Increased human urotensin II levels are correlated with carotid atherosclerosis in essential hypertension

BACKGROUND: Circulating blood levels of human urotensin II (U-II), the most potent vasoconstrictor peptide identified to date, are increased in patients with essential hypertension. Our previous studies showed that U-II accelerates human macrophage foam cell formation and vascular smooth muscle cell proliferation, suggesting development of atherosclerotic plaque. In this study, we demonstrated a correlation between plasma U-II level and progression of atherosclerosis in hypertensive patients. METHODS: The intima-media thickness (IMT) and plaque score in the carotid artery, blood pressure (BP), plasma levels of U-II, and atherosclerotic parameters were determined in 50 hypertensive patients and 31 normotensive controls. RESULTS: Plasma U-II level, maximum IMT, plaque score, systolic BP, and homeostasis model assessment for insulin resistance (HOMA-IR) were significantly greater in hypertensive patients than normotensive controls. Age, gender, body mass index, and serum levels of high-sensitive C-reactive protein (CRP), HDL and LDL cholesterols, small dense LDL, triglycerides, lipoprotein(a), insulin, and fasting plasma glucose level were not significantly different between the two groups. In all subjects, plasma U-II level showed significant positive correlations with systolic BP, maximum IMT, plaque score, and HOMA-IR. Multiple logistic regression analysis indicated that the contribution of plasma U-II levels to carotid plaque formation (plaque score >/=1.1) was significantly still greater with a 60% increase than those of established risk factors, such as age, systolic BP, high-sensitive CRP, small dense LDL, and HOMA-IR. CONCLUSIONS: Our results suggest that increased levels of U-II may play a crucial role in the development of carotid atherosclerosis in hypertensive patients.     

高血压合并颈动脉粥样硬化患者血清C-反应蛋白的水平变化

目的探索高血压合并颅外颈动脉粥样硬化患者血清C-反应蛋白的水平变化。方法对92例高血压患者采用血管外高分辨超声进行检测,以内膜-中层厚度≥1.0 mm或发现动脉斑块为阳性结果并用酶联免疫法检测血清C-反应蛋白水平。结果在92例高血压患者中,共检出颈动脉粥样硬化患者48例,检出率为52.2%,在男性和女性中,颈动脉粥样硬化检出率差异无统计学意义,合并颈动脉粥样硬化的高血压患者血清C-反应蛋白水平为[(3.2±2.4)mg/ml],高于无颈动脉粥样硬化并发症的高血压患者[(2.1±1.5)mg/ml](P0.05)。结论在高血压病患者中,C-反应蛋白与颈动脉粥样硬化密切相关。     

原发性高血压患者颈动脉粥样硬化与脂代谢的关系探讨

目的 探讨原发性高血压患者脂代谢与颈动脉粥样硬化的关系.方法 检测122例原发性高血压患者(观察组)与34例血压正常者(对照组)的血总胆固醇、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、载脂蛋白A、载脂蛋白B、脂蛋白a水平,同时进行颈动脉超声检查.结果 与对照组比较,观察组颈动脉内-中膜明显增厚、斑块形成明显增多;甘油三酯、低密度脂蛋白胆固醇、载脂蛋白B、脂蛋白a明显增高.结论 原发性高血压患者的脂类代谢异常与颈动脉内-中膜增厚及斑块形成有关.及时检测原发性高血压患者的血脂和颈动脉粥样硬化情况,评价病变程度,对疾病的早期防治具有重要的价值.     

Associations of serum salusin-alpha levels with atherosclerosis and left ventricular diastolic dysfunction in essential hypertension

Serum salusin-alpha, is decreased in essential hypertension and acute coronary syndrome. The study is aimed to explore whether serum salusin-alpha is associated with atherosclerosis and left ventricular (LV) diastolic dysfunction in essential hypertension. Echocardiography, carotid ultrasonography, brachial-ankle pulse wave velocity (BaPWV) and serum salusin-alpha levels were determined in 60 hypertensive patients (29 with and 31 without carotid plaque) and 30 normotensive controls. Hypertensive patients with plaque, compared with those without plaque or the controls, had the lowest values of salusin-alpha. Then the hypertensive patients were divided into left ventricular hypertrophy (LVH) and non-LVH groups according to the echocardiography. Similarly, hypertensive patients with LVH showed the lowest serum salusin-alpha levels. In all subjects, serum salusin-alpha levels were negatively correlated with carotid mean-intima-media thickness (IMT), BaPWV, left ventricle mass index (LVMI) and E/E' (r=-0.488, P<0.001; r=-0.381, P<0.001; r=-0.294, P=0.006; r=-0.303, P=0.005; respectively). Serum salusin-alpha levels were independent predictors of BaPWV, carotid strain, carotid distensibility, mean-IMT, LVMI and E'/A' (β=-0.399, 0.283, 0.237, -0.346, -0.306, 0.469; P=0.002, 0.031, 0.016, 0.005, 0.012 and 0.001, respectively) in multiple linear regression models. These results suggest that serum salusin-alpha may be associated with atherosclerosis and LV diastolic dysfunction in essential hypertension.     

高血压伴颈动脉粥样硬化患者的动态血压

目的了解高血压伴颈动脉粥样硬化患者的动态血压变化。方法对186例高血压患者行超声检查双侧颈动脉,分成颈动脉正常组;颈动脉内膜增厚但无颈动脉斑块组和颈动脉内膜增厚有颈动脉斑块形成组。监测24h动态血压。结果颈动脉内膜增厚病人,无颈动脉斑块组和有颈动脉斑块组的最大收缩压、最小收缩压、平均收缩压、日间平均收缩压、夜间平均收缩压均高于颈动脉正常组,差异有统计学意义(P<0.05);无颈动脉斑块形成组和有颈动脉斑块形成组之间差异无统计学意义(P>0.05);最大舒张压、最小舒张压、平均舒张压、日间平均舒张压、夜间平均舒张压和全天平均动脉压在3组之间差异无统计学意义(P>0.05)。颈动脉内膜增厚病人组的异常昼夜节律的检出率和动态血压负荷值等于或超出40%的检出率高于颈动脉正常组。结论高血压患者动脉粥样硬化和有斑块患者的动态血压负荷值增大和昼夜节律异常。     

Serum vaspin levels are positively associated with carotid atherosclerosis in a general population

Objectives

Vaspin is a novel adipocytokine with potential insulin-sensitizing properties. Insulin resistance (IR) plays a role in the development and progression of atherosclerosis. However, the relationship between serum vaspin levels and atherosclerosis remains unknown. Therefore, we investigated whether vaspin was correlated with carotid intima-media thickness (c-IMT).

Methods

Data for fasting vaspin levels of 201 subjects (78 men and 123 women aged over 40 years) were obtained from a general population in Japan. We obtained anthropometric parameters and blood chemistries, and calculated homeostasis model assessment-IR (HOMA-IR) index. C-IMT was measured by B-mode ultrasonography. The mean values of each parameter by tertiles of vaspin were compared with analysis of variance, and the associations of vaspin with IR and c-IMT were evaluated by multiple stepwise regression analysis.

Results

Univariate analysis revealed that vaspin levels were positively correlated with BMI, insulin, HOMA-IR index, estimated glomerular filtration rate (eGFR), c-IMT and hypertensive medication. Multiple stepwise regression analysis revealed that HOMA-IR index, c-IMT and eGFR were significantly and independently associated with vaspin. We performed multivariate analyses with c-IMT as the dependent variable. Age, hypertensive medication and vaspin were significant for c-IMT. Moreover, a mediation analysis demonstrated that vaspin was significantly related to c-IMT, independently of IR.

Conclusions

The present study not only confirmed the previous finding of the positive association of vaspin with IR but also demonstrated that serum vaspin level was positively associated with c-IMT, independently of IR in a general population. Our results may suggest a role of vaspin in atherosclerosis in humans.     

Serum levels of substance P are decreased in patients with type 1 diabetes.

Morphological and immunohistochemical studies in diabetic subjects have shown a depletion of the neuropeptide substance P (SP) in the central and peripheral nervous system. This is the first study investigating serum levels of substance P in type 1 diabetes patients (n=50) and controls (n=75) by means of an enzyme immunoassay. The serum level of SP was significantly decreased in the diabetic group compared to the control group (10.12+/-0.29 vs. 12.25+/-0.38 pg/ml; p<0.0001). In diabetic patients, there was no correlation of substance P levels with age, serum creatinine, albuminuria, total cholesterol, HDL- or LDL-cholesterol, triglycerides, HbA1c, type or duration of diabetes and gender. Furthermore, there was no difference in serum levels of SP in patients with or without retinopathy, but SP was significantly decreased in patients with neuropathy (9.59+/-0.48 vs. 10.78+/-0.83 pg/ml; p=0.04). These data show that SP is decreased in serum of type 1 diabetes patients, especially in those with diabetic neuropathy. Subsequent and already ongoing prospective studies in well validated diabetic patients with neuropathy may characterize the impact of this neurogenic marker in the course of diabetic neuropathy.     

血清HB-EGF和SAA水平对高血压患者颈动脉粥样硬化的诊断价值

目的]研究血清肝素结合性表皮生长因子(HB-EGF)、血清淀粉样蛋白A(SAA)对高血压患者颈动脉粥样硬化(CAS)的诊断价值。 [方法]选取高血压患者100例,根据颈动脉内膜中膜厚度(CIMT)诊断结果将其分为高血压组(n＝42)、高血压CAS组(n＝58);另选取同期体检的健康受试者50例,设为健康对照组。比较健康对照组、高血压组和高血压CAS组血清HB-EGF、SAA水平及CIMT;采用Pearson相关分析法分析100例高血压患者血清HB-EGF、SAA水平与CIMT的相关性;采用Logistic回归分析法分析CAS的危险因素;采用ROC曲线分析血清HB-EGF、SAA水平对高血压患者CAS的诊断价值。 [结果]与健康对照组比较,高血压组和高血压CAS组血清HB-EGF、SAA水平显著升高(P＜0.05),CIMT显著增加(P＜0.05)。与高血压组比较,高血压CAS组血清HB-EGF、SAA水平显著升高(P＜0.05),CIMT显著增加(P＜0.05)。Pearson相关分析显示,血清HB-EGF、SAA水平与CIMT均表现为正相关(r＝0.807,95%CI:0.7257～0.8662,P＜0.001;r＝0.765,95%CI:0.6688～0.8357,P＜0.001)。Logistic回归分析显示,高HB-EGF、高SAA均是高血压患者发生CAS的危险因素(P＜0.05)。ROC曲线分析显示,血清HB-EGF、SAA水平诊断CAS的最佳截断点分别为19.84 μg/L、8.97 mg/L,两者单独及联合诊断CAS的AUC分别为0.811、0.810、0.875,两者联合诊断的价值高于单独诊断。 [结论]血清HB-EGF、SAA水平在高血压CAS患者中显著升高,两者与CIMT均为正相关,且对高血压CAS具有较高的诊断效能。     

Low-to-moderate atmospheric ozone levels are negatively correlated with hospital visits by asthma patients

Asthma is a chronic illness of the airways that affects approximately 300 million individuals worldwide. While it is commonly accepted that high ozone levels exacerbate asthma symptoms, the impact of low to moderate ozone levels on asthma symptoms has received little attention. The purpose of this research was to determine the relationship between hospital visits by asthma patients showing the severity of their symptoms and moderate ozone levels. Statistical analyses were performed on hospital visit big data for asthma patients in Seoul, Korea, collected between 2013 and 2017. The data set includes outpatient hospital visits (n = 17,787,982), hospital admissions (n = 215,696), and emergency department visits (n = 85,482). The frequency of hospital visits by asthma patients was evaluated in relation to low ozone levels (< 0.03 ppm) and moderate ozone levels (0.03–0.06 ppm) in the Seoul environment. In comparison to low ozone levels, moderate ozone levels resulted in a reduction in outpatient hospital visits (t = 7.052, P < .001). When ozone levels were low to moderate, there was a negative correlation between ozone levels and outpatient visits (r = −0.281, 95% CI: −0.331 to −0.228). Negative associations were also identified between ozone levels and new hospital admissions (t = 2.909, P < .01; r = −0.125, 95% CI: −0.179 to −0.070) and emergency treatments (t = 2.679, P < .01; r = −0.132, 95% CI: −0.186 to −0.076). Additionally, it was verified that moderate ozone levels one day before the visits resulted in a reduction in outpatient visits (t = 5.614, P < .001; r = −0.207, 95% CI: −0.259 to −0.153). A strong relationship was identified between moderate atmospheric ozone levels and a reduction in asthma patient hospital visits.     

Elevated endothelin-1 levels are associated with decreased arterial elasticity in hypertensive patients

Endothelin-1 stimulates collagen synthesis and is increased in hypertension, but its effect on collagen degradation remains unknown. The current study tested the hypothesis that elevated endothelin-1 levels are associated with decreased collagenase activity, markers of collagen degradation, and arterial compliance in hypertensive patients. Normotensive (n = 10) and hypertensive (n = 13) patients who were not on any antihypertensive medication were recruited, and small and large artery elasticity index, systemic vascular resistance, pulse pressure, and blood pressure were determined using blood pressure waveform analysis. Large artery elasticity index and collagen degradation products were decreased whereas endothelin-1, systemic vascular resistance, and pulse pressure were elevated in hypertensive patients. Plasma endothelin-1 was negatively correlated with a cross-linked C-terminal telopeptide of collagen type I, a collagen degradation marker (r = -0.43; p = 0.04), collagenase matrix metalloproteinase-1 (r = -0.48; p = 0.02), and large artery elasticity (r = -0.45; p = 0.03) and positively correlated with pulse pressure (r = 0.68; p = 0.0005). These results suggest that endothelin-1 contributes to decreased arterial compliance in hypertension via inhibition of collagen degradation.     

Short telomeres are associated with increased carotid atherosclerosis in hypertensive subjects

Recent studies have shown that individuals with shorter telomeres present a higher prevalence of arterial lesions and higher risk of cardiovascular disease mortality. As a group, patients with high blood pressure are at an increased risk for cardiovascular diseases. However, some hypertensive patients are more prone than others to atherosclerotic lesions. The main objective of this study was to examine the relationship between telomere length, as expressed in white blood cells, and carotid artery atherosclerotic plaques in hypertensive males. Data from 163 treated hypertensive men who were volunteers for a free medical examination were analyzed. Extracranial carotid plaques were assessed with B-mode ultrasound. Telomere length was measured from DNA samples extracted from white blood cells. The results of this study show that telomere length was shorter in hypertensive men with carotid artery plaques versus hypertensive men without plaques (8.17+/-0.07 kb versus 8.46+/-0.07 kb; P<0.01). Multivariate analysis showed that in addition to age, telomere length was a significant predictor of the presence of carotid artery plaques. The findings from this study suggest that in the presence of chronic hypertension, which is a major risk factor for atherosclerotic lesions, shorter telomere length in white blood cells is associated with an increased predilection to carotid artery atherosclerosis.     

Circulating thrombomodulin levels are related to latent progression of atherosclerosis in hypertensive patients.

The present study was designed to test the hypothesis that circulating levels of thrombomodulin are elevated in patients with hypertension in proportion to the severity of the vascular damage. A cross-sectional study was carried out using a population consisting of 96 patients with essential hypertension without clinically evident cardiovascular disease (mean age: 65 +/- 10 years) and 99 healthy normotensive control subjects (64 +/- 9 years). Blood was sampled and serum concentrations of soluble thrombomodulin were measured using an enzyme immunoassay method. We calculated the ratio of the concentration of thrombomodulin to that of creatinine, because soluble thrombomodulin is excreted by the kidney and the serum level of thrombomodulin was correlated with that of creatinine (p < 0.05). The association between the ratio and other clinical variables was investigated. The ratio of the thrombomodulin to creatinine concentrations was higher in hypertensive (29.3 +/- 10.9) than in control subjects (24.4 +/- 5.9; p < 0.0001). Systolic blood pressure was correlated with the ratio but the ratio showed no correlation with serum lipid levels when analyzed using data from all subjects. In hypertensive patients, the ratio correlated with the grade of sclerotic, but not hypertensive, changes in the fundus oculi (Scheie's classification, p < 0.001). Furthermore, the ratio correlated with brachial-ankle pulse wave velocity (p < 0.001). However, no correlation was detected between the ratio and blood pressure. These results suggest that circulating levels of thrombomodulin are elevated in hypertensive patients as compared to normotensive subjects and that the thrombomodulin level may be a molecular marker of the latent progression of atherosclerosis in hypertensive patients.     

Low testosterone levels are associated with carotid atherosclerosis in men

Objective. To study the relationship between endogenous sex hormone levels and intima‐media thickness (IMT) of the carotid artery measured by ultrasonography. Design. Population‐based cross‐sectional study. Methods. Sex hormone levels measured by immunoassay, anthropometric measurements and IMT was studied in 1482 men aged 25–84 years participating in the 1994–1995 Tromsø study. The data were analysed with partial correlation, multiple linear regression and logistic regression analysis. Results. Linear regression models showed that total testosterone and sex hormone‐binding globulin levels, but not calculated free testosterone, serum oestradiol or dehydroepiandrosterone sulphate levels were inversely associated with the age‐adjusted IMT (P = 0.008 and P < 0.001 respectively). These associations were independent of smoking, physical activity, blood pressure and lipid levels, but were not independent of body mass index (BMI). Excluding men with cardiovascular disease (CVD) did not materially change these results. In a logistic regression model adjusted for the confounding effect of CVD risk factors, men with testosterone levels in the lowest quintile (<9.0 nmol L^?1) had an independent OR = 1.51 (P = 0.015) of being in the highest IMT quintile. Conclusions. We found an inverse association between total testosterone levels and IMT of the carotid artery in men that was present also after excluding men with CVD, but was not independent of BMI. The clinical relevance of this, however, is uncertain and needs to be investigated in a clinical setting.     

Mildly elevated serum total bilirubin levels are negatively associated with carotid atherosclerosis among elderly persons with type 2 diabetes

Diabetes is strongly associated with several mechanisms of tissue damage such as oxidative stress. Serum bilirubin may have a beneficial role in preventing oxidative changes in cardiovascular disease (CVD). Limited information is available on whether serum bilirubin is an independent confounding factor for carotid atherosclerosis among elderly persons with type 2 diabetes. The study subjects were 169 men aged 79?±?8 (mean?±?SD) years and 205 women aged 81?±?8 years that were enrolled consecutively from patients in the medical department. Carotid intima-media thickness (IMT) and plaque were derived via B-mode ultrasonography. Multiple linear regression analysis showed that serum total bilirubin (β?=??0.160) was significantly associated with carotid IMT. Compared to subjects with a serum total bilirubin of tertile-1 (0.13–0.58?mg/dL), the multivariate-adjusted odds ratio (95% confidence interval) of carotid IMT ≥1.0?mm including plaque and carotid plaque was 0.46 (0.23–0.93) and 0.32 (0.17–0.60) in the Tertile-3 group (0.87–1.93?mg/dL), respectively. Next, data were further stratified by gender, age, smoking status, medication and prevalence of CVD. There were no significant differences in serum total bilirubin levels between selected subgroups. Our data demonstrated a negative association between serum total bilirubin and carotid atherosclerosis among elderly persons with type 2 diabetes.     

阿托伐他汀在高血压合并颈动脉粥样硬化患者中的作用

目的:探讨阿托伐他汀在高血压病患者合并颈动脉粥样硬化患者中的作用。方法:182例高血压病2级伴颈动脉粥样硬化患者随机分为阿托伐他汀组(91例)和对照组(91例),两组均给予高血压病标准治疗,他汀组在标准治疗上加用阿托伐他汀片,分别观察不同治疗时期脑梗塞的发生率。结果:阿托伐他汀治疗组3个月内脑梗塞发生率与对照组比较无显著差异(1.1%∶2.2%,P0.05),2年内脑梗塞发生率明显低于对照组(2.2%∶9.9%,P0.05)。结论:阿托伐他汀具有稳定动脉粥样斑块,改善血管内皮功能状态的作用,其在改善脑梗塞患者长期预后方面具有积极作用。     

Serum levels of Apelin-36 are decreased in older hospitalized patients with heart failure

PurposeApelin is an endogenous peptide, it is a potent inotropes, a peripheral vasodilator, involved in fluid homeostasis, balancing the harmful effects of Ang-II-AT1 system. The apelin-APJ axis is down regulated in chronic heart failure (CHF), but the role of apelin has not yet been studied in elderly patients with CHF. The aim of our study is to investigate serum levels of apelin-36 in a group of older subjects with CHF.Subjects/Materials and methodsThe study population consisted of 30 consecutive patients aged 80 ± 7.8 years with CHF. Serum apelin levels were quantified by enzyme immunoassay (ELISA). Results were considered significant if P was < 0.05.ResultsMean values of apelin-36 in CHF patients were 0.47 ± 0.21 ng/mL, and 0.95 ± 0.37 ng/mL in control subjects (P < 0.0001). Patients in IV NYHA class showed lower levels of apelin (0.38 ± 0.16 ng/mL). Direct correlations between apelin levels and ADLs (P = 0.0008, r = 0.61), and IADLs (P = 0.008, r = 0.50) were observed.Discussion and conclusionsThis study confirms that apelin levels are decreased in patients with CHF, also in the elderly and frail; since apelin represents a potential, promising novel therapeutic target for patients with CHF, geriatric patients should be considered for future clinical trials.     

Serum levels of bone resorption markers are decreased in patients with type 2 diabetes

Previous studies of bone turnover markers in diabetes are limited, and the results are conflicting. Our aim was to evaluate differences in bone turnover markers and i-PTH between T2DM and non-diabetes subjects. Cross-sectional study including 133 subjects (78 T2DM, 55 without diabetes). BMD were measured by dual X-ray absorptiometry. Bone turnover markers were determined in serum. Serum levels of bone resorption markers (CTX and TRAP5b) were lower in T2DM compared with non-diabetes subjects. There were no differences in bone formation markers. i-PTH serum levels were lower in T2DM: 38.35 ± 18.20 pg/ml versus 50.22 ± 18.99 pg/ml, P < 0.05. TRAP5b and CTX were positively correlated with i-PTH (CTX: r = 0.443, P < 0.001; TRAP5b: r = 0.180, P = 0.047). There was an inverse relationship between TRAP5b levels and diabetes duration (r = ?0.269, P = 0.021). T2DM patients have lower levels of bone resorption markers, and i-PTH compared with subjects without diabetes. Lower levels of PTH may induce a low turnover state as reflected by lower levels of bone resorption markers, and this situation may influence the higher risk of fracture of T2DM.