Leptin and adiponectin, but not IL18, are related with insulin resistance in treated HIV-1-infected patients with lipodystrophy

Leptin, adiponectin and IL18 are adipokines related with obesity, insulin resistance and dyslipidemia in the general population. Treated HIV-1-infected patients with lipodystrophy may develop insulin resistance and proatherogenic dyslipidemia. We assessed the relationship between plasma adipokine levels, adipokine genetics, lipodystrophy and metabolic disturbances. Plasma leptin, adiponectin and IL18 levels were assessed in 446 individuals: 282 HIV-1-infected patients treated with antiretroviral drugs (132 with lipodystrophy and 150 without) and 164 uninfected controls (UC). The LEP2410A>G, LEPRQ223R, ADIPQ276G>T, ADIPOR2-Intron5A>G and IL18-607C>A polymorphisms were validated by sequencing. Leptin levels were higher in UC than in HIV-1-infected, either with or without lipodystrophy (p<0.001 for both comparisons) and were lower in patients with lipodystrophy compared with those without lipodystrophy (p=0.006). In patients with lipodystrophy, leptin had a positive correlation with insulin and with HOMA-IR. Adiponectin levels were non-significantly different in UC and HIV-1-infected patients. Patients with lipodystrophy had lower adiponectin levels than non-lipodystrophy subjects (p<0.001). In patients with lipodystrophy, adiponectin was negatively correlated with insulin, HOMA-IR and triglycerides. Plasma IL18 levels were higher in HIV-1-infected patients compared with UC (p<0.001), and no differences were found according to the presence of lipodystrophy. In patients with lipodystrophy there was a negative correlation between IL18 levels and LDLc. Genetic analyses indicated no significant associations with lipodystrophy nor with insulin resistance or with lipid abnormalities. In conclusion, HIV-1-infected patients have reduced plasma leptin levels. This reduction is magnified in patients with lipodystrophy whose adiponectin levels were lower than that of non-lipodystrophy subjects. Plasma IL18 levels are increased in infected patients irrespective of the presence of lipodystrophy. The polymorphisms assessed are not associated with lipodystrophy or metabolic disturbances in treated HIV-1-infected patients.     

Elevated white blood cell count, CRP and fibrinogen levels are not associated with increased anti-endothelial and anti-ox-LDL antibody, MCP-1, and RANTES levels in early onset occlusive carotid artery disease

BACKGROUND: Inflammatory processes have importance in atherosclerosis. We evaluated if subjects below 55 years of age with occlusive carotid artery disease have higher serum levels of antibodies against oxidized LDL and endothelial cells and the chemokines MCP-1 and RANTES than age matched subjects without atherosclerosis. METHODS AND RESULTS: Sixty patients with occlusive carotid artery disease (stenosis or occlusion) and 30 age-matched controls participated in the study. We measured the degree of carotid artery stenosis and intima-media thickness (IMT) by duplex ultrasound. White blood cell count (WBC), C-reactive protein (CRP), and fibrinogen levels were significantly higher in patients (means+/-SD: 7.5+/-1.8 vs. 6.1+/-1.1 G/L, p<0.001; 7.7+/-20.7 vs. 2.5+/-1.9 mg/L, p=0.015; and 3.7+/-0.9 vs. 3.1+/-0.5 g/L, p<0.001, respectively). Antibody levels against oxidized LDL and endothelial cells (21.1+/-22.9 and 19.9+/-15.3 EU/mL, p=0.6; and 19+/-15 vs. 20+/-9 U/mL, p=0.07) and RANTES and MCP-1 levels (72.4+/-32.3 vs. 73.8+/-27.3 ng/mL, p=0.7; and 468+/-1041 vs. 318+/-131 pg/mL, p=0.7) did not differ significantly between patients and controls and did not correlate with IMT. CONCLUSIONS: Higher levels of WBC, CRP, and fibrinogen suggest an ongoing inflammation in early-onset carotid atherosclerosis, but increased IMT is not associated by the elevation of serum levels of chemokines and antibodies evaluated in this study.     

急性脑出血患者颈动脉斑块与血清hs CRP 及HbAlc的相关性研究

目的:探究急性脑出血患者颈动脉斑块与血清超敏C反应蛋白(hs-CRP)及糖化血红蛋白(Hb Alc)的相关性。方法:随机选取我院2013年5月至2015年1月脑科收治的急性脑出血患者84例,根据颈动脉粥样硬化标准将所有患者分为单纯脑出血组(n=25)、轻度粥样硬化组(n=34)和重度粥样硬化组(n=25)三组,另选取同期我院健康体检者50人(对照组)。对比分析四组颈总动脉膜厚度(IMT)空腹血糖(FPG)、三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、hs-CRP与Hb Alc水平,分析急性脑出血患者颈动脉斑块的危险因素。结果:四组的IMT、TC、TG、HDL、LDL、hs-CRP和Hb Alc水平差异均具有统计学意义(P0.05),其中hs-CRP和Hb Alc水平在单纯脑出血组轻度粥样硬化组重度粥样硬化组(P0.05);IMT与hs-CRP和Hb Alc均呈现正相关(r=0.388、0.420,P0.05);IMT、hs-CRP和Hb Alc均为颈动脉粥样硬化的危险因素(OR=3.065、1.978、1.647,P0.05)。结论:急性脑出血患者体内hs-CRP及Hb Alc水平是颈动脉斑块形成的危险因素。     

Circulating oxidized low-density lipoprotein and common carotid artery intima-media thickness in a random sample of middle-aged men

Circulating oxidized low-density lipoprotein (oxLDL) has been suggested to play an important role in atherosclerosis development. According to previous observations, oxLDL correlates with clinically manifest coronary and carotid artery disease. We investigated the association between the oxLDL concentration measured directly in plasma and common carotid artery intima-media thickness (IMT) in a population-based, case-control study in middle-aged men from Southern Finland. oxLDL was determined in 214 men by a commercially available sandwich ELISA test (Mercodia). Carotid artery IMT was measured at 12 standardized segments by B-mode ultrasonography (at the near and far wall of the left and right common carotid arteries, bifurcations and internal carotid arteries), and the overall mean maximum IMT (MMaxIMT) was calculated. The MMaxIMT of the carotid arteries was significantly associated with circulating oxLDL (r_s=0.16, p=0.018). In a stepwise multiple regression model with MMaxIMT as dependent variable and systolic blood pressure, smoking, oxLDL, HDL cholesterol and apolipoprotein B as covariates, systolic blood pressure (=0.22, p<0.001), oxLDL (=0.15, p=0.022) and smoking (=0.17, p=0.014) showed an independent association with IMT (R²=0.10, p<0.001). Our results show that oxLDL measured directly from plasma is independently associated with subclinical carotid artery atherosclerosis in middle-aged men.     

不同血液净化方法对维持性血液透析尿毒症动脉粥样硬化患者血清microRNA-144和microRNA-155水平的影响及其临床意义

摘要 目的：探讨不同血液净化方法对维持性血液透析（MHD）尿毒症动脉粥样硬化患者血清microRNA-144和microRNA-155水平的影响及其临床意义。方法：选取2019年6月~2020年6月川北医学院附属医院收治的98例MHD尿毒症动脉粥样硬化患者为研究组,另选取98例同期本院体检健康的志愿者为健康对照组,比较两组血清microRNA-144和microRNA-155、血清炎症因子[白细胞介素-6（IL-6）、单核细胞趋化蛋白-1（MCP-1）、超敏C反应蛋白（hs-CRP）]水平。采用Pearson分析法分析血清microRNA-144、microRNA-155水平与MHD尿毒症动脉粥样硬化患者内膜中层厚度（IMT）值、斑块面积及血清炎症因子的相关性。采用多因素Logistic回归分析MHD尿毒症动脉粥样硬化患者IMT增厚的影响因素。将研究组按随机数字表法分为血液透析滤过组和血液灌流组,各49例。血液透析滤过组给予血液透析滤过联合血液透析治疗,血液灌流组给予血液灌流联合血液透析治疗。比较两组血清microRNA-144和microRNA-155、血清炎症因子水平、IMT值和斑块面积。结果：研究组血清microRNA-144、microRNA-155、IL-6、MCP-1、hs-CRP水平明显高于健康对照组（P<0.05）;Pearson相关性结果显示,血清microRNA-144、microRNA-155均与MHD尿毒症动脉粥样硬化患者IMT值、斑块面积及IL-6、MCP-1、hs-CRP均呈正相关（P<0.05）;多因素Logistic回归分析结果显示,血清microRNA-144、microRNA-155、IL-6、MCP-1、hs-CRP水平均是导致MHD尿毒症动脉粥样硬化患者IMT增厚的危险因素（P<0.05）。治疗后,血液灌流组血清microRNA-144和microRNA-155水平均明显低于血液透析滤过组（P<0.05）,IL-6、MCP-1、hs-CRP水平均明显低于血液透析滤过组（P<0.05）,IMT值和斑块面积均明显低于血液透析滤过组（P<0.05）。结论：血清microRNA-144、microRNA-155水平与IMT值、斑块面积及IL-6、MCP-1、hs-CRP水平呈正相关,均是MHD尿毒症动脉粥样硬化患者IMT增厚的危险因素。血液灌流联合血液透析治疗可减轻机体炎症反应,延缓动脉粥样硬化进程,可能与下调患者血清microRNA-144、microRNA-155水平有关。     

Plasma lecithin:cholesterol acyltransferase and carotid intima-media thickness in European individuals at high cardiovascular risk

Lecithin:cholesterol acyltransferase (LCAT) is the enzyme responsible for cholesterol esterification in plasma. LCAT is a major factor in HDL remodeling and metabolism, and it has long been believed to play a critical role in macrophage reverse cholesterol transport (RCT). The effect of LCAT on human atherogenesis is still controversial. In the present study, the plasma LCAT concentration was measured in all subjects (n = 540) not on drug treatment at the time of enrollment in the multicenter, longitudinal, observational IMPROVE study. Mean and maximum intima-media thickness (IMT) of the whole carotid tree was measured by B-mode ultrasonography in all subjects. In the entire cohort, LCAT quartiles were not associated with carotid mean and maximum IMT (P for trend 0.95 and 0.18, respectively), also after adjustment for age, gender, HDL-cholesterol (HDL-C), and triglycerides. No association between carotid IMT and LCAT quartiles was observed in men (P=0.30 and P=0.99 for mean and maximum IMT, respectively), whereas carotid IMT increased with LCAT quartiles in women (P for trend 0.14 and 0.019 for mean and maximum IMT, respectively). The present findings support the concept that LCAT is not required for an efficient reverse cholesterol transport and that a low plasma LCAT concentration and activity is not associated with increased atherosclerosis.     

Association of APOE genotype with carotid atherosclerosis in men and women: the Framingham Heart Study

The aim of this study was to determine the association between APOE genotype and carotid atherosclerosis, defined as intimal-medial thickness (IMT) and stenosis, and to assess if other cardiovascular risk factors modify this association. A total of 1,315 men and 1,408 women from the Framingham Offspring Study underwent carotid ultrasound during examination cycle 6 and had complete data on APOE genotype. Three APOE genotype groups were defined: APOE2 (including E2/E2, E3/E2 genotypes), APOE3 (E3/E3), and APOE4 (including E4/E3, E4/E4 genotypes). Carotid IMT and the presence of carotid stenosis > 25% were determined by ultrasonography. In women, the APOE2 group was associated with lower carotid IMT (0.67 vs. 0.73 mm) and lower prevalence of stenosis (odds ratio = 0.49; 95% confidence interval = 0.30-0.81) compared with the APOE3 group. In men, APOE genotype was not associated with carotid IMT or stenosis in the whole group; however, diabetes modified the association between APOE genotype and carotid IMT (P for interaction = 0.044). Among men with diabetes, the APOE4 group was associated with a higher internal carotid artery IMT (1.22 mm) than the APOE3 group (0.90 mm) or the APOE2 group (0.84 mm). The E2 allele was associated with lower carotid atherosclerosis in women, and the E4 allele was associated with higher internal carotid IMT in diabetic men.     

The metabolic syndrome and progression of carotid atherosclerosis over 13 years. The Tromso study

ABSTRACT: BACKGROUND: The metabolic syndrome (MetS) is associated with increased risk of cardiovascular disease. In this study, we examine if metabolic syndrome predicts progression of atherosclerosis over 13 years. METHODS: Participants were 1442 men and 1532 women in the population-based Tromso Study who underwent carotid ultrasound examinations at baseline in the 4th (1994-5) and at follow-up in the 6th survey (2007-8). Of these, 278 men and 273 women fulfilled the criteria for the MetS, defined according to a modified version of the National Cholesterol Education Program Adult Treatment Panel III (NCEP, ATPIII). Carotid atherosclerosis was assessed as total plaque area (TPA) and mean intima-media thickness (IMT) at follow-up and as change in IMT and TPA from baseline to follow-up. Associations between MetS and its components and carotid atherosclerosis were assessed in linear regression models adjusted for age, total cholesterol and daily smoking, stratified by sex. RESULTS: IMT and TPA levels at follow-up (p < 0.0001) and progression of TPA (p = 0.02) were higher in the MetS group compared to the non-MetS group. In stepwise multivariable models, MetS was associated with TPA (beta = 0.372 mm2, p = 0.009) and IMT (beta = 0.051 mm, p < 0.0001) in men, and with IMT (beta = 0.045 mm, p = 0.001) in women after 13 years of follow-up, but not with progression of IMT or TPA. In analyses stratified by age, MetS predicted progression of IMT (beta = 0.043 mm, p = 0.046) and TPA (beta = 1.02 mm2, p = 0.002) in men below 50 years of age. Hypertension was predictive of follow-up TPA and IMT in both genders and of progression of TPA in women. Impaired glucose tolerance was associated with follow up levels of IMT and TPA as well as progression in IMT in men. None of the other components of MetS were associated with progression of atherosclerosis. CONCLUSIONS: Subjects with MetS had higher levels of IMT and TPA at follow up than those without MetS. Mets predicted progression of IMT and TPA in those below 50 years of age, but not in other age groups, indicating that MetS may be involved in the initiation of the atherosclerotic process.     

Intima media thickness of common carotid arteries is associated with traditional risk factors and presence of ischaemic heart disease in hemodialysis patients

Patients with chronic renal failure are prone to cardiovascular complications. The mechanisms and the assessment of the risk of cardiovascular diseases (CVD) in this population are of interest. The purpose of this study was to investigate the traditional and potential risk factors for the development of CVD and their contribution to ischemic heart disease (IHD) and variation in carotid intima media thickness (IMT) in hemodialyzed patients (HD). Twenty-one chronically HD patients and nineteen healthy volunteers were recruited. Studied parameters were intima-media thickness, body mass index (BMI), mean arterial blood pressure (MAP), hemoglobin, fibrinogen (Fbg), serum lipids, lipoprotein (a) [Lp(a)], total homocysteine (tHcy). Mean carotid IMT, tHcy, Fbg and Lp(a) were higher in HD patients compared to the control group. There were no differences in cholesterol (tCh) and triglycerides between these groups. Patients with ischemic heart disease were older and they had higher values of carotid IMT, tCh, triglycerides, Fbg and Lp(a). There were no differences in MAP, time on dialysis and tHcy between the two subgroups (with vs without IHD). Carotid IMT correlated positively with age (r = 0.68, p = 0.001), BMI (r = 0.50, p = 0.02), tCh (r = 0.58, p < 0.01), LDL- cholesterol (r = 0.55, p = 0.01) and Fbg (r = 0.57, p < 0.01) but not with tHcy or Lp(a) in the patients group. Carotid intima media thickness thus reflects the risk for ischemic heart disease in hemodialyzed patients. Elevated fibrinogen concentration and dyslipidemia influence arterial remodelling.     

Ultrasound settings significantly alter arterial lumen and wall thickness measurements

Background

Arterial diameter and intima-media thickness (IMT) enlargement may each be related to the atherosclerotic process. Their separate or combined enlargement may indicate different arterial phenotypes with different atherosclerosis risk.

Methods

We investigated cross-sectional (baseline 1987–89: n = 7956) and prospective (median follow-up = 5.9 years: n = 4845) associations between baseline right common carotid artery (RCCA) external diameter and IMT with existing and incident carotid atherosclerotic lesions detected by B-mode ultrasound in any right or left carotid segments. Logistic regression models (unadjusted, adjusted for IMT, or adjusted for IMT and risk factors) were used to relate baseline diameter to existing carotid lesions while comparably adjusted parametric survival models assessed baseline diameter associations with carotid atherosclerosis progression (incident carotid lesions). Four baseline arterial phenotypes were categorized as having 1) neither IMT nor diameter enlarged (reference), 2) isolated IMT thickening, 3) isolated diameter enlargement, and 4) enlargement of both IMT and diameter. The association between these phenotypes and progression to definitive carotid atherosclerotic lesions was assessed over the follow-up period.

Results

Each standard deviation increment of baseline RCCA diameter was associated with increasing carotid lesion prevalence (unadjusted odds ratio [OR] = 1.54, 95% confidence interval [CI] = 1.47–1.62) and with progression of carotid atherosclerosis (unadjusted hazards ratio (HR) = 1.37, 95% CI = 1.28–1.46); and the associations remained significant even after adjustment for IMT and risk factors (prevalence OR = 1.11, 95% CI = 1.04–1.18; progression HR = 1.11, 95% CI = 1.03–1.19). Controlling for gender, age and race, persons with both RCCA IMT and diameter in the upper 50^th percentiles had the greatest risk of progressing to clearly defined carotid atherosclerotic lesions (all HR = 1.71, 95% CI = 1.47–2.0; men HR = 1.88, 95% CI = 1.48–2.39; women HR = 1.59, 95% CI = 1.31–1.95) while RCCA IMT or diameter alone in the upper 50^th percentile produced significantly lower estimated risks.

Conclusion

RCCA IMT and external diameter provide partially overlapping information relating to carotid atherosclerotic lesions. More importantly, the RCCA phenotype of coexistent wall thickening with external diameter enlargement indicates higher atherosclerotic risk than isolated wall thickening or diameter enlargement.     

Carotid Atherosclerotic Disease Predicts Cardiovascular Events in Hemodialysis Patients: A Prospective Study

Background

To evaluate the predictive value of carotid atherosclerotic disease (CAD) and intima-media thickness (IMT) on incident cardiovascular disease and mortality in hemodialysis patients.

Methods

Multicenter, observational, prospective study including 110 patients, followed-up to 6 years. Carotid doppler ultrasonographic findings were classified in 4 degrees of severity: 1) IMT <0.9 mm, 2) IMT >0.9 mm, 3) carotid plaque with stenosis <50% and 4) plaque with stenosis >50%. The associations between IMT and CAD and cardiovascular events, total and cardiovascular mortality were assessed.

Results

83% of the patients had atherosclerotic plaques (CAD degrees 3-4). During follow-up, 29.1% of patients experienced cardiovascular events, and 28.2% died, 38.7% of cardiovascular origin. The presence of plaques was associated with cardiovascular events (p = 0.03) while calcified plaques were associated with both cardiovascular events (p = 0.01), cardiovascular mortality (p = 0.03) and non-significantly with overall mortality (p = 0.08) in the survival analysis. Carotid IMT was not associated with outcomes. Cardiovascular events correlated with CAD severity (HR 2.27, 95% CI 1.13-4.54), age (HR 1.04, 1.01-1.06), previous cardiovascular disease (HR 1.75, 1.05-4.42), dyslipidemia (HR 2.25, 1.11-4.53), lipoprotein (a) (HR 1.01, 1.00-1.02), troponin I (HR 3.89, 1.07-14.18), fibrinogen levels (HR 1.38, 0.98-1.94) and antiplatelet therapy (HR 2.14, 1.04-4.4). In an age-adjusted multivariate model, cardiovascular events were independently associated with previous coronary artery disease (HR 3.29, 1.52-7.15) and lipoprotein (a) (HR 1.01, 1.00-1.02).

Conclusions

The presence of carotid plaques and, especially, calcified plaques, are predictors of new cardiovascular events and cardiovascular mortality in hemodialysis patients, while IMT was not. The prognostic value of calcified plaques should be confirmed in future studies.     

Influence of Visceral Obesity and Liver Fat on Vascular Structure and Function in Obese Subjects

Endothelial dysfunction and increased intima–media thickness (IMT) have been found in obese patients. Both regional fat distribution and liver steatosis may influence these markers of subclinical atherosclerosis. We sought to determine the interrelationships of endothelial function, carotid IMT, visceral and subcutaneous adipose tissue accumulation, and liver steatosis in severely obese subjects. In 64 severely obese patients (BMI 42.3 ± 4.3 kg/m²), we determined (i) endothelial function as flow‐mediated dilation (FMD) of the brachial artery, (ii) carotid IMT, (iii) visceral fat diameter, and (iv) degree of liver steatosis using ultrasound. FMD was associated inversely with visceral fat diameter and degree of steatosis (r = ?0.577, P < 0.0001 and r = ?0.523, P < 0.0001, respectively). Carotid IMT correlated with visceral fat mass (r = 0.343, P = 0.007) but not with liver steatosis. After adjustment for conventional cardiovascular risk factors, FMD was predicted independently by the visceral fat diameter, age, and sex (r² = 0.48, P < 0.0001), but not by the degree of liver steatosis or plasma adiponectin levels. In contrast, age and sex were the only predictors of IMT (r² = 0.33, P < 0.001). In obese patients, visceral fat diameter is a major determinant of endothelial dysfunction, independent of traditional risk factors or the degree of liver steatosis and plasma adiponectin. Measurement of visceral fat diameter by ultrasound is a novel and simple method to identify subjects with an increased risk for atherosclerosis within an obese population.     

Uridine metabolism in HIV-1-infected patients: effect of infection, of antiretroviral therapy and of HIV-1/ART-associated lipodystrophy syndrome

Background

Uridine has been advocated for the treatment of HIV-1/HAART-associated lipodystrophy (HALS), although its metabolism in HIV-1-infected patients is poorly understood.

Methods

Plasma uridine concentrations were measured in 35 controls and 221 HIV-1-infected patients and fat uridine in 15 controls and 19 patients. The diagnosis of HALS was performed following the criteria of the Lipodystrophy Severity Grading Scale. Uridine was measured by a binary gradient-elution HPLC method. Analysis of genes encoding uridine metabolizing enzymes in fat was performed with TaqMan RT-PCR.

Results

Median plasma uridine concentrations for HIV-1-infected patients were 3.80 µmol/l (interquartile range: 1.60), and for controls 4.60 µmol/l (IQR: 1.8) (P = 0.0009). In fat, they were of 6.0 (3.67), and 2.8 (4.65) nmol/mg of protein, respectively (P = 0.0118). Patients with a mixed HALS form had a median plasma uridine level of 4.0 (IC95%: 3.40–4.80) whereas in those with isolated lipoatrophy it was 3.25 (2.55–4.15) µmol/l/l (P = 0.0066). The expression of uridine cytidine kinase and uridine phosphorylase genes was significantly decreased in all groups of patients with respect to controls. A higher expression of the mRNAs for concentrative nucleoside transporters was found in HIV-1-infected patients with respect to healthy controls.

Conclusions

HIV-1 infection is associated with a decrease in plasma uridine and a shift of uridine to the adipose tissue compartment. Antiretroviral therapy was not associated with plasma uridine concentrations, but pure lipoatrophic HALS was associated with significantly lower plasma uridine concentrations.     

The importance of indicators of the initial phase of atherosclerosis in patients with microvascular angina

Endothelial dysfunction (ED) is generally considered to be the initial step in the progression to atherosclerosis but there is still much uncertainty about the role of the microvascular form of angina in patients with a normal coronary angiogram with regard to ED. The authors investigated the extent of endothelial perturbation and thereby whether the microvascular form of angina precedens macroscopic atherosclerosis by means of non-invasive ultrasound measurement of the intima-media thickening (IMT) in common carotid artery and flow mediated dilatation (FMD) in the brachial artery. 28 patients with stable angina with positive exercise test and ST segment depression (22 females, 6 males, average age 54 years) were compared with a control group consisting of 28 patients with no clinical signs of coronary artery disease (18 females, 10 males, average age 53 years). No significant difference in FMD% (7.3 vs. 10.8, p = 0.07) was found between the groups, though specific measurements (average dilatation of the brachial artery induced by ischemic insult, peak blood flow and peak hyperemic flow) differed considerably. Also IMT did not vary significantly between the groups (0.74 vs. 0.65, p = 0.08). In patients with IMT > 0.8 mm (6 patients in each group) a significant decrease of FMD was found as compared with patients with normal IMT (p < 0.05). It was concluded that in patients with increased IMT an inverse relationship between FMD and IMT exists both in patients with microvascular angina and in the healthy control subjects whereas in the group of patients with normal IMT no ED was demonstrated. This supports the hypothesis that the microvascular form of angina is the early stage of coronary artery atherosclerosis and this escapes angiographic recognition.     

Association between serum sulfatide and carotid intima media thickness in patients with familial hypercholesterolemia

There is a positive association between sulfatide and atherosclerosis in an animal model for human familial hypercholesterolemia. Carotid intima–media thickness (IMT) is thought to be a marker of atherosclerosis in humans. We investigated the relationship between sulfatide and carotid IMT in heterozygous familial hypercholesterolemia (FH) patients. Thirty-five genetically-verified heterozygous patients with FH and 34 healthy controls were recruited into our study. We measured serum sulfatide levels, the carotid IMT, and conventional cardiovascular risk factors including obesity parameters, blood pressure, fasting blood glucose, and lipid profiles. Subjects with heterozygous FH had significantly elevated serum sulfatide, elevated total cholesterol, low-density lipoprotein cholesterol, and increased carotid IMT compared with control subjects. In patients with FH, univariate analysis showed that serum sulfatide was significantly correlated with carotid IMT. Multiple linear regression analysis indicated that serum sulfatide was the only independent predictor of carotid IMT in patients with FH. Patients with heterozygous FH had significantly higher carotid IMT and the level of serum sulfatide was independently associated with atherosclerotic progression. (R: 0.720, R²: 0.503, p?相似文献   

Long-Term BMI changes since adolescence and markers of early and advanced subclinical atherosclerosis

Although long‐term weight gain has been associated with cardiovascular risk and intima‐media thickening (IMT), no sufficient data exist on possible associations of such weight changes with more advanced stages of subclinical atherosclerosis. Moreover, the value of self‐reported weight changes, a more practical approach to assess long‐term history in adiposity status, is still a matter of debate. In this longitudinal study, long‐term changes in BMI and overweight status were assessed in 106 healthy young adults (age 40.5 ± 1.1 years, 60 males). These were a subgroup of adolescent school students who had originally been examined in 1983 initially aiming to assess cardiovascular risk factor prevalence. Markers of early (carotid IMT) and advanced (presence of plaques in the carotid and femoral arteries and ankle‐brachial index, ABI) subclinical atherosclerosis were measured in all individuals. By multivariate analysis, among other risk factors, IMT and the presence of plaques were independently determined by BMI change, while a low ABI was also determined by changes in overweight status. An adverse long term adiposity profile change (≥ +4 kg/m² and/or change into overweight/obese status from normal weight since adolescence) incrementally determined a low ABI over current risk factors. Self‐reported and actual BMI changes were correlated (r = 0.587) but their means significantly differed, while the former significantly correlated with IMT only (P = 0.032). In conclusion, an adverse long term adiposity status change was more prominently associated with advanced subclinical atherosclerosis and particularly low ABI. These results also suggest that the utility of self‐reported weight changes may be limited in primary prevention practice.     

Soluble cell adhesion molecules s-VCAM-1 and s-ICAM-1 in subjects with familial combined hyperlipidemia

Familial combined hyperlipidemia (FCH) is the most common familial hyperlipidemia with a high risk for early atherosclerosis. The aim of this study was to compare levels of soluble intercellular cell adhesion molecule 1 (s-ICAM-1) and soluble vascular cell adhesion molecule 1 (s-VCAM-1) in asymptomatic members of FCH families with healthy controls and to determine the relation between s-ICAM-1, s-VCAM-1 and risk factors accompanying FCH. We also investigated the association between adhesion molecules and the intima-media thickness (IMT) of the common carotid artery, a recognized morphological marker of early atherosclerosis. 82 members of 29 FCH families were divided into the 2 groups: HL (probands and hyperlipidemic first-degree relatives, n = 47) and NL (normolipidemic first-degree relatives, n = 35). The control groups--HL-C (n = 20) and NL-C (n = 20)--consisted of sex- and age-matched healthy individuals. Hyperlipidemic members had significantly higher concentration of s-ICAM-1 (633.7 +/- 169.6 ng/ml versus 546.2 +/- 155.9 ng/ml, p < 0.05). The elevation of s-VCAM-1 was not significant (880.8 +/- 202.9 ng/ml versus 826.5 +/- 174.6 ng/ml, N.S.). Levels of s-ICAM-1 and of s-VCAM-1 in normolipidemic relatives were not significantly different from the control group (530.8 +/- 113.9 ng/ml versus 530.0 +/- 101.0 ng/ml and 860.2 +/- 265.7 ng/ml versus 822.1 +/- 197.0 ng/ml respectively). There was a significant correlation between s-ICAM-1 and apoB (r = 0.42; p < 0.01) in hyperlipidemic subjects and between s-ICAM-1 and proinsulin (r = 0.54; p < 0.01) in normolipidemic subjects. S-ICAM-1 correlated with IMT (r = 0.32; p < 0.05) in all members of FCH families. The increase of s-ICAM-1 in asymptomatic hyperlipidemic members of FCH families reflects their high cardiovascular risk. The positive association between s-ICAM-1 and IMT could indicate s-ICAM-1 as a potential predictor of atherosclerosis manifestation.     

Comparison of human immunodeficiency virus (HIV)-specific T-cell responses in HIV-1- and HIV-2-infected individuals in Senegal

Human immunodeficiency virus type 2 (HIV-2) infection is typically less virulent than HIV-1 infection, which may permit the host to mount more effective, sustained T-cell immunity. We investigated antiviral gamma interferon-secreting T-cell responses by an ex vivo Elispot assay in 68 HIV-1- and 55 HIV-2-infected Senegalese patients to determine if differences relate to more efficient HIV-2 control. Homologous HIV-specific T cells were detected in similar frequencies (79% versus 76%, P = 0.7) and magnitude (3.12 versus 3.08 log(10) spot-forming cells/10(6) peripheral blood mononuclear cells) in HIV-1 and HIV-2 infection, respectively. Gag-specific responses predominated in both groups (>/=64%), and significantly higher Nef-specific responses occurred in HIV-1-infected (54%) than HIV-2-infected patients (22%) (P < 0.001). Heterologous responses were more frequent in HIV-1 than in HIV-2 infection (46% versus 27%, P = 0.04), but the mean magnitude was similar. Total frequencies of HIV-specific responses in both groups did not correlate with plasma viral load and CD4(+) T-cell count in multivariate regression analyses. However, the magnitude of HIV-2 Gag-specific responses was significantly associated with lower plasma viremia in HIV-1-infected patients (P = 0.04). CD4(+) T-helper responses, primarily recognizing HIV-2 Gag, were detected in 48% of HIV-2-infected compared to only 8% of HIV-1-infected patients. These findings indicate that improved control of HIV-2 infection may relate to the contribution of T-helper cell responses. By contrast, the superior control of HIV-1 replication associated with HIV-2 Gag responses suggests that these may represent cross-reactive, higher-avidity T cells targeting epitopes within Gag regions of functional importance in HIV replication.