Akihiko Abiko

Effects of telmisartan on adiponectin levels and body weight in hypertensive patients with glucose intolerance

Few studies have analyzed intraclass differences in angiotensin II receptor blockers (ARBs) with respect to antidiabetic or metabolic effects. We designed a prospective randomized study to compare a peroxisome proliferator-activated receptor-gamma (PPARgamma)-activating ARB with a nonactivating ARB to delineate the effects on metabolic factors associated with cardiovascular disease. Subjects initially comprised 153 hypertensive patients (72 men, 81 women; mean age, 67.9 +/- 7.8 years) with diagnosed glucose intolerance on the glucose loading test. Patients were randomly assigned to receive 6-month administration of telmisartan 47.0 mg/d (TEL) or candesartan 8.4 mg/d (CAN), or to have no change in drug regimen (control group, CTL). Fasting plasma glucose level was significantly reduced in TEL (n = 46) compared with CTL (n = 47) (percentage of change from baseline, -1.7% vs +2.2%; P = .045). Percentage of increase in adiponectin was significantly larger in TEL than in CTL (+10.5% vs +2.2%, P = .025), but not significantly larger in CAN (n = 44) than in CTL (+4.9% vs +2.2%; P = .13). Percentage of decrease in body weight from baseline was significantly enhanced in TEL compared with CTL (-2.2% vs -0.8%, P = .023) and CAN (-2.2% vs -0.3%, P = .007). Telmisartan decreased body weight while increasing serum adiponectin levels in hypertensive patients with glucose intolerance. Candesartan did not achieve similar improvements in these patients. Among ARBs, telmisartan may have a larger impact on obesity-related diseases that can lead to cardiovascular disorders.

Low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio as a useful marker for early-stage carotid atherosclerosis

A higher ratio of low-density lipoprotein cholesterol (LDL-C) to high-density lipoprotein cholesterol (HDL-C) is associated with a greater risk of cardiovascular events in patients with coronary heart disease. However, the role of this lipid index during early-stage atherosclerosis has not yet been established. This study investigated relationships between LDL-C/HDL-C ratio and carotid plaque score as assessed by ultrasonography in 825 subjects from the general population (527 men, 298 women; mean age, 60.5 years). To identify factors strongly associated with plaque score, stepwise multiple regression analysis was performed using various clinical variables including conventional lipid indices. In both sexes, increased LDL-C/HDL-C ratio was associated with increased plaque score (men: beta = 0.132, P = .001; women: beta = 0.150, P = .012). This association was maintained in men with normal LDL-C level (<140 mg/dL). The highest quartile of LDL-C/HDL-C ratio (>2.9 in men, >2.6 in women) showed significantly increased plaque score even when adjusted by factors included in the final model of stepwise analysis (P = .007 in men, P = .033 in women). No association was seen between LDL-C and plaque score in the multivariate-adjusted model. These findings indicate that increased LDL-C/HDL-C ratio may also be associated with initiation of atherosclerosis. Assessment of this lipid ratio may thus facilitate early management of atherosclerotic risks better rather than assessment of LDL-C alone.

Potential effects of angiotensin II receptor blockers on glucose tolerance and adiponectin levels in hypertensive patients.

Some classes of antihypertensive agents, notably angiotensin II receptor blockers (ARBs), are known to reduce the incidence of new-onset DM. Compared with other ARBs, telmisartan, which has a partial agonist effect on the peroxisome proliferator-activated receptor-γ (PPAR-γ) [1, 2], is expected to have particularly useful effects. However, few studies have analyzed intra-class ARB differences with respect to their antidiabetic effects or metabolic effects. Adiponectin is one of the adipocyte-derived hormones that has profound anti-inflammatory and antiatherogenic properties. Adiponectin has also been postulated to play an important role in the modulation of glucose and lipid metabolism. A reduced adiponectin level is thought to play a role in the pathogenesis of cardiovascular diseases. The effect that ARBs and other antihypertensive agents have on serum adiponectin levels and glucose intolerance was investigated by doing a cross-sectional analysis. The study population was recruited from consecutive hypertensive outpatients treated with antihypertensive drugs at our university hospital and Saiki hospital (n=281; 135 males; average age, 66.9 years; range, 40–80 years). Patients were included in the study if their antihypertensive or lipid lowering drugs had not changed in the past year. Patients who had been previously diagnosed as having DM or impaired glucose tolerance (IGT), and those who had clinically evident atherosclerotic diseases, such as coronary artery, peripheral artery, or cerebrovascular disease, were excluded. In all patients, fasting blood samples were obtained for routine evaluation of hematology and biochemical parameters, including the insulin concentration. Serum adiponectin levels were measured using ELISA. A 75 g oral glucose tolerance test (75 gOGTT) was also done. Using the WHO criteria, patients were classified into three groups: the normal glucose tolerance (NGT) group; the IGT group; and the DM group. Data are expressed as means ± SD. Sixty-nine patients (24.6%) with DM and 109 patients (38.8%) with IGT were newly diagnosed based on the 75 g OGTT results. The antihypertensive agents that were used by the subjects, the incidence of DM, and the association between each agent that was used and the serum adiponectin level are shown in Table 1. The percentage of patients who had DM (17.2%) was significantly lower among patients taking ARBs than among patients not taking ARBs (29.2%, p=0.023). There were no significant differences in the prevalence of DM between patients taking and not taking calcium antagonists, ACE inhibitors, β-blockers, or α-blockers. On multiple linear regression analysis, only the use of telmisartan was found to have a significant positive correlation with the serum adiponectin level when adjusted by age, gender, waist circumference, and statin use (coefficient 3.41, 95% confidence interval 1.40–5.41, p= 0.001); other ARBs and other classes of antihypertensive agents were not found to have a significant positive correlation with the serum adiponectin level (Table). There were no significant differences in the baseline characteristics or in the use of concomitant medications Cardiovasc Drugs Ther (2007) 21:317–318 DOI 10.1007/s10557-007-6039-x

Chronic kidney disease is associated with increased carotid artery stiffness without morphological changes in participants of health check-up programs

BACKGROUND AND METHODS Patients with chronic kidney disease (CKD) show a much higher risk of cardiovascular disease. However, the mechanisms underlying this association and the impact of CKD on behaviors of the vascular walls have not been fully clarified. Using ultrasonography, this study investigated associations of CKD (estimated glomerular filtration rate <60 ml/min/1.73 m(2) and/or presence of proteinuria) with both elasticity (stiffness β index) of the carotid artery and intimal atherosclerotic changes in participants of health check-up programs (n=3406, 63% men; mean age, 58.8 years). RESULTS Stiffness β was significantly higher in CKD subjects (7.49 ± 0.14) than in non-CKD subjects (6.87 ± 0.05, P<0.001). This significant difference was maintained in a multiple adjusted model including conventional risk factors such as hypertension, diabetes mellitus, dyslipidemia, smoking and obesity (7.20 ± 0.14 vs. 6.91 ± 0.05, P=0.043). No significant differences in intima-media complex thickness or plaque score were seen between CKD and non-CKD subjects. CONCLUSION In participants of health check-up programs, CKD was associated with increased carotid arterial stiffness without intimal disease, independently of conventional risk factors. These findings indicate that CKD may predispose the carotid arteries to earlier development of arteriosclerosis, characterized by increased arterial stiffness.

Intentional preservation of collateral circulation to the artery of Adamkiewicz using axillo-axillary bypass, concomitant with thoracic endovascular aneurysm repair

Figure 1: The left anterior lateral view of a volume-rendering image with semitransparent skeletal system shows that the left seventh intercostal artery (ICA 7), which is the origin of the artery of Adamkiewicz (arrowed), is occluded proximal to the aorta. This image also shows collateral circulation from the left internal thoracic artery (ITA) and muscular branch of the left ninth intercostal artery (ICA 9) to ICA 7. Figure 2: The left anterior lateral view of a volume-rendering image after the endovascular aneurysm repair shows full continuity from the ITA to the artery of Adamkiewicz (arrowed) via axillo-axillary bypass. Because of the coverage of ICA 9 by the stent graft and the left subclavian artery, axillo-axillary bypass was intentionally performed to preserve collateral circulation. In this case, we performed an axillo-axillary bypass instead of a direct left axillary-left carotid artery bypass or direct anastomosis, owing to concerns over the risk of cerebrovascular events.

Influence of daily alcohol consumption on serum adiponectin levels in men.

BACKGROUND The risk of cardiovascular diseases is lower among moderate alcohol drinkers than among both nondrinkers and heavy drinkers. However, factors that can account for the U-shaped or J-shaped relationship between daily alcohol consumption and incident cardiovascular diseases remain obscure. PURPOSE The present cross-sectional study investigated the relationship between alcohol consumption and serum adiponectin levels. METHOD Total adiponectin was measured in 527 males participating in health check-up programs (age range 40-86 years, mean 60.5 years). Based on questionnaire responses, alcohol intake was categorized into three groups: none or occasional (A1); <50 g/day and ≥3 days/week (A2); and ≥50 g/day and ≥3 days/week (A3). RESULTS No significant differences in adiponectin levels were observed among the three alcohol consumption groups of subjects without the metabolic syndrome (MetS). In subjects with the MetS, the adiponectin level was significantly higher in the A2 (moderate drinker) group than in both the A1 and A3 groups. MetS subjects in group A2 had higher HDL-C levels than those in A1, but levels in group A3 were not significantly different from those in group A2. CONCLUSION An increased adiponectin level in moderate alcohol drinkers who have MetS may contribute to the U-shaped relationship between alcohol consumption and risk of cardiovascular events, in addition to the involvement of HDL-C.

Diabetic state as a crucial factor for impaired arterial elastic properties in patients with peripheral arterial disease

BACKGROUND Increased arterial stiffness is associated with greater risk of cardiovascular events and mortality. However, in patients with peripheral arterial disease (PAD) who have severe atherosclerotic disorder or risk clustering, the major determinants of increased stiffness have been not clarified. METHODS This study investigated the associations between elastic properties of the carotid artery as measured by ultrasonography and atherosclerotic risk factors, with particular focus on diabetes mellitus (DM), in PAD patients (n=481; mean age, 69.6 years). DM was defined as hemoglobin A1c >/=6.5%, administration of anti-diabetic agents, or DM pattern on 75-g oral glucose tolerance test. Stiffness beta index was calculated from luminal diameter changes measured by the M-mode method using a linear array imaging probe. RESULTS Stiffness parameter beta was significantly increased in diabetic patients compared with non-diabetic patients (9.56+/-0.35 vs. 8.31+/-0.32; p=0.009) in an age- and gender-adjusted model. This significant difference was maintained in a multivariate-adjusted model including age, gender, hypertension, hyperlipidemia, obesity and smoking history (9.43+/-0.36 vs. 8.39+/-0.33; p=0.037). No significant differences in mean intima-media complex thickness or plaque score of the carotid artery were seen between diabetic and non-diabetic patients. CONCLUSION Diabetic condition impairs the elastic properties of arteries, independent of other known atherosclerotic risk factors or excessive intimal diseases in PAD patients. This may support the notion that diabetic condition can worsen prognosis for PAD patients.

Increased Carotid Artery Stiffness Without Atherosclerotic Change in Patients With Aortic Dissection

The arterial properties and pathogenesis of aortic dissection remain obscure. To examine the arterial properties of patients with aortic dissection, the authors studied the ultrasonographic characteristics of the carotid artery in patients with an aortic dissection (AD, n=86), and compared these findings with data of patients suffering from arteriosclerosis obliterans (ASO, n=151), coronary artery disease (CAD, n=163), and with healthy controls (HC, n=77). Atherosclerotic intimal changes, such as intima-media thickness (IMT) and plaque formation, were milder in AD than in ASO or CAD (IMT: 0.83 ±0.16 vs 0.93 ±0.20/0.86 ±0.17 mm, p<0.05; plaque number: 0.6 ±1.1 vs 2.7 ±2.4/2.5 ±2.1, p<0.05). Luminal diameter in AD, ASO, and CAD was significantly higher than in HC. The luminal distensibility in AD was decreased compared with HC but was the same as in ASO and CAD. Intra-AD group analysis showed that in patients with an intramural hematoma (IMH) or a dissection with a thrombosed false lumen (TLF) the IMT was higher than in patients with a classic dissection. In addition, plaque formation was more severe in AD patients with a coexisting abdominal aortic aneurysm (AAA). Reduced distensibility without severe intimal disease was found in AD. These findings suggest that patients with AD may have several arterial alterations, including structural abnormalities. Patients with IMH, TFL, or coexisting AAA may differ from patients who have a classic type of dissection or who do not have AAA, in terms of arterial characteristics including intimal disease and wall elastic property, and the initiating cause of the dissection. Introduction Owing to the progress that has been made in various imaging modalities, the improvement in the accuracy of diagnosing an aortic dissection has resulted in an increase in the detection rate of the various subtypes of classic dissection, such as those associated with an intramural hematoma (IMH), hemorrhage, or a penetrating atherosclerotic ulcer.1,2 However, the etiology and pathogenesis of these catastrophic aortic disorders remain obscure. From the clinical perspective, it has Angiology 57:478–486, 2006 From the Department of Medicine II, Iwate Medical University, Morioka, Japan Correspondence: DOI: 10.1177/0003319706290625 Copyright

Efficacy of Low-Dose Hydrochlorothiazide in Combination with Telmisartan on Early Morning Blood Pressure in Uncontrolled Hypertensive Patients

Hypertensive patients whose BP was uncontrolled despite the use of antihypertensive agents, including an ARB (candesartan 8 mg/day or valsartan 80 mg/day), were enrolled. The patients were randomly assigned to combination therapy with telmisartan 40 mg/day (changed from current ARB) and hydrochlorothiazide (HCTZ) 12.5 mg/day (T + H, n = 32) or to no change in their current drug regimen (CTL, n = 32). The observation period was 12 weeks. The office and home BPs were significantly reduced in the T + H compared to those in the CTL. A sufficient and long-acting BP lowering effect, as reflected in decreased early morning BP, was obtained with the combination of low-dose HCTZ and telmisartan without apparent metabolic deterioration.

Three-dimensional demonstration of the collateral circulation to the artery of Adamkiewicz via inferior epigastric artery with computed tomography angiography

Conflict of interest: none declared. Figure 1: The anterior view of volume-rendering image with semitransparent skeletal system, aorta and kidney shows that the left ICA 9, which is the origin of the artery of Adamkiewicz (arrow), is occluded proximally at the aorta. This image also shows collateral circulation to the artery of Adamkiewicz via the left inferior epigastric artery (IEA), the left 10th ICA and the muscular branch (arrowhead) between the left ICA 9 and the left ICA 10. Intentional preservation of the collateral circulation is planned by a median laparotomy with abdominal aortic graft replacement with careful wound retraction and cannulation from the left femoral artery for cardiopulmonary circulation. T9: 9th thoracic vertebra; ICA 10: 10th intercostal artery. Figure 2: A curved planar reformatted image shows full continuity from the left inferior epigastric artery (IEA) to the artery of Adamkiewicz (arrow) via the left 10th intercostal artery (ICA10).