Anastasios Kollias

Studies of insulin resistance in patients with clinical and subclinical hyperthyroidism

OBJECTIVE Although clinical hyperthyroidism (HR) is associated with insulin resistance, the information on insulin action in subclinical hyperthyroidism (SHR) is limited. DESIGN AND METHODS To investigate this, we assessed the sensitivity of glucose metabolism to insulin in vivo (by an oral glucose tolerance test) and in vitro (by measuring insulin-stimulated rates of glucose transport in isolated monocytes) in 12 euthyroid subjects (EU), 16 patients with HR, and 10 patients with SHR. RESULTS HR and SHR patients displayed higher postprandial glucose levels (area under the curve, AUC(0)(-)(300) 32,190±1067 and 31,497±716,mg/dl min respectively) versus EU (27,119±1156 mg/dl min, P<0.05). HR but not SHR patients displayed higher postprandial insulin levels (AUC(0)(-)(300) 11,020±985 and 9565±904 mU/l min respectively) compared with EU subjects (AUC(0)(-)(300) 7588±743 mU/l min, P<0.05). Homeostasis model assessment index was increased in HR and SHR patients (2.81±0.3 and 2.43±0.38 respectively) compared with EU subjects (1.27±0.16, P<0.05), while Matsuda and Belfiore indices were decreased in HR (4.21±0.41 and 0.77±0.05 respectively, P<0.001) and SHR patients (4.47±0.33 and 0.85±0.05 respectively, P<0.05 versus EU (7.76±0.87 and 1 respectively). At 100 μU/ml insulin, i) GLUT3 levels on the monocyte plasma membrane were increased in HR (468.8±7 mean fluorescence intensity (MFI)) and SHR patients (522.2±25 MFI) compared with EU subjects (407±18 MFI, P<0.01 and P<0.05 respectively), ii) glucose transport rates in monocytes (increases from baseline) were decreased in HR patients (37.8±5%) versus EU subjects (61.26±10%, P<0.05). CONCLUSIONS Insulin-stimulated glucose transport in isolated monocytes of patients with HR was decreased compared with EU subjects. Insulin resistance was comparable in patients with both HR and SHR.

Prognosis of white-coat and masked hypertension: International Database of HOme blood pressure in relation to Cardiovascular Outcome.

Home blood pressure monitoring is useful in detecting white-coat and masked hypertension and is recommended for patients with suspected or treated hypertension. The prognostic significance of white-coat and masked hypertension detected by home measurement was investigated in 6458 participants from 5 populations enrolled in the International Database of HOme blood pressure in relation to Cardiovascular Outcomes. During a median follow-up of 8.3 years, 714 fatal plus nonfatal cardiovascular events occurred. Among untreated subjects (n=5007), cardiovascular risk was higher in those with white-coat hypertension (adjusted hazard ratio 1.42; 95% CI [1.06–1.91]; P=0.02), masked hypertension (1.55; 95% CI [1.12–2.14]; P<0.01) and sustained hypertension (2.13; 95% CI [1.66–2.73]; P<0.0001) compared with normotensive subjects. Among treated patients (n=1451), the cardiovascular risk did not differ between those with high office and low home blood pressure (white-coat) and treated controlled subjects (low office and home blood pressure; 1.16; 95% CI [0.79–1.72]; P=0.45). However, treated subjects with masked hypertension (low office and high home blood pressure; 1.76; 95% CI [1.23–2.53]; P=0.002) and uncontrolled hypertension (high office and home blood pressure; 1.40; 95% CI [1.02–1.94]; P=0.04) had higher cardiovascular risk than treated controlled patients. In conclusion, white-coat hypertension assessed by home measurements is a cardiovascular risk factor in untreated but not in treated subjects probably because the latter receive effective treatment on the basis of their elevated office blood pressure. In contrast, masked uncontrolled hypertension is associated with increased cardiovascular risk in both untreated and treated patients, who are probably undertreated because of their low office blood pressure.Home blood pressure monitoring is useful in detecting white-coat and masked hypertension and is recommended for patients with suspected or treated hypertension. The prognostic significance of white-coat and masked hypertension detected by home measurement was investigated in 6458 participants from 5 populations enrolled in the International Database of HOme blood pressure in relation to Cardiovascular Outcomes. During a median follow-up of 8.3 years, 714 fatal plus nonfatal cardiovascular events occurred. Among untreated subjects (n=5007), cardiovascular risk was higher in those with white-coat hypertension (adjusted hazard ratio 1.42; 95% CI [1.06–1.91]; P =0.02), masked hypertension (1.55; 95% CI [1.12–2.14]; P <0.01) and sustained hypertension (2.13; 95% CI [1.66–2.73]; P <0.0001) compared with normotensive subjects. Among treated patients (n=1451), the cardiovascular risk did not differ between those with high office and low home blood pressure (white-coat) and treated controlled subjects (low office and home blood pressure; 1.16; 95% CI [0.79–1.72]; P =0.45). However, treated subjects with masked hypertension (low office and high home blood pressure; 1.76; 95% CI [1.23–2.53]; P =0.002) and uncontrolled hypertension (high office and home blood pressure; 1.40; 95% CI [1.02–1.94]; P =0.04) had higher cardiovascular risk than treated controlled patients. In conclusion, white-coat hypertension assessed by home measurements is a cardiovascular risk factor in untreated but not in treated subjects probably because the latter receive effective treatment on the basis of their elevated office blood pressure. In contrast, masked uncontrolled hypertension is associated with increased cardiovascular risk in both untreated and treated patients, who are probably undertreated because of their low office blood pressure. # Novelty and Significance {#article-title-34}

Association of Central Versus Brachial Blood Pressure With Target-Organ Damage Systematic Review and Meta-Analysis

Accumulating evidence suggests that central blood pressure (BP) may reflect the hemodynamic stress on target organs more accurately than brachial BP. A systematic review assessing the relationship of central versus brachial BP with preclinical target-organ damage was performed. Meta-analysis of cross-sectional data showed that central compared with brachial systolic BP was more closely associated with (1) left ventricular mass index (12 studies, n=6431; weighted age [SD], 49.9 [13.1] years; 51% hypertensives): pooled correlation coefficients r=0.30; 95% confidence interval (CI), 0.23–0.37 versus r=0.26; 95% CI, 0.19–0.33, respectively; P<0.01 for difference; (2) carotid intima-media thickness (7 studies, n=6136; weighted age, 55.6 [13.2] years; 48% hypertensives): r=0.27; 95% CI, 0.19–0.34 versus r=0.23; 95% CI, 0.16–0.30, respectively; P<0.01 for difference; (3) pulse-wave velocity (14 studies, n=3699; weighted age, 53.9 [13.3] years; 53% hypertensives): r=0.42; 95% CI, 0.37–0.47 versus r=0.39; 95% CI, 0.33–0.45, respectively; P<0.01 for difference. Four studies assessing urine albumin excretion (n=3718; weighted age, 56.4 [5] years; 69% hypertensives) reported similar correlations (P=not significant) with central (r=0.22; 95% CI, 0.14–0.29) and brachial systolic BP (r=0.22; 95% CI, 0.12–0.32). Similar findings were observed for central compared with brachial pulse pressure in terms of relationship with target-organ damage. Metaregression analyses did not reveal any significant effect of age. In conclusion, central compared with brachial BP seems to be more strongly associated with most of the investigated indices of preclinical organ damage.

Automated blood pressure measurement in atrial fibrillation: a systematic review and meta-analysis.

Objective: The measurement of blood pressure in atrial fibrillation is considered as difficult and uncertain, and current guidelines recommend the use of the auscultatory method. The accuracy of automated blood pressure monitors in atrial fibrillation remains controversial. Method: A systematic review and meta-analysis was performed of studies comparing automated (oscillometric or automated Korotkov) versus manual auscultatory blood pressure measurements (mercury or aneroid sphygmomanometer) in patients with sustained atrial fibrillation. Results: Twelve validations were analyzed (566 patients; five home, three ambulatory and three office devices). Pooled correlation coefficients between automated and manual blood pressure measurements were stronger for SBP than DBP (r = 0.89 versus 0.76, P < 0.001). Automated measurements were higher than manual measurements [pooled average SBP difference 0.5 mmHg, 95% confidence interval (CI) −0.9, 1.9; DBP 2.5 mmHg, 95%CI −0.6, 5.7). The mean difference was within 5 mmHg in six and four (SBP and DBP, respectively) of six validations. The SD of mean difference was within 8 mmHg in two and three (SBP and DBP, respectively) of four validations. The proportion of absolute automated–manual differences within 5 mmHg was at least 65% in four and two (SBP and DBP, respectively) of eight validations. Three studies showed no impact of heart rate on the automated–manual blood pressure differences. Conclusion: There is limited evidence and significant heterogeneity in the studies that validated automated blood pressure monitors in atrial fibrillation. These monitors appear to be accurate in measuring SBP but not DBP. Given that atrial fibrillation is common in the elderly, in whom systolic hypertension is more common and important than diastolic hypertension, automated monitors appear to be appropriate for self-home but not for office measurement.

Ambulatory arterial stiffness index: A systematic review and meta-analysis

OBJECTIVE The dynamic relationship between 24 h diastolic and systolic ambulatory blood pressure (BP) expressed by the ambulatory arterial stiffness index (AASI) has been introduced as a novel measure of arterial function, which independently predicts cardiovascular mortality. This article reviews the published evidence on the features and the clinical relevance of AASI. METHODS A systematic review and meta-analysis of the evidence on AASI from 51 cross-sectional and longitudinal studies in adults was conducted. RESULTS Studies of the reproducibility of AASI have shown a mean difference between assessments at 0.014 (95% CI -0.001, 0.028; 3 studies, n = 451) and repeatability coefficients ranging from 0.24 to 0.40. AASI appears to be independently associated with age, systolic BP and pulse pressure, and inversely with the nocturnal systolic and diastolic BP decline. A moderate pooled association of AASI with 24 h pulse pressure (pooled correlation coefficient r 0.47, 95% CI 0.40, 0.54; 20 studies, n = 29,186) and pulse wave velocity (pooled r 0.30, 95% CI 0.19, 0.42; 9 studies, n = 4123) was demonstrated, as well as with other measures of arterial function and target-organ damage. The adjusted pooled hazard ratio for stroke corresponding to a study-specific one standard deviation increase in AASI was 1.26 (95% CI 1.08, 1.45; 3 studies, n = 14,320). CONCLUSIONS The available evidence suggests that AASI, obtained by ambulatory BP monitoring, predicts future cardiovascular events, particularly stroke, and is associated with indices of arterial function. The precise pathophysiological mechanisms remain obscure. Research is required to determine the usefulness of AASI as a therapeutic target in clinical practice.

Association of Central Versus Brachial Blood Pressure With Target-Organ Damage

Accumulating evidence suggests that central blood pressure (BP) may reflect the hemodynamic stress on target organs more accurately than brachial BP. A systematic review assessing the relationship of central versus brachial BP with preclinical target-organ damage was performed. Meta-analysis of cross-sectional data showed that central compared with brachial systolic BP was more closely associated with (1) left ventricular mass index (12 studies, n=6431; weighted age [SD], 49.9 [13.1] years; 51% hypertensives): pooled correlation coefficients r=0.30; 95% confidence interval (CI), 0.23–0.37 versus r=0.26; 95% CI, 0.19–0.33, respectively; P<0.01 for difference; (2) carotid intima-media thickness (7 studies, n=6136; weighted age, 55.6 [13.2] years; 48% hypertensives): r=0.27; 95% CI, 0.19–0.34 versus r=0.23; 95% CI, 0.16–0.30, respectively; P<0.01 for difference; (3) pulse-wave velocity (14 studies, n=3699; weighted age, 53.9 [13.3] years; 53% hypertensives): r=0.42; 95% CI, 0.37–0.47 versus r=0.39; 95% CI, 0.33–0.45, respectively; P<0.01 for difference. Four studies assessing urine albumin excretion (n=3718; weighted age, 56.4 [5] years; 69% hypertensives) reported similar correlations (P=not significant) with central (r=0.22; 95% CI, 0.14–0.29) and brachial systolic BP (r=0.22; 95% CI, 0.12–0.32). Similar findings were observed for central compared with brachial pulse pressure in terms of relationship with target-organ damage. Metaregression analyses did not reveal any significant effect of age. In conclusion, central compared with brachial BP seems to be more strongly associated with most of the investigated indices of preclinical organ damage.

Out-of-office blood pressure and target organ damage in children and adolescents: a systematic review and meta-analysis.

Objective: In children, out-of-office blood pressure (BP) assessment (especially ambulatory monitoring) is regarded as indispensable for accurate hypertension diagnosis. This article reviewed the evidence on the association between out-of-office BP measurements and preclinical organ damage indices in children. Methods: A systematic review and meta-analysis of 93 relevant articles (1974–2012) was performed. Results: Analysis of 10 studies (n = 480, pooled age 14.4 years, with hypertension 33%, renal disease 27%, type 1 diabetes 10%) revealed a significant association between systolic ambulatory BP and left ventricular mass index (LVMI), with pooled correlation coefficient r = 0.40 [95% confidence interval (CI) 0.30–0.50]. Eleven studies reported data on LVMI differences between normotensive (n = 428) and hypertensive children (n = 432), with higher values in the latter group by 6.53 g/m2.7 (95% CI 4.73–8.33). A moderate association was found between systolic ambulatory BP and carotid intima–media thickness (three studies, n = 231, age 13.3 years, pooled r = 0.32, 95% CI 0.21–0.44), as well as between diastolic ambulatory BP and urine albumin excretion (five studies, n = 355, age 13.1 years, type 1 diabetes 42%, reflux nephropathy 28%, pooled r = 0.32, 95% CI 0.05–0.58). Two studies reported on the association between home BP and LVMI, with one of them showing comparable coefficients as for ambulatory monitoring. Conclusion: The available evidence suggests a moderate but significant association between ambulatory BP and preclinical organ damage, mainly based on studies in nephropathy and/or diabetes. More data are needed in essential hypertension without nephropathy or diabetes, as well as with home measurements.

Visceral adiposity index is highly associated with adiponectin values and glycaemic disturbances

Visceral Adiposity Index (VAI) is a gender‐specific mathematical index estimated with the use of simple anthropometric (body mass index and waist circumference) and biochemical (triglycerides and high density lipoprotein cholesterol) parameters. Recent studies have shown that VAI reflects accurately the degree of visceral adiposity and insulin resistance. However, up to now, VAI has not been evaluated if it correlates with carbohydrate metabolism disorders, as well as with adipokine secretion from the fat mass.

Methodology and technology for peripheral and central blood pressure and blood pressure variability measurement: Current status and future directions - Position statement of the European Society of Hypertension Working Group on blood pressure monitoring and cardiovascular variability

Office blood pressure measurement has been the basis for hypertension evaluation for almost a century. However, the evaluation of blood pressure out of the office using ambulatory or self-home monitoring is now strongly recommended for the accurate diagnosis in many, if not all, cases with suspected hypertension. Moreover, there is evidence that the variability of blood pressure might offer prognostic information that is independent of the average blood pressure level. Recently, advancement in technology has provided noninvasive evaluation of central (aortic) blood pressure, which might have attributes that are additive to the conventional brachial blood pressure measurement. This position statement, developed by international experts, deals with key research and practical issues in regard to peripheral blood pressure measurement (office, home, and ambulatory), blood pressure variability, and central blood pressure measurement. The objective is to present current achievements, identify gaps in knowledge and issues concerning clinical application, and present relevant research questions and directions to investigators and manufacturers for future research and development (primary goal).

Genetic variation in the adiponectin receptor 2 (ADIPOR2) gene is associated with coronary artery disease and increased ADIPOR2 expression in peripheral monocytes

BackgroundAdiponectin is an adipose tissue secreted protein known for its insulin sensitising and anti-atherogenic actions. To this date two adiponectin receptors have been discovered, adiponectin receptor 1 (ADIPOR1) and adiponectin receptor 2 (ADIPOR2). The aim of this study was to investigate the association of ADIPOR2 gene variations with coronary artery disease (CAD).MethodsEight common single nucleotide polymorphisms (SNPs) spanning the entire ADIPOR2 locus were chosen to perform association studies with anthropometric and metabolic parameters in a Greek population. They were classified as either CAD (stenosis >50% in at least one main vessel) or non-CAD individuals in accordance with coronary angiography data.Genotyping was performed using a microsphere-based suspension array and the Allele Specific Primer Extension (ASPE) method. Expression of ADIPOR2 protein and mRNA in circulating CD14+ monocytes were determined using flow cytometry and real time Polymerase Chain Reaction assays respectively.ResultsThere was a significant difference in the distribution of genotypes of polymorphism rs767870 of ADIPOR2 between CAD and non-CAD individuals (p = 0.017). Furthermore, heterozygotes of the rs767870 polymorphism had significantly lower Flow Mediated Dilatation (FMD) values, higher values of Intima-Media Thickness (IMT) and increased ADIPOR2 protein levels in peripheral monocytes, compared to homozygotes of the minor allele after adjustment for age, sex, waist to hip ratio and HOMA.ConclusionsOur findings suggest that variants of ADIPOR2 could be a determinant for atherosclerosis independent of insulin resistance status, possibly by affecting ADIPOR2 protein levels.