Blood rheology as a contributing factor in reduced coronary reserve in systemic hypertension

The influence of blood fluidity on coronary reserve in patients with essential hypertension and normal coronary arteries was examined. The coronary reserve, expressed as the ratio of coronary vascular resistance under resting conditions to the coronary vascular resistance after administration of dipyridamole, was 4.1 +/- 1.5 in 10 normotensive patients with normal coronary arteries, whereas the mean value was only 2.4 +/- 0.8 in 35 hypertensive patients. When compared with the normotensive control group the 35 hypertensive patients had significantly higher levels of hematocrit (45.9 +/- 3.7 vs 42.3 +/- 3.6; p less than or equal to 0.01) and plasma viscosity (1.39 +/- 0.07 vs 1.32 +/- 0.06 mPas; p less than 0.01). Plasma fibrinogen (291 +/- 67 vs 251 +/- 25 mg/dl) and whole blood viscosity at a shear rate of 2 s-1 (7.77 +/- 1.1 vs 7.21 +/- 1.28 mPas) and at a high shear rate of 100 s-1 (4.23 +/- 0.57 vs 3.91 +/- 0.64 mPas) demonstrated a trend without statistical significance toward higher values in hypertensive patients. When the hypertensive group was further divided according to the coronary reserve (less than 2.5, severely impaired coronary reserve; greater than 2.5 less than 3.8, moderately impaired coronary reserve), the parameters of blood fluidity clearly correlated inversely with coronary reserve. This suggests a major importance of rheologic abnormalities on impaired coronary reserve in hypertensive patients.     

Blood rheology in patients with diabetes mellitus

Blood rheology is now receiving increasing attention as an important potential contributory factor to diabetic angiopathy. This study was designed to provide evidence for and against early hemorheological abnormalities in diabetes mellitus (DM). For this purpose, blood viscosity, RBC aggregation, hematocrit, and plasma protein's levels of both fibrinogen and albumin were measured in 86 uncomplicated patients with DM (45 type 1 and 41 type 2). Patients with HbA1c < 7.5% were considered as having good glycemic control (GGC), while those with HbA1c > 8.5% as having poor glycemic control (PGC). Patients with type 1 DM showed normal blood viscosity at both shear rates high and low, while native hematocrit, fibrinogen, and RBC aggregation were significantly elevated and albumin significantly reduced when compared with healthy volunteers. Patients with type 2 DM showed more marked impairments associated with an increased low shear rate blood viscosity, when compared with patients with type 1 DM. Comparison between two subgroups of patients, both of which with type 1 DM and of similar disease duration of <5 yrs, with GGC or PGC showed that impaired blood rheology does depend on the quality of glycemic control. Differences were attenuated after a disease duration of >15 yrs. These findings suggest that early hemorheological impairments in patients with type 1 DM are dependent upon the glycemic control. In contrast, hemorheological impairments appear to be inevitable after a mean disease duration of 15 yrs even if there is a GGC. Aggravation of hemorheological abnormalities in patients with type 2 DM might depend upon the hemorheological effects of other metabolic abnormalities related to insulin resistance rather than the quality of glycemic control.     

Blood rheology in men with essential hypertension and capillary rarefaction

The pathophysiological significance of hyperviscosity and capillary rarefaction in untreated essential hypertension is unknown. Fifty untreated hypertensive men with capillary rarefaction (intravital capillaroscopy) and 20 age- and sex-matched normotensive controls underwent full haemorheological profiling (blood viscosity at high and low shear, haematocrit, platelet and leukocyte counts, fibrinogen and total protein concentrations, P-selectin levels, erythrocyte and leukocyte filterability rates and erythrocyte deformability and aggregation indexes). Subjects with skin capillary density below the group median had younger age, higher diastolic pressure, higher blood viscosity at low shear, higher P-selectin levels, higher erythrocyte and leukocyte filterability rates, and higher erythrocyte aggregation indexes (all P < 0.01). In contrast, patients with greater skin capillary density had a greater plasma viscosity (P < 0.05). The conclusions were that in untreated hypertensive men, capillary rarefaction and hyperviscosity are associated to an increased diastolic blood pressure and to an adverse haemorheological profile.     

Selective microproteinuria as a marker of incipient renal impairment in patients with hypertension

Incidence of chronic renal failure has a worldwide tendency to growth. Hypertension occupies an important place among causes of this upward trend. That is why in patients with hypertension and incipient changes of the kidneys it seems most appropriate to use antihypertensive drugs with renoprotective properties. Early treatment with these drugs enables most effective lowering of risk of renal failure development and thus has a potential to prolong life of a patient. Selective microproteinuria is considered to be a marker of incipient renal impairement. Among groups of antihypertensive agents angiotensin converting enzyme inhibitors, angiotensin receptor blockers, calcium antagonists, beta-blockers, and diuretics have proven renoprotective properties.     

Circulating E-selectin as a risk marker in patients with end-stage renal disease

BACKGROUND: E-selectin is a key adhesion molecule which plays a fundamental role in endothelial progenitor cell-dependent reparative mechanisms in experimental ischaemia and it serves to anchor leucocytes to the endothelium in inflammatory processes. Inflammation is one of the strongest risk factors for death and cardiovascular (CV) events in end-stage renal disease (ESRD). OBJECTIVE: The objective of the current study was to evaluate whether E-selectin is a useful biomarker of clinical outcome in ESRD patients. We tested the prediction power of circulating E-selectin for mortality and CV events in a cohort of 265 ESRD patients. RESULTS: During the follow-up, 59 patients died and 58 had CV events. All-cause mortality was inversely related to serum E-selectin, the risk of death being the lowest in patients in the third E-selectin tertile (HR: 1, reference group), intermediate in those in the second tertile (HR: 1.30) and the highest in patients in the first tertile (HR: 2.02, P = 0.01). Similarly, the risk of fatal and nonfatal CV events followed an inverse pattern being lowest in the third tertile (reference group) and highest in the first tertile (HR: 1.73, P = 0.03). The prediction power of E-selectin for death and CV events was confirmed in a Cox regression analysis where E-selectin emerged as an inverse predictor of these outcomes, particularly so in patients with severe inflammation. CONCLUSIONS: These data are in keeping with the hypothesis that in systemic inflammation altered E-selectin shedding may play a role in arterial damage and implicates this adhesion molecule in atherosclerotic complications in a high-risk condition like ESRD.     

Studies on blood rheology in patients with primary pulmonary hypertension

The rheologic properties of blood were studied in 6 patients with primary pulmonary hypertension (PPH) and compared with those of a control group of 10 healthy subjects. Blood viscosity was studied with a rotational viscometer and blood cell deformability with a filtrometer giving values for clogging particles (CP) and red cell transit time (RCTT). Blood viscosity at varying shear rates was found to be increased both at natural (p less than 0.025-0.005) and standardized hematocrit, 45% (p less than 0.05 at 40 s-1) in patients with PPH. Red cell deformability was reduced as indicated by a significant increase of RCTT (p less than 0.01). Increased values for hematocrit (p less than 0.001), hemoglobin concentration (p less than 0.001), and erythrocyte count (p less than 0.005) were found and decreased values for mean corpuscular hemoglobin concentration (MCHC) (p less than 0.025) and HDL cholesterol (p less than 0.005). Plasma viscosity, white cell deformability, white cell count, mean corpuscular volume (MCV), and plasma fibrinogen concentration did not significantly differ from the values found in the control group. It is concluded that patients with PPH have impaired blood rheology. The hemorheologic abnormalities in these patients may be of hemodynamic significance.     

Brain natriuretic peptide as a preclinical marker of chronic pulmonary hypertension in patients with pulmonary embolism

Chronic thromboembolic pulmonary hypertension (CTPH) is a potential complication of pulmonary embolism (PE). Only few studies have assessed the role of brain natriuretic peptide (BNP) in patients with chronic pulmonary hypertension, and there are no data on the potential utility of BNP as a preclinical biomarker of CTPH. To assess the correlation between pulmonary artery systolic pressures (PAPs) and amino terminal proBNP (Nt-proBNP) and its value in the diagnosis of CTPH in patients with previous PE. Patients were evaluated with echocardiography at least 6 months after the index event. Pulmonary hypertension was defined as PAPs ≥40 mmHg at rest. Each subject underwent measurement of Nt-proBNP. Forty-nine patients were enrolled (mean age 64.5 ± 13.1 years; 22 men). Seven patients had CTPH, and two were symptomatic. There was a good correlation between PAP on echocardiography and Nt-proBNP (r 0.64; P = 0.00003). Nt-proBNP was elevated in 6 of 7 patients [sensitivity: 85.7%; 95% confidence interval (CI): 48.7, 97.4] and it was normal in 35 of 42 patients without CTPH (specificity: 76.2%; 95% CI: 61.5, 86.5%). Six of the 13 patients with high Nt-proBNP levels had CTPH, whereas 1 of 36 patients with normal Nt-proBNP levels had pulmonary hypertension. The resulting positive predictive value was 46.1% (95% CI: 19.2, 74.9), and the negative predictive value was 97.2% (95% CI: 85.5–99.9). In conclusion, Nt-proBNP correlates with PAPs and may be used to exclude preclinical or symptomatic CTPH in patients with previous PE. Prospective studies on a larger population are warranted to confirm our preliminary findings.     

Brachial-ankle pulse wave velocity as a marker of subclinical organ damage in middle-aged patients with hypertension

OBJECTIVE: This study was conducted to clarify whether the brachial-ankle pulse wave velocity (baPWV) might serve as a marker of target organ damage in middle-aged hypertensive subjects. METHODS AND RESULTS: Multivariate linear regression analysis demonstrated that while the baPWV showed a significant relationship to the intima-media thickness of the carotid artery (IMT), no such relationship was observed between the baPWV and the left ventricular mass index as assessed by echocardiography or the estimated glomerular filtration rate in either the 162 hypertensive patients who had never previously received antihypertensive medication or the 269 hypertensive patients who were under antihypertensive medication for at least 1 year. Receiver-operator characteristic (ROC) curve analysis suggested that a baPWV=18m/s was the best cutoff value to identify increased IMT in hypertensive patients who had never previously received antihypertensive medication (area under curve=0.77). Binary logistic regression analysis demonstrated that the odds ratio (OR) of a baPWV of >/=18m/s for identifying increased IMT {OR=7.38 (1.94-28.05)} was significant, even after adjustments. In hypertensive patients who had been under antihypertensive medication for at least 1 year, however, the area under the curve and OR were only modest. CONCLUSION: The baPWV may be a marker of carotid atherosclerosis, rather than of left ventricular hypertrophy or renal insufficiency, especially in middle-aged hypertensive subjects (subjects in their 30s to 60s), not only in those who have never previously received antihypertensive medication, but also in those who are under antihypertensive medication.     

慢性阻塞性肺疾病并发肺动脉高压血清标志物研究

目的探讨慢性阻塞性肺疾病(慢阻肺)患者血清中C反应蛋白(CRP)、内皮素-1(ET-1)、N端-前脑钠肽(NT-PROBNP)和血管内皮生长因子(VEGF)水平与肺动脉收缩压(PASP)之间的关系。方法研究对象来源于南京医科大学附属淮安一院呼吸内科2012年1月-2015年6月收治的286例慢阻肺急性加重期患者。按肺动脉收缩压升高程度分为轻度、中度和重度。采用ELISA试剂盒检测各血清学CRP、ET-1、NT-PROBNP和VEGF的水平。结果 CRP和ET-1在慢阻肺并发肺动脉高压(PAH)组患者均较单纯慢阻肺组升高(P0.05),慢阻肺并发轻、中度PAH时,CRP和ET-1水平升高与肺动脉压力呈显著正相关性(P0.05);慢阻肺并发轻、中和重度PAH时,NT-PROBNP水平较单纯慢阻肺组升高,并且与肺动脉压力呈显著正相关性(P0.05);慢阻肺并发肺动脉轻度和中度升高时,VEGF水平均较单纯慢阻肺组升高(P0.05),慢阻肺合并肺动脉重度升高时,VEGF水平反而较轻度和中度升高组明显降低(P0.05)。结论联合监测CRP、ET-1、NT-PROBNP和VEGF,对于预判慢阻肺患者肺动脉压力的升高及其程度,慢阻肺继发性PAH的早期诊断和预后判断有着重要的临床意义。     

原发性高血压患者肺静脉血流超声特征

目的 :测量原发性高血压 ( EH)患者肺静脉血流 ( PVF)特征 ,以重新评估左室舒张功能的变化。方法 :使用 HP- 5 5 0 0型彩色多普勒超声诊断仪 ,对 95例 EH患者 ( EH组 ) ,19例正常人 (对照组 )的右上 PVF和二尖瓣血流的频谱进行对照研究。结果 :EH组的心房收缩期逆向 PVF A波速率显著高于对照组〔( 3 7.3 8± 5 .69)cm/ s∶ ( 2 6.16± 3 .12 ) cm/ s,P <0 .0 0 1〕。在 E/ A比值和左室心肌重量指数正常的 EH组 ,A波速率也显著高于对照组〔( 3 8.77± 4 .4 4 ) cm / s,P <0 .0 0 1〕。结论 :测定 EH患者 PVF的 A波速率更能敏感评估左心室舒张功能     

Vascular cell adhesion molecule-1 as a biochemical marker of left ventricular mass in the patients with hypertension

Plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular adhesion molecule-1 (sVCAM-1), and E-selectin were measured in 80 outpatients with uncomplicated essential hypertension. Although the levels of E-selectin and sICAM-1 were similar between the patients with and without left ventricular (LV) hypertrophy, sVCAM-1 level was significantly elevated in the patients with LV hypertrophy (759.7 ± 154.6 ng/mL v 984.4 ± 240.6 ng/mL, P < .0001). The LV mass normalized to body surface area or height were significantly correlated with sVCAM-1 (r = 0.615, P < .0001 and r = 0.571, P < .0001, respectively). These results indicate that a soluble adhesion molecule is correlated with LV mass in uncomplicated essential hypertensive patients.     

Interleukin 18 as a marker of disease activity and severity in patients with juvenile idiopathic arthritis

OBJECTIVE: To verify the importance of interleukin 18 (IL-18) in the pathogenesis of juvenile idiopathic arthritis (JIA). We measured IL-18 levels in synovial fluid (SF) and serum, and determined their correlation with measures of disease activity and severity. METHODS: Fifty patients with JIA (13 systemic, 13 polyarticular, 24 oligoarticular) and 25 matched controls were analyzed. Cytokine levels (IL-1beta, IL-1Ra, IL-6, and IL-18) were quantified in serum and SF by ELISA, and disease activity measures were evaluated immediately after knee articular puncture. Radiological assessment was made according to the Steinbrocker method. Statistical analysis was performed by Spearman's rank-order correlation and Mann-Whitney rank test. RESULTS: All the analyzed cytokine levels (IL-1, IL-1Ra, IL-6, and IL-18) were higher in patients' sera than in controls. Remarkably, in patients with JIA, IL-18 SF levels did not differ from those of serum; they were positively correlated. The levels of IL-18 (SF and serum) were positively correlated with measures of disease activity: C-reactive protein, number of active joints, and radiological score, as well as with levels of IL-1, IL-1Ra, and IL-6. Moreover, IL-18 and IL-6 levels in SF and serum were much higher in patients with systemic disease compared to the other types of disease onset. In contrast, IL-1 and IL-1Ra were not different among JIA subtypes. CONCLUSION: Our results strongly suggest the participation of IL-18 in the pathophysiology of JIA. The positive correlation of this cytokine with several measures of articular inflammation and disease severity suggests that IL-18 could be a better target for the treatment of arthritis.     

Carotid intima-media thickness as a marker of cardiovascular risk in hypertensive patients with coronary artery disease

BACKGROUND: The aim of this study was to examine the significance of ultrasound-measured carotid intima-media thickness (CIMT) in high-risk patients with hypertension and coronary artery disease (CAD), as an independent prognostic factor in determining the risk of all-cause death or future cardiovascular events. METHODS: The study included 297 consecutive patients (mean age +/- SD, 57 +/- 9.4 years) with diagnosed hypertension and CAD, referred for coronary angiography. The mean of maximal CIMT in two arterial segments bilaterally was calculated. The primary endpoint was a patient's death from all causes. Death, stroke, or myocardial infarction comprised the secondary, composite endpoint. RESULTS: There was a follow-up of 1 to 79 (mean, 41) months. The predictors of death in a multivariate Cox proportional hazards model were the number of stenosed coronary arteries (P = .007) and CIMT (P = .001). The risk of the secondary, composite endpoint (death, stroke, or myocardial infarction) was determined by diabetes (P = .008) and CIMT (P = .010). Nearly 99% of patients with "low CIMT" (< or =1.13 mm) survived for 5 years, versus 78% with "high CIMT" >1.13 mm (log-rank test; P < .001). For the secondary, composite endpoint (death, stroke, or myocardial infarction), the event-free survival rate was 95% (low CIMT), versus 74% after 5 years (high CIMT) (P < .008). CONCLUSIONS: Intima-media thickness of the carotid arteries is a strong and independent predictor of death and serious cardiovascular events in hypertensive patients with CAD referred for coronary angiography.     

Blood pressure control in patients with hypertension: a community-based study

The objective of own study was to investigate the quality of hypertension management in a rural Chinese population. A prospective cross-sectional study was conducted in 922 hypertensive patients in a regional community in southern China. The average systolic (SBP) and diastolic blood pressure (DBP) was 167.8 +/- 22.5 mmHg and 94.3 +/- 14.2 mmHg respectively. A total of 823 patients (89.3%) patients had a SBP of greater than or equal to 140 mmHg, and 596 (64.6%) had a DBP of greater than or equal to 90 mmHg. Fully 568 patients (69.7%) were treated with one or two antihypertensive drugs, mostly with calcium channel blockers. In patients treated with antihypertensive drugs, the average SBP and DBP were 170.3 +/- 23.1 mmHg and 96.2 +/- 14.8 mmHg, respectively. Blood pressure was poorly controlled in these hypertensive patients. Further studies are required to identify the barriers to the effective management of uncontrolled hypertension in a rural setting.