In-vivo Platelet Activation and Anomalous Thrombospondin Levels in Severe Falciparum Malaria

To investigate in vivo platelet function in acute falciparum malaria plasma concentrations of β-thromboglobulin (β-TG), platelet factor 4 (PF4) and thrombospondin (TSP) were determined in 10 severely-ill Thai patients and 11 healthy volunteers. 8 patients recovered. At presentation, the platelet counts of the 10 patients were significantly lower (p < 0.025) than those of the controls, and a slight but significant increase (p < 0.05) in β-TG/PF4 ratios in the patients suggested low-grade platelet activation. Presentation plasma β-TG and PF4 concentrations did not differ from control values, probably due to the opposing effects of decreased circulating platelet mass and increased activation. By contrast, admission concentrations of TSP in the surviving patients were markedly lower (p < 0.001) than those of the controls; β-TG/PF4 ratios, but not TSP levels, returned to normal during treatment. Hepatic dysfunction and oliguric renal failure probably contributed to a sustained increase in plasma β - TG and TSP in the 2 fatally ill patients, but associated elevated PF4 levels indicated concomitant platelet activation. Our results support the suggestion that in vivo platelet activation, which appears to be rapidly controlled by treatment, occurs in patients with severe, non-fatal falciparum malaria. TSP production, apparently from non-platelet sources, was decreased and/or its consumption was increased in these patients, perhaps by factors such as cytoadherence of infected erythrocytes and consequent endothelial damage.     

In-vivo Platelet Activation and Anomalous Thrombospondin Levels in Severe Falciparum Malaria

To investigate in vivo platelet function in acute falciparum malaria plasma concentrations of β-thromboglobulin (β-TG), platelet factor 4 (PF4) and thrombospondin (TSP) were determined in 10 severely-ill Thai patients and 11 healthy volunteers. 8 patients recovered. At presentation, the platelet counts of the 10 patients were significantly lower (p < 0.025) than those of the controls, and a slight but significant increase (p < 0.05) in β-TG/PF4 ratios in the patients suggested low-grade platelet activation. Presentation plasma β-TG and PF4 concentrations did not differ from control values, probably due to the opposing effects of decreased circulating platelet mass and increased activation. By contrast, admission concentrations of TSP in the surviving patients were markedly lower (p < 0.001) than those of the controls; β-TG/PF4 ratios, but not TSP levels, returned to normal during treatment. Hepatic dysfunction and oliguric renal failure probably contributed to a sustained increase in plasma β - TG and TSP in the 2 fatally ill patients, but associated elevated PF4 levels indicated concomitant platelet activation. Our results support the suggestion that in vivo platelet activation, which appears to be rapidly controlled by treatment, occurs in patients with severe, non-fatal falciparum malaria. TSP production, apparently from non-platelet sources, was decreased and/or its consumption was increased in these patients, perhaps by factors such as cytoadherence of infected erythrocytes and consequent endothelial damage.     

Platelet factor 4 and β-thromboglobulin mRNAs in circulating microparticles of trauma patients as diagnostic markers for deep vein thrombosis

Deep vein thrombosis (DVT) is a common complication after trauma. The development of markers to predict DVT in trauma patients is needed, and circulating microparticles (MPs) and their contents are possible candidates. In this study, we aimed to identify platelet factor 4 (PF4) and β-thromboglobulin (β-TG) mRNAs in circulating MPs as potential markers for DVT diagnosis in trauma patients. Fifteen trauma patients diagnosed with DVT and fifteen matched patients without DVT were included in this study. Fifteen healthy volunteers also were included as controls. Circulating MPs were obtained from the plasma of all study subjects. Annexin V+?MPs and platelet-derived MPs (PMPs) were quantified using flow cytometry. PF4 and β-TG mRNAs in MPs were determined by qPCR, and the common logarithm of relative quantitation (RQ) was calculated using the comparative Ct method. Receiver-operating characteristic (ROC) curves were performed to analyze the diagnostic value of PF4 and β-TG mRNAs. No significant differences were found in Annexin V+?MPs and PMPs levels between trauma patients with and without DVT. However, both PF4 and β-TG mRNAs in MPs from the DVT group were significantly higher than the non-DVT group and healthy controls (P?=?0.014 for PF4, P?=?0.010 for β-TG). The ROC curve analysis showed that both the PF4 mRNA (area-under curve (AUC) 0.756, P?=?0.017) and the β-TG mRNA (AUC 0.751, P?=?0.019) had a positive predictive value for DVT. This finding indicates that the PF4 and β-TG mRNAs in MPs may be used as potential biomarkers for DVT diagnosis in trauma patients.

     

Plasma beta-thromboglobulin to platelet factor 4 ratios as indices of vascular complications in essential hypertension

The ratio of the plasma level of beta-thromboglobulin (beta-TG) to platelet factor 4 (PF-4) which is regarded as a most reliable indicator of platelet activation in vivo, was followed in 52 subjects at various stages of essential hypertension according to the WHO classification. These comprised 30 cases at stage I, 19 cases at stage II and three cases at stage III, and 20 age-matched normotensive control subjects. The observed beta-TG:PF-4 ratio in the hypertensive patients was 4.59 +/- 0.20, which was significantly higher than the value of 3.13 +/- 0.19 recorded in the normotensive control subjects. According to the WHO classification, beta-TG:PF-4 ratios in hypertensive patients at stages I, II and III were 3.93 +/- 0.19, 5.31 +/- 0.35 and 6.56 +/- 0.12, respectively. The beta-TG:PF-4 ratio revealed a tendency of platelet activation to increase with advanced progress of hypertensive vascular lesions. These results suggest that the abnormal platelet function observed in patients with essential hypertension plays an important role in the development of hypertensive vascular complications.     

Measurement of soluble C-type lectin-like receptor 2 in human plasma

Detection of platelet activation in vivo is useful to identify patients at risk of thrombotic diseases. Platelet factor 4 (PF4) and β-thromboglobulin (β-TG) are used for this purpose; however, they are easily released upon the minimal platelet activation that occurs during sampling. Soluble forms of several platelet membrane proteins are released upon platelet activation; however, the soluble form of C-type lectin-like receptor 2 (sCLEC-2) has not yet been fully investigated. Western blotting with an anti-CLEC-2 antibody showed that sCLEC-2 was released from washed human platelets stimulated with collagen mimetics. To detect sCLEC-2 in plasma, we established a sandwich enzyme-linked immunosorbent assay (ELISA) using F(ab′)2 anti-CLEC-2 monoclonal antibodies. Although plasma mixed with citrate, adenosine, theophylline and adenosine (CTAD) is needed for the PF4 and β-TG assays, effects of anti-coagulants (EDTA, citrate and CTAD) on the sCLEC-2 ELISA were negligible. Moreover, while special techniques are required for blood sampling and sample preparation for PF4 and β-TG assay, the standard blood collections procedures used in daily clinical laboratory tests have shown to suffice for sCLEC-2 analysis. In this study, we found that two forms of sCLEC-2 are released after platelet activation: a shed fragment and a microparticle-bound full-length protein, both of which are detected by the sCLEC-2 ELISA. The average concentration of sCLEC-2 in the plasma of 10 healthy individuals was 97?±?55?pg/ml, whereas that in the plasma of 25 patients with diabetes mellitus (DM) was 149?±?260?pg/ml. A trend towards an increase in sCLEC-2 concentration in the DM patients may reflect in vivo platelet activation in the patients, suggesting that sCLEC-2 may have clinical significance as a biomarker of in vivo platelet activation.     

Increased expression of plasma membrane Ca(2+)ATPase 4b in platelets from hypertensives: a new sign of abnormal thrombopoiesis?

Platelet Ca(2+) homeostasis is controlled by a multi-Ca(2+)ATPase system including two PMCA (plasma membrane Ca(2+)ATPase) and seven SERCA (sarco/endoplasmic reticulum Ca(2+)ATPase) isoforms. Previous studies have shown similar platelet Ca(2+) abnormalities in diabetic and hypertensive patients, including an increase in intracellular [Ca(2+)](I), a possible modulation of PMCA activity and increased PMCA tyrosine phosphorylation. Very recently, we found that platelets from diabetic patients also exhibited increased PMCA4b expression. In the present study we looked for further similarities between diabetic and hypertensive patients. We first confirmed a decrease in Ca(2+)ATPase activity (mean 55 + 7%) in mixed platelet membranes isolated from 10 patients with hypertension compared with those from 10 healthy controls. In addition, the decreased Ca(2+)ATPase activity correlated with the DBP of the different patients, as expected for PMCA activity. Second, we performed a pilot study of six hypertensives to examine their expressions of PMCA and SERCA mRNA and proteins. Like the diabetic patients, 100% of hypertensives were found to present a major increase in PMCA4b expression (mean value of 218 +/- 21%). We thus determined that platelets from diabetic and hypertensive patients showed similar increased PMCA4b isoform. Since increased PMCA4b expression was recently found to be associated with a perturbation of megakaryocytopoiesis, these findings may also point to an abnormality in platelet maturation in hypertension.     

In vivo platelet activation in mild arterial hypertension

In order to investigate whether an altered "in vivo" platelet serotonin release contributes to the low platelet serotonin content observed in essential hypertensive patients, we have measured plasma concentrations of beta-thromboglobulin and platelet factor 4, urinary beta-thromboglobulin concentrations and platelet serotonin and platelet factor 4 contents in 11 untreated essential hypertensive patients (WHO Stage I) and in 12 age-matched normotensive controls. Beta-thromboglobulin and platelet factor 4 are specific platelet proteins localized in the alpha-granules which are released during in vivo platelet activation. Plasma and urinary concentrations of these alpha granule proteins determined by radioimmunoassay were found to be similar in hypertensive and normotensive subjects. The low platelet serotonin content determined by high pressure liquid chromatography from platelet rich plasma in hypertensive patients (0.282 +/- 0.008 vs 0.348 +/- 0.019 nmol/10(8) platelets, p less than 0.01) was not associated with a decrease in platelet 4 content (1.36 +/- 0.07 vs 1.36 +/- 0.10 microgram/10(8) platelets). This study shows that platelet alpha-granule content is unaltered in uncomplicated essential hypertension and suggests that the low platelet serotonin content in hypertensives is mainly due to the inhibition of platelet serotonin uptake.     

The mean platelet volume in patients with essential and white coat hypertension

Mean platelet volume (MPV), a determinant of platelet function, is a newly emerging risk factor for atherothrombosis. The risk profile of white coat hypertension has not yet been completely clear. The present study was designed to evaluate MPV in white coat hypertensive subjects compared with essential hypertensive patients and normotensive subjects. We selected 36 essential hypertensive patients, 36 white coat hypertensive subjects and 36 normotensive control subjects matched for age, gender, and body mass index. MPV was very significantly higher in essential hypertensives and white coat hypertensives than in normotensives (P < 0.00); it was also higher in essential hypertensives than in white coat hypertensives (P < 0.05). Platelet counts were not different among the study groups (P > 0.05). MPV was positively correlated with ambulatory diastolic blood pressure in essential hypertension and white coat hypertension groups (P < 0.05). In conclusion, our data suggests one possible mechanism by which white coat hypertensive subjects may be at increased cardiovascular risk.     

Evaluation of regional haemodynamics and alterations of vascular wall of the lower limbs in hypertensive subjects

This study was designed to analyse the relationship betweenarterial hypertension and changes in arterial blood flow andvascular wall damage of the lower limbs in hypertensive patientswith various degrees of hypertension. Six hundred and fifty-four hypertensive patients (421 malesand 233 females) aged 35 to 70 years and 88 healthy subjects(63 males and 25 females) aged 39 to 60 years were studied.Strain-gauge plethysmography of the lower limbs was used tocalculate arterial calf blood flow (RF), arterial calf bloodflow after post-ischaemic hyperaemia (PF), basal and minimalvascular resistances (BVR and MVR), time to reach peak flow(tPF), time until 50% reduction of peak flow (tT) and totalrecovery time (tT). In 108 (67 males and 41 females) of the hypertensive patients,a morphological study by echo-Doppler duplex scanning of thepopliteal artery was performed to measure medial-intimal thickeningand popliteal lumen diameter. Our results indicate that regional haemodynamics of the lowerlimbs worsened in hypertensives in comparison with control subjects.In addition, the change in peripheral haemodynamics was relatedto the degree of hypertension. Moreover, medial-intimal thickeningwas significantly (P<0.05) higher in severe hypertensivesthan mild hypertensives. Popliteal lumen diameter was significantly(P<0.05) lower in severe hypertensives than moderate andmild hypertensives. In all these subjects mean blood pressurewas correlated directly (r=0.31; P<0.001) with medial-intimalthickening and inversely (r= – 0.37; P<0.001) withpopliteal lumen diameter. Multiple regression analysis indicatedthat mean blood pressure, age and serum cholesterol were independentlycorrelated to medial-intimal thickening. This relationship wasnot influenced by the diabetic patients and smokers among thegroups. Our results indicate that hypertension impairs peripheral flowand encourages the development of medial-intimal thickening.     

Plasma and cellular factors of atherogenesis and the prostanoid system at the early stages of arterial hypertension

In young patients with borderline arterial hypertension and, to a greater extent, with Stage 1 hypertensive disease (HD), changes were found in the proatherogenic plasma lipid and apoprotein composition, which were manifested as higher levels of total cholesterol, triglycerides, low and very low density lipoprotein cholesterols along with increased apolipoprotein B and apolipoprotein B:apolipoprotein AI ratio. The prostacyclin-thromboxane system in borderline arterial hypertension was in an activated state by retaining the physiological ratio of its components. The patients with Stage I HD exhibited a considerable increase in thromboxane activity, which determined the system's imbalance towards its predominance. In Stage I HD, the thrombocytic link of hemostasis was characterized by enhanced platelet aggregability mediated by the imbalance of the prostacyclin-thromboxane system in the direction of thromboxane.     

Repeated office blood pressure controls reduce the prevalence of white-coat hypertension and detect a group of white-coat normotensive patients

BACKGROUND: The aim of this study was to evaluate whether repeated office blood pressure controls may change the prevalence of white-coat hypertension among hypertensive patients. METHODS: We studied 221 newly diagnosed, never-treated hypertensive patients, all men, aged 31-60 years. On the first visit, they underwent sitting blood pressure measurements (two readings were taken by mercury sphygmomanometer and averaged) and non-invasive 24 h ambulatory blood pressure monitoring (ABPM) every 15 min. Thereafter, each patient made four further visits over an 8-week period. On each visit, three sitting readings were taken and averaged. On the last visit, ABPM was performed again. Subjects who had hypertension in the clinic but whose daytime ambulatory blood pressure was less than 134/90 mmHg were considered to have white-coat hypertension. RESULTS: On the first visit, all patients were, by definition, clinically hypertensive and ABPM detected a prevalence of white-coat hypertension of 25.8%. On the following visits, the prevalence of clinical hypertensive patients progressively declined; on the last visit, the 82.3% of all patients resulted yet clinical hypertensive: on ambulatory blood pressure 71.9% were sustained hypertensives, whereas 10.4 had white-coat hypertension. Of the patients originally labelled as hypertensive, 17.7% proved to be clinically normotensive: 13.6% had also daytime ambulatory blood pressure in the normal range, whereas 4.1% showed elevated blood pressure during daytime ABPM (white-coat normotensives). CONCLUSION: These data suggest that repeated office blood pressure controls in newly diagnosed hypertensives reduce the number of office hypertensive patients, reduce the number of white-coat hypertensive patients and detect a small group of white-coat normotensive patients.     

A prospective study of haemostatic parameters in relation to the clinical course of myeloproliferative disorders

Abstract: Platelet function and the clinical course of the disease were prospectively investigated in 29 patients with myeloproliferative disorders. Serial determinations (median: 5 investigations per patient within 17 months) of platelet aggregation, plasma and intraplatelet concentrations of β-thromboglobulin (βTG) and platelet factor 4 (PF4), and of fibrino-peptide A (FPA) plasma levels were carried out. In the chronic phase of polycythaemia vera, patients with thrombohaemorrhagic complications during the study period had higher platelet count, more severe platelet aggregation defects, and increased plasma levels of βTG and FPA compared to patients without complications. However, thrombohaemorrhagic complications were not predicted by changes in these parameters in the individual patient during the chronic disease phase. When patients with chronic myelogenous leukaemia entered blast crisis, bleeding complications were related to thrombocytopenia, impaired platelet function and low intraplatelet concentrations of βTG and PF4. Cytoreduction by chemotherapy in the chronic phase of CML did not alter βTG and PF4 plasma levels, whereas treatment of polycythaemia rubra vera by venesection favourably influenced platelet α-granule secretion and increased intraplatelet concentrations of βTG and PF4.     

Acute Effects of Cigarette Smoking on Platelet Function and Plasma Catecholamines in Hypertensive and Normotensive Men

In this randomized controlled crossover study essential hypertensive men (n = 13) and matched normotensive controls (n = 18) were examined before and during cigarette and sham smoking to assess the acute effects of smoking on platelets and plasma catecholamines. Platelet activity in vivo was determined by measurements of the released α-granule constituent β-thromboglobulin (β-TG) in plasma and in urine. Urinary high molecular weight β-TG and venous plasma epinephrine increased significantly during smoking in the hypertensive group, but not among the normotensive men. Thus, cigarette smoking induces a mild platelet release reaction and also elicits a significantly higher epinephrine response in hypertensive men compared to normotensive controls.     

白大衣高血压患者的血小板功能

目的:探讨白大衣高血压(WCH)患者的血小板功能.方法:选初诊的原发性高血压(EH)患者、 WCH 患者、正常血压(NT)者各35例,通过诊室血压测量和24 h动态血压监测,同时测定并比较3组血小板最大聚集率(PAGTmax)、血浆血小板α-颗粒膜蛋白(GMP-140)含量、平均血小板容积(MPV) 、血小板数量的变化.结果:和NT对照组相比,EH组和WCH组 PAGTmax、血浆血小板GMP-140含量、MPV均明显增加(P<0.05)而三组血小板计数无统计学差异,同时EH组的PAGTmax、血浆血小板GMP-140含量、MPV均高于WCH组(P<0.05).EH组和WCH组MPV与24 h平均舒张压、GMP-140含量均正相关( P<0.05).结论:WCH存在血小板活化,可能和心血管事件发生率增加有关.     

A pilot assessment of oxidative stress byproducts and antioxidant activities among Indian patients with various stages of hypertension

In humans, hypertension is considered a state of oxidative stress that can contribute to the development of atherosclerosis and other hypertension-induced organ damages. The objective of this study was to evaluate oxidative status, antioxidant activities, and oxidative stress by-products among Indian patients with various stages of hypertension. Lipid profile, enzymatic and non-enzymatic antioxidants, lipid peroxidation as thiobarbituric acid reactive substances (TBARS), C-reactive protein, electrolytes, and minerals were analyzed in the blood of newly diagnosed prehypertensives, stage I and II hypertensives (n = 20 in each group) and were compared to their age-matched normotensives. Elevated levels of lipid profile (except high density lipoprotein cholesterol [HDL-C]) were observed in stage I and II hypertensive patients. Enzymatic and non-enzymatic antioxidants were significantly (P < 0.05) lower, while TBARS and C-reactive protein were higher in prehypertensives, and stage I and II hypertensives. Significant (P <0.05) changes were also observed in the plasma Na(+) and K(+) concentrations among the hypertensive groups. Serum levels of zinc, copper, and magnesium were significantly (P < 0.05) lower in prehypertensives, and stage I and II hypertensives as compared to normotensives. The study indicated a strong association between blood pressure (BP) and oxidative stress-related parameters and suggests a possible role of oxidative stress in the development of elevated BP.     

A study of lipid levels in uncomplicated hypertension

A number of risk factors for coronary artery disease are known to be present in hypertensive patients, the most important being hyperlipidemia. An analysis of the lipid profiles of 3,182 uncomplicated non-diabetic patients (2,425 males, 757 females) who attended two institutions of Patna city between 1992-1998 was conducted alongwith 4,131 controls. Mean total cholesterol was slightly higher (but statistically significant; p < or = 0.05) in hypertensives (191.8 mg/dL vs 190.1 mg/dL) as compared to the control group; mean total cholesterol-HDL ratio was also higher (4.65 vs 4.48) in hypertensives (p < or = 0.05). As per National Cholesterol Education Programme guidelines, 1,069 (33.6%) patients had cholesterol level above 200 mg/dL while 850 (26.7%) had triglycerides over 200 mg/dL among the hypertensive group. An abnormal total cholesterol-HDL ratio (> 4.5) was found in 1,600 (50.3%) of the hypertensives; this was by far the most common abnormality. With increasing severity of hypertension, the prevalence of elevated total cholesterol, LDL cholesterol and low HDL cholesterol was higher; triglyceride levels were less affected. These results indicate that an abnormal total cholesterol-HDL ratio is the most common variety of dyslipidemia in uncomplicated hypertension.     

Mean platelet volume and β-thromboglobulin levels in familial mediterranean fever: Effect of colchicine use?

BackgroundMany studies have shown that subclinical inflammation persisted during remission period of Familial Mediterranean Fever (FMF) patients but long term effects of subclinical inflammation in these patients aren't clearly known. Besides, a few of the recent studies revealed that risk of atherosclerosis had increased in FMF patients. β-Thromboglobulin (β-TG) is considered as a sensitive marker of platelet activation. In this study Mean Platelet Volume (MPV) and β-TG levels were evaluated in FMF patients.MethodsFollowing the Local Ethics Committee's consent, 25 FMF patients were included in the study. Twenty eight age and sex matched healthy volunteers were recruited as a control group. Lipid profile, inflammatory parameters, hemogram, β-TG, MPV were assessed. Statistical analysis was performed with SPSS for Windows 16.00.ResultsGroup I consisted of 25 FMF cases (16 females, 9 males; mean age: 35.72 ± 12.34 years), Group II consisted of 28 cases (22 females, 6 males; mean age 31.78 ± 10.31 years). There was no statistically significant difference between the groups in terms of age and gender distribution, smoking status, total cholesterol, triglyceride, LDL and MPV (p > 0.05). HDL levels were found to be statistically lower in Group I (p:0.04). Median β-TG levels was significantly higher in Group II than Group I (129.50 (range:372.00) ng/mL versus 104.00 (range:212.80) ng/mL respectively; p:0.03).ConclusionIn this study MPV and β-TG were evaluated for FMF cases and healthy controls, β-TG levels were found significantly lower among patients; we hypothesized that this difference may have resulted from the effect of colchicine use on platelet functions.     

Hyperinsulinemia,family history of hypertension,and essential hypertension

The aim of this study was the evaluation of the relationships among hyperinsulinemia, a family history of hypertension, and essential hypertension. Insulin and C-peptide responses to an oral glucose load were studied in 175 lean normotensives (N) and untreated hypertensives (H) with (F+) and without (F−) a family history of hypertension: 30 NF-, 30 NF+, 45 HF-, and 70 HF+. The groups were comparable for age, sex, body mass index, and blood pressure. The following parameters were evaluated: plasma glucose (G), serum insulin (I), and C-peptide (Cp) before and 30, 60, 90, and 120 min after the glucose load, fasting glucose/insulin ratio (ISI), fasting insulin/C-peptide ratio (I/Cp), and 24-h ambulatory blood pressure monitoring. Plasma glucose was measured, fasting and during the test, and it and I/Cp were similar in the four groups. Serum insulin and Cp, both fasting and stimulated, were significantly higher and ISI lower in normotensives and hypertensives with hypertensive parents. Grouping the subjects first on the basis of blood pressure and then on the basis of family history, no differences were found between normotensives and hypertensives, whereas I and Cp, fasting and stimulated, were significantly higher and ISI lower in subjects with positive as compared to negative family history. The closest correlations between insulin and ambulatory blood pressure were found in normotensives with hypertensive parents; in hypertensives with hypertensive parents we only found a direct correlation between fasting Cp and nocturnal blood pressure fall; in hypertensives with normotensive parents insulin inversely correlated with nocturnal blood pressure fall. Insulin resistance seems to have a familial basis, independently of the presence of hypertension. Instead of showing a causal relationship between insulin resistance and hypertension, our results indicate that the two are partly independent components of a common familial pattern.     

Gene polymorphisms of the renin-angiotensin system and early development of hypertension

BACKGROUND: A case-control association study was conducted to investigate a possible involvement of polymorphisms of three renin-angiotensin system genes: ACE (I/D and T-3892C), AGT (M235T and T174M), and AT1R (A1166C) in the early development of hypertension. METHODS: One hundred nineteen hypertensive and 125 normotensive participants aged 18 to 40 years were selected from a broader sample representative of the general population of Croatia. The selection criteria for hypertensive cases were systolic blood pressure (BP) higher than 140 mm Hg or diastolic BP higher than 90 mm Hg and a history of hypertension according to patient interview. RESULTS: Among the polymorphisms investigated, only those located on the ACE gene were associated with hypertension. For ACE I/D, the odds ratio for hypertension of DD versus II homozygote individuals was 2.50 (95% confidence interval [CI] 1.19-5.25) and for ACE T-3892C, the odds ratio of CC versus TT individuals was 2.32 (95% CI 1.05-5.10). Both polymorphisms of the ACE gene were in tight linkage disequilibrium. Of the investigated risk factors for hypertension, only body mass index (BMI) showed an influence on the early development of hypertension, acting independently of the ACE polymorphism. Their additive effect gives rise to 86% of hypertensives in subjects having both the DD genotype and BMI >or=30 kg/m(2). CONCLUSIONS: The present study provides evidence of the association of the ACE gene polymorphisms and premature hypertension. In addition, BMI proved to be another important predictor of the disorder acting independently of the ACE gene.     

Evaluation of effect of smoking and hypertension on serum lipid profile and oxidative stress

ObjectiveTo determine the effect of smoking, hypertension individually on lipid profile and lipid peroxidation and the cumulative influence of smoking and hypertension on oxidative stress and lipid profile.MethodsSerum total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL), triglycerides and malondialdehyde (MDA) were estimated in sixty cases including twenty smokers, twenty hypertensives, and twenty smokers with hypertension and compared with those in twenty age and sex matched healthy controls.ResultsStatistically significant increase in MDA, total cholesterol, LDL, VLDL and triglycerides and decrease in HDL in cases were observed in smokers, hypertensives and smokers with hypertension when compared to healthy controls. Smokers had significantly elevated levels of lipid profile and MDA except for HDL when compared to hypertensive group. Statistically significant increase in the levels of study parameters of smoking and hypertensive group was noticed when compared to group with hypertensives (P<0.05) and there was a statistically significant decrease in HDL levels in smoking and hypertensive group when compared to healthy controls. All the biochemical study parameters had larger effects (0.80<d<1.20) for the smoking and hypertensive group in comparison with control group.ConclusionsCigarette smoking, together with hypertension, has larger effect on lipid profile than in patients with cigarette smoking or hypertension alone and induces alteration in serum lipid levels and oxidative stress in the direction of increased risk for coronary artery disease.