in at least one common carotid artery was found on ultrasound. CaSc correlated with AoPWV (R=0.32, p<0.01) and with CCA-IMT (R=0.35, p<0.005), whereas no association was found between AoPWV and CCA-IMT. AoPWV, but not CaSc nor IMT correlated with blood pressure. The values of CCA-IMT and AoPWV increased together with consecutive Agatston categories (with p<0.001 for differences in AoPWV and p<0.05 for CCA-IMT). Patients with at least one plaque found in at least one CCA and patients with CAD were characterized with significantly higher values of CaSc, IMT and PWV, when compared to plaque-free and CAD- negative subjects, respectively. Association between CaSc and both IMT and PWV may suggest that the mechanism of three assessed vascular pathologies may be based, to some extent, on the process of pathologic calcium-phosphate deposition. Lack of correlation found between PWV and IMT may suggest that aortic stiffness and carotid atherosclerosis may partially differ in their pathologic background and/or are dissociated in time.     

Relationship of angiotensin-converting enzyme gene polymorphism to carotid wall thickness in middle-aged men

The insertion/deletion (I/D) polymorphism of the human angiotensin-converting enzyme (ACE) gene is a major determinant of circulating ACE levels. The D allele has been suggested to be a potent risk factor for coronary artery disease; however, the effect of the ACE gene on carotid atherosclerosis remains controversial. We therefore studied the relationship between the ACE gene I/D polymorphism and carotid artery intima-media thickness (IMT). A random sample of 300 men aged 50-59 years living in southern Finland were selected, and 233 agreed to participate (74%). Data were collected in 219 subjects. Quantitative B-mode ultrasonography was used to measure the maximum near and far wall IMT of right and left common, bifurcation, and internal carotid artery. The mean maximum IMT (overall mean) was calculated as the mean of 12 maximum IMTs at 12 standard sites. Patients with an IMT higher than 1.7 mm in at least one of 12 standard sites were assumed to have carotid atherosclerosis. The I/D polymorphism was determined by polymerase chain reaction. Overestimation of the frequency of the DD genotype was eliminated by insertion-specific primer and the inclusion of 5% dimethylsulfoxide. No significant differences were found in carotid wall thickness between the three genotypes; the overall mean IMT were 1.18 +/- 0.30, 1.22 +/- 0.24, and 1.08 +/- 0.40 mm in genotypes of II, ID, and DD, respectively. Similarly, the ACE genotypes and allele frequencies did not differ significantly between the subjects with and those without carotid atherosclerosis. There was no association in the subgroups among only nonsmoking subjects or subjects without chronic medication. The present data indicate that the I/D polymorphism of the ACE gene is not related to carotid IMT and is unlikely to play a major role in carotid atherosclerosis.     

Evaluation of pharyngeal shape and size using anatomical optical coherence tomography in individuals with and without obstructive sleep apnoea

This study compared shape, size and length of the pharyngeal airway in individuals with and without obstructive sleep apnoea (OSA) using a novel endoscopic imaging technique, anatomical optical coherence tomography (aOCT). The study population comprised a preliminary study group of 20 OSA patients and a subsequent controlled study group of 10 OSA patients and 10 body mass index (BMI)-, gender- and age-matched control subjects without OSA. All subjects were scanned using aOCT while awake, supine and breathing quietly. Measurements of airway cross-sectional area (CSA) and anteroposterior (A-P) and lateral diameters were obtained from the hypo-, oro- and velopharyngeal regions. A-P : lateral diameter ratios were calculated to provide an index of regional airway shape. In all subjects, pharyngeal CSA was lowest in the velopharynx. Patients with OSA had a smaller velopharyngeal CSA than controls (maximum CSA 91 +/- 40 versus 153 +/- 84 mm(2); P < 0.05) but comparable oro- (318 +/- 80 versus 279 +/- 129 mm(2); P = 0.48) and hypopharyngeal CSA (250 +/- 105 versus 303 +/- 112 mm(2); P = 0.36). In each pharyngeal region, the long axis of the airway was oriented in the lateral diameter. Airway shape was not different between the groups. Pharyngeal airway length was similar in both groups, although the OSA group had longer uvulae than the control group (16.8 +/- 6.2 versus 11.2 +/- 5.2 mm; P < 0.05). This study has shown that individuals with OSA have a smaller velopharyngeal CSA than BMI-, gender- and age-matched control volunteers, but comparable shape: a laterally oriented ellipse. These findings suggest that it is an abnormality in size rather than shape that is the more important anatomical predictor of OSA.     

Plasma levels of endothelin and early carotid atherosclerosis in diabetic patients.

An increased thickness of the carotid artery wall is thought to be a sign of early atherosclerosis. Since plasma endothelin concentrations were released from vascular endothelial cells, we have investigated the possible relationship between endothelin 1 (ET-1) and arterial wall thickness. Ninety-eight patients with Type 2 diabetes without evidence of macroangiopathy, hypertension, proteinuria or proliferative retinopathy, and 50 non-diabetic subjects were studied. After an overnight fast, blood was taken for ET-1, glucose, HbA1c, lipids, insulin and C-peptide. Arterial wall thickness was measured as the mean of the maximum intimal-medial thickness (IMT) in 16 carotid segments by B-mode ultrasound. ET-1 levels were significantly elevated in diabetic patients with IMT>1100 microm, 8.3 pmol/l (5.2-12.9) compared with control subjects, 7.6 pmol/l (5.0-11.0), p<0.01 and with diabetic subjects with IMT<500 microm, 7.43 pmol/l (4.8-11.1), p<0.01. The diabetic (IMT>1100 microm) study group had also significantly higher levels of insulin, 102.8 +/- 46.4 pmol/l vs control subjects, 77.5 +/- 32.4 pmol/l, p<0.01. In diabetic subjects, no correlation was found between ET-1 and IMT with glucose, HbA1c, lipids, age or duration of diabetes, respectively. We conclude that ET-1 levels are elevated in Type 2 diabetic patients with increased IMT. Thus providing further support for the role of endothelin in atherosclerosis.     

红斑狼疮患者外周血内皮祖细胞数量与颈动脉内膜-中膜厚度相关性研究

目的探讨系统性红斑狼疮（SLE）患者外周血内皮祖细胞（EPC）与颈动脉内膜-中膜厚度（IMT）的关系。方法连续选入40例SLE患者做为SLE组,超声检测颈动脉IMT按IMT增厚与否分为IMT正常组和IMT增厚组,20名门诊健康体检者为对照组。流式细胞分析计量外周血EPC（CD34和KDR双阳性细胞）;比较各组EPC数量及直线相关分析EPC数量和IMT相关性。结果SLE组外周血EPC数量较对照组显著减少,P〈0.01;同时在SLE组中IMT增厚组EPC数量低于IMT正常组,P〈0.01,且IMT与外周血EPC数量呈负相关（n=40,r=-0.494,P=0.006）。结论SLE患者存在早期动脉粥样硬化,外周血EPC数量降低与颈动脉IMT增加密切相关,外周血EPC数量降低可能是SLE引起早期动脉粥样硬化的重要原因之一。     

Hormone therapy is associated with preserved smooth muscle structure and dilation in the arterial vasculature of the leg in older women

Long-term hormone therapy (HT) is associated with reduced intima-medial thickness (IMT), an established risk factor for atherosclerotic disease, in the femoral artery of healthy older women relative to age-matched non-hormone users. However, the influence of continuous, long-term HT on the relation between age, IMT, and smooth muscle dilation has not been investigated in the popliteal artery, an artery prone to stiffening and calcification. In the present study, popliteal artery IMT and smooth muscle dilation (the increase in diameter to sublingual nitroglycerin, NTG) were assessed with Doppler ultrasound in young (Y: n=16; age 23+/-1 [mean+/-S.E.M.]), older non-HT (O non-HT: n=14; age 69+/-1), and older HT (O HT: n=8; age 67+/-1) healthy women. The approximately 0.5 mm increase in resting diameter observed in older non-HT women relative to young women was absent in older HT women, as was the age-related increase in IMT (Y: 0.52+/-0.02 mm; O non-HT: 0.63+/-0.02 mm; O HT: 0.56+/-0.02 mm; p<0.05 for age and hormone comparisons). NTG dilation (percent change above rest) was similarly attenuated in older non-HT women (Y: 8.6+/-1%; O non-HT: 3.0+/-0.7%; O HT: 7.4+/-1.7%; p<0.05 for age and hormone comparisons), and NTG dilation was inversely related to IMT (p<0.01). Collectively, these results suggest that long-term, continuous HT may alleviate the detrimental effects of aging on both structural changes and smooth muscle dilation of the popliteal artery in healthy women.     

The relationship between carotid and coronary atherosclerotic damage in dialysis patients

BACKGROUND: Data relating carotid ultrasound (CU) to atherosclerotic damage evaluated by coronary angiography in hemodialysis patients are scarce. METHODS: We carried out a cross-sectional study in 33 uremic subjects (age 55 +/- 12 years, 22 male, 7 diabetic), who have been on dialysis for 41 +/- 48 months (range 2-192). Twenty-two underwent a coronary angiography in order to complete clinical evaluation for inclusion on the kidney transplantation waiting list, and 11 because of coronary artery disease (CAD); Gensini's score was calculated. Intima-media thickness (IMT) and presence of plaques were related to the degree of coronary stenosis and to cardiovascular risk factors. Patients were divided into two groups depending on mean IMT (group 1 IM 0.9 mm, n=15). RESULTS: Group 2 was older (60 +/- 8 vs 50 +/- 12 year, p=0.01), had higher frequency of CAD (53 vs 16%, p=0.02) and had higher prevalence of coronary artery stenosis >or= 75% in the right (60 vs 22%, p=0.02), left anterior descending (46 vs 16%, p=0.06) and left circumflex coronary arteriers (60 vs 11%, p=0.05) than group 1. IMT was not related to the degree of CAD evaluated by Gensini's score. IMT sensibility and specificity in detecting the presence of hemodynamically significant coronary stenosis were 64% and 68%, respectively. Coronary narrowing was correlated with the degree of stenosis of common, internal and external carotid arteries (Spearman's rank correlation coefficient). During two years of follow-up, six major cardiac events were recorded and they were related to Gensini's score. CONCLUSIONS: In uremic patients, ultrasonographic evaluation of carotid arteries is a simple, noninvasive examination that could be a helpful tool in detecting coronary atherosclerotic damage, but IMT does not appear to add more information regarding risk stratification of CAD.     

Portable monitoring and autotitration versus polysomnography for the diagnosis and treatment of sleep apnea

STUDY OBJECTIVES: To compare a clinical pathway using portable monitoring (PM) for diagnosis and unattended autotitrating positive airway pressure (APAP) for selecting an effective continuous positive airway pressure (CPAP) with another pathway using polysomnography (PSG) for diagnosis and treatment of obstructive sleep apnea (OSA). DESIGN: Randomized parallel group SETTING: Veterans Administration Medical Center PATIENTS: 106 patients with daytime sleepiness and a high likelihood of having OSA MEASUREMENTS AND RESULTS: The AHI in the PM-APAP group was 29.2 +/- 2.3/h and in the PSG group was 36.8 +/- 4.8/h (P= NS). Patients with an AHI > or = 5 were offered CPAP treatment. Those accepting treatment (PM-APAP 45, PSG 43) were begun on CPAP using identical devices at similar mean pressures (11.2 +/- 0.4 versus 10.9 +/- 0.5 cm H2O). At a clinic visit 6 weeks after starting CPAP, 40 patients in the PM-APAP group (78.4% of those with OSA and 88.8% started on CPAP) and 39 in the PSG arm (81.2% of those with OSA and 90.6% of those started on CPAP) were using CPAP treatment (P = NS). The mean nightly adherence (PM-APAP: 5.20 +/- 0.28 versus PSG: 5.25 +/- 0.38 h/night), decrease in Epworth Sleepiness Scale score (-6.50 +/- 0.71 versus -6.97 +/- 0.73), improvement in the global Functional Outcome of Sleep Questionnaire score (3.10 +/- 0.05 versus 3.31 +/- 0.52), and CPAP satisfaction did not differ between the groups. CONCLUSIONS: A clinical pathway utilizing PM and APAP titration resulted in CPAP adherence and clinical outcomes similar to one using PSG.     

Endothelial dysfunction and microvascular complications in type 1 diabetes mellitus

We examined whether alterations in vascular endothelial function and early structural changes in atherosclerosis are associated with microvascular complications in patients with type 1 diabetes mellitus (DM). Flow-mediated dilation (FMD) of the brachial artery and carotid intima-media thickness (IMT) measurement were performed in 70 young adults (aged 19 to 35 yr), 48 with type 1 DM, and 22 normal controls. Patients with diabetes had a lower peak FMD response (7.8+/-3.9 vs. 11.1+/-1.9%, p<0.001) and increased IMT (0.51+/-0.10 vs. 0.42+/-0.07 mm, p<0.001) compared with controls. Twenty (41.7%) of the patients had microvascular complications including neuropathy, nephropathy, or retinopathy. In these complicated diabetic patients, we found a lower FMD response (6.1+/-2.5 vs. 9.9+/-3.5%, p=0.001) compared with diabetics without microvascular complications. The presence of microvascular complications was also associated with older age and longer duration of the disease. However, no differences were observed in IMT, body size, blood pressure, HbA1c, C-reactive protein, low-density lipoprotein or high-density lipoprotein cholesterol levels between complicated and non-complicated patients. Endothelial dysfunction and early structural atherosclerotic changes are common manifestations in type 1 DM, and endothelial dysfunction is thought to be an early event in the atherosclerotic process and important in the pathogenesis of microvascular complications.     

Influence of nasal resistance on oral appliance treatment outcome in obstructive sleep apnea

It has been recognized that nasal airway resistance (NAR) is elevated in patients with OSA. However, little is known regarding the influence of nasal resistance on mandibular advancement splint (MAS) treatment outcome in OSA patient. We hypothesized that nasal resistance differs between MAS responders and nonresponders and therefore may influence treatment outcome. Thirty-eight patients with known OSA underwent polysomnography while wearing a custom-made MAS. Treatment outcome was defined as follows: Responders (R) > or =50% reduction in AHI, and Nonresponders (NR) as <50% reduction in AHI. NAR was measured using posterior rhinomanometry in both sitting and supine positions, with and without MAS. The mean AHI in 26 responders was significantly reduced from 29.0 +/- 2.9/h to 6.7 +/- 1.2/h; P < 0.01). In 12 nonresponders there was no significant change in AHI (23.9 +/- 3.0/h vs 22.0 +/- 4.3/h; P=ns). Baseline NAR was significantly lower in responders in the sitting position compared to nonresponders (6.5 +/- 0.5 vs 9.4 +/- 1.0 cm H2O; P < 0.01). There was no significant change in NAR (from baseline) with MAS in either response group while in the sitting position, but in the supine position NAR increased significantly with MAS in the nonresponder group (11.8 +/- 1.5 vs. 13.8 +/- 1.6 cm H2O/L/s; P < 0.01). Logistic regression analysis revealed that NAR and BMI were the most important predictive factors for MAS treatment outcome. These data suggest that higher levels of NAR may negatively impact on treatment outcome with MAS.     

Progression of carotid atherosclerosis and the role of endothelin in diabetic patients.

An increased thickness of the carotid artery wall is thought to be a sign of early atherosclerosis. Since vascular endothelium is the site of formation of several substances, we have investigated the rate of progression of carotid atherosclerosis and the contribution of endothelin (ET-1), lipid peroxides [measured as thiobarbituric acid reacting species (TBARS)] and 6-keto-Prostaglandin-F1A (6-keto-PG-F1A) at baseline and after 30-months. Fifty patients with Type 2 diabetes without evidence of macroangiopathy, hypertension, proteinuria or proliferative retinopathy, and 27 healthy, non-diabetic persons were studied. Arterial wall thickness was measured as the mean of the maximum intimal-medial thickness (IMT) in 16 carotid segments by b-mode ultrasound. The IMT values was significantly increased in diabetic subjects (at baseline: 1110 +/- 310 microm, after 30 months: 1260 +/- 280 microm, p < 0.01), but not in control subjects (1100 +/- 280 microm, 1200 +/- 290 microm, respectively). At baseline time both groups had similar levels of ET-1, TBARS and 6-keto-PG-F1A. In 30-months follow-up, the ET-1 level 8.0 pmol/l (5.8-10.7) was significantly elevated in diabetic subjects, compared with the level at baseline time 7.43 pmol/l (4.8-11.1) p < 0.01. No significant differences were found in the other examined parameters in the studied groups. Although insulin levels remained unchanged in the two studied groups, in 30 months follow-up, the insulin level in the diabetic subjects, 92.4 +/- 35.1 pmol/l was significantly elevated compared with those of control subjects 76.0 +/- 31.0 pmol/l, p < 0.05. In conclusion, endothelis is the main associate of the change of IMT value over 30 months in diabetic patients, in whom the extent of atherosclerosis was significantly greater than in control subjects.     

Consequences of Comorbid Sleep Apnea in the Metabolic Syndrome—Implications for Cardiovascular Risk

Study Objectives:

Metabolic syndrome (MetSyn) increases overall cardiovascular risk. MetSyn is also strongly associated with obstructive sleep apnea (OSA), and these 2 conditions share similar comorbidities. Whether OSA increases cardiovascular risk in patients with the MetSyn has not been investigated. We examined how the presence of OSA in patients with MetSyn affected hemodynamic and autonomic variables associated with poor cardiovascular outcome.

Design:

Prospective clinical study.

Participants:

We studied 36 patients with MetSyn (ATP-III) divided into 2 groups matched for age and sex: (1) MetSyn+OSA (n = 18) and (2) MetSyn-OSA (n = 18).

Measurements:

OSA was defined by an apnea-hypopnea index (AHI) > 15 events/hour by polysomnography. We recorded muscle sympathetic nerve activity (MSNA - microneurography), heart rate (HR), and blood pressure (BP - Finapres). Baroreflex sensitivity (BRS) was analyzed by spontaneous BP and HR fluctuations.

Results:

MSNA (34 ± 2 vs 28 ± 1 bursts/min, P = 0.02) and mean BP (111 ± 3 vs. 99 ± 2 mm Hg, P = 0.003) were higher in patients with MetSyn+OSA versus patients with MetSyn-OSA. Patients with MetSyn+OSA had lower spontaneous BRS for increases (7.6 ± 0.6 vs 12.2 ± 1.2 msec/mm Hg, P = 0.003) and decreases (7.2 ± 0.6 vs 11.9 ± 1.6 msec/mm Hg, P = 0.01) in BP. MSNA was correlated with AHI (r = 0.48; P = 0.009) and minimum nocturnal oxygen saturation (r = −0.38, P = 0.04).

Conclusion:

Patients with MetSyn and comorbid OSA have higher BP, higher sympathetic drive, and diminished BRS, compared with patients with MetSyn without OSA. These adverse cardiovascular and autonomic consequences of OSA may be associated with poorer outcomes in these patients. Moreover, increased BP and sympathetic drive in patients with MetSyn+OSA may be linked, in part, to impairment of baroreflex gain.

Citation:

Trombetta IC; Somers VK; Maki-Nunes C; Drager LF; Toschi-Dias E; Alves MJNN; Fraga RF; Rondon MUPB; Bechara MG; Lorenzi-Filho G; Negrão CE. Consequences of comorbid sleep apnea in the metabolic syndrome—implications for cardiovascular risk. SLEEP 2010;33(9):1193-1199.     

Effect of whole body resistance training on arterial compliance in young men

The effect of resistance training on arterial stiffening is controversial. We tested the hypothesis that resistance training would not alter central arterial compliance. Young healthy men (age, 23 +/- 3.9 (mean +/- s.e.m.) years; n = 28,) were whole-body resistance trained five times a week for 12 weeks, using a rotating 3-day split-body routine. Resting brachial blood pressure (BP), carotid pulse pressure, carotid cross-sectional compliance (CSC), carotid initima-media thickness (IMT) and left ventricular dimensions were evaluated before beginning exercise (PRE), after 6 weeks of exercise (MID) and at the end of 12 weeks of exercise (POST). CSC was measured using the pressure-sonography method. Results indicate reductions in brachial (61.1 +/- 1.4 versus 57.6 +/- 1.2 mmHg; P < 0.01) and carotid pulse pressure (52.2 +/- 1.9 versus 46.8 +/- 2.0 mmHg; P < 0.01) PRE to POST. In contrast, carotid CSC, beta-stiffness index, IMT and cardiac dimensions were unchanged. In young men, central arterial compliance is unaltered with 12 weeks of resistance training and the mechanisms responsible for cardiac hypertrophy and reduced arterial compliance are either not inherent to all resistance-training programmes or may require a prolonged stimulus.