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The adipokine leptin is expressed at higher concentrations in obese subjects, who also incidentally have a higher prevalence of hypertension. The pathogenesis of this obesity-related hypertension is controversial and is believed to be related to many factors including increased sympathetic activity, abnormalities of the renin-angiotensin system, sodium retention, and an endotheliopathy acting independently or in concert with increased circulating leptin. This review discusses the potential mechanisms through which changes in leptin signal transduction pathways in tissues with the leptin receptor, especially the hypothalamus, mediate the pathogenetic relationships between obesity and hypertension. The hypothesis is explored that leptin effects on blood pressure (BP) are meditated by the downstream effects of hypothalamic leptin signaling and ultimately result in activation of specific melanocortin receptors located on sympathetic neurons in the spinal cord. The physiological consequences of this sympathetic activation of the heart and kidney are activation of the renin-angiotensin system, sodium retention and circulatory expansion and finally, elevated BP. This sequence of events has been elegantly demonstrated with leptin infusion and gene knockout studies in animal models but has not been convincingly reproducibly confirmed in humans. Further studies in human subjects on the specific roles of hypothalamic leptin in essential hypertension are indicated as elucidation of the signaling pathways should provide better understanding of the role of weight loss in BP control and afford an additional mechanism for pharmacologic control of BP in adults and children at risk of cardiovascular disease.

Introduction: Immunological, genetic and environmental factors are believed to play important roles in the pathogenesis of Multiple Sclerosis (MS). There have been many studies on risk factors for MS but these have been mainly in Caucasian populations; robust studies in Arab populations remain relatively uncommon. This study therefore aimed to identify behavioral, socio-cultural, and demographic factors associated with development of MS in Kuwait, a high income Arab country, currently undergoing a demographic transition., Subjects and Methods: In this case- control study, 195 Kuwaiti MS patients and 146 healthy age and sex-matched controls were recruited. Both groups of subjects were interviewed using a structured questionnaire, in relation to anthropometric, socio-cultural and demographic data, residence during the 1990/91 Gulf War and current and past medical history, including medications. We also clinically evaluated, and retrospectively reviewed medical records of patients to derive appropriate clinical information, including associated chronic medical illness requiring long-term treatment., Results: On multiple logistic regression analysis after adjustment for potential confounders including age, gender and BMI, in all the subjects, a positive associations prevail with presence of MS and some sociocultural and demographic factors, which included non-Bedouin ethnicity (AOR 2, 95% CI 1.0-3.9, p 0.049), positive family history of MS (AOR 10.6, 95% CI 3.0-36.9), p < 0.001), and low daily sunlight exposure of < 15min/day (AOR 5.3, 95% CI 2.7-10.5 p < 0.001). In addition, while 41.8% of MS patients indicated at least one comorbidity, only 26.8% of the controls reported any associated physical illness, with the suggestion that presence of certain comorbidities might increase MS risk (AOR 2.4, 95% CI 1.3-4.7, p < 0.001). Other risk variables such as smoking status and mode of routine outdoor dressing were not significant in all the MS subjects taken as a whole, but demonstrated variably positive associations in the MS subgroup classified as those with established disease and those who were newly diagnosed and drug naïve., Conclusions: This study suggests that a positive family history of MS and presence of certain comorbidities appeared to be associated with an increased risk of developing MS. In contrast, relatively increased amount of daily sunlight exposure and Bedouin ethnicity appear to somewhat be protective. It is speculated that the relationship of sunlight exposure with MS might be due to vitamin D availability, and is deserving of further study.

The metabolic syndrome is a combination of metabolic and clinical features that aggregate in individuals and increase cardiovascular disease (CVD) risk considerably. It is believed, although sometimes controversially, that the underlying basis for this syndrome is insulin resistance (IR) and accompanying compensatory hyperinsulinemia. Insulin and insulin-like growth factors (IGFs) have significant homology and interact with differing affinity with the same receptors. Therefore, their actions can be complementary, and this becomes particularly significant clinico-pathologically when their circulating levels are altered. This review of currently available information attempts to answer the following questions: (1) Is there any evidence for changes in the components of the IGF system in individuals with established CVD or with increased CVD risk as with the metabolic syndrome? (2) What are the underlying mechanisms for interactions, if any, between insulin and the IGF system, in the genesis of CVD? (3) Can knowledge of the pathophysiological changes in the IGF system observed in macrosomic newborn infants and growth hormone (GH)-treated children and adults explain some of the observations in relation to the IGF system and the metabolic syndrome? (4) Can the experimental and clinical evidence adduced from the foregoing be useful in designing novel therapies for the prevention, treatment, and assignment of prognosis in metabolic syndrome-associated disease, particularly ischemic heart disease? To answer these questions, we have performed a literature review using bibliographies from PubMed, Medline, and Google Scholar published within the last 10 years. We suggest that IGF-1 levels are reduced consistently in individuals with the metabolic syndrome and its components and in those with ischemic CVD. Such changes are also seen with GH deficiency in which these changes are partially reversible with GH treatment. Furthermore, changes are seen in levels and interactions of IGF-binding proteins in these disorders, and some of these changes appear to be independent of IGF-binding capability and could potentially impact on risk for the metabolic syndrome and CVD. The promising therapeutic implications of these observations are also discussed.

Objectives: The objective of this study was to explore the relationships between circulating uric acid and lipid levels and components of the metabolic syndrome (MetS) in Arab dyslipidemic patients, a group already at high coronary artery disease risk., Subjects and Methods: The medical records of 1,229 subjects (632 men, 597 women) referred for treatment of dyslipidemia and followed up for at least 12 months were reviewed. Serum levels of uric acid and lipids (total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein) and other variables in the National Cholesterol Education Program ATP III criteria definition of MetS were assessed at initial presentation and every 4- 6 months, under specific lipid-lowering treatment (statins and/or fibrates), in each of the subjects. Their respective associations were explored by appropriate logistic regression techniques with control for confounding risk factors, including age, gender and body mass index., Results: 306 subjects (24.9%) of the study population were hyperuricemic; they were more likely to be men, obese and diabetic. Also the serum uric acid level (mean ± SD) was greater in men with MetS compared with men without (377.0 ± 98.0 vs. 361.6 ± 83.1 μmol/l, p < 0.05), an observation not reproduced in women. Uric acid levels had significant associations with the presence of fasting hyperglycemia, hypertension and large waist circumference (WC) in men, but only with large WC in women. With statin treatment, uric acid levels decreased by 10% within 1 year of treatment; with fibrates, uric acid levels remained unchanged or slightly increased., Conclusion: The data showed that hyperuricemia is common in dyslipidemic patients in Kuwait, where its important determinants are male sex, obesity, diabetes and statin treatment., (Copyright © 2011 S. Karger AG, Basel.)

Background: Acute coronary syndromes present clinically as a consequence of plaque rupture and thrombosis possibly related to altered homeostasis of thrombogenic factors. It is speculated that this vulnerability in adults should be predictable from blood levels of thrombogenic biomarkers in children and adolescents. This study aims to examine the determinants and blood levels of lipoprotein(a) [Lp(a)], fibrinogen (FBG) and plasminogen activator inhibitor-1 (PAI-1) in healthy adolescents stratified according to age group, gender and body mass., Methods: A total of 774 (316 males 458 females) healthy adolescent Arab subjects aged 10-19 years and attending secondary schools in Kuwait were interviewed by a validated questionnaire for variables relating to socio-demographic variables, diet and physical activity. They also had anthropometry, BP measurement and determination of fasting blood levels of Lp(a), low density lipoprotein (LDL)-cholesterol, apolipoprotein (apo) B, PAI-1 activity and FBG., Results: The median (interquartile range, IQR) plasma levels of PAI-1 activity, FBG, Lp(a) and apoB were respectively 1.59 (0.58-3.78) U/mL, 296 (190-417) mg/dL, 10.0 (4.8-21.0) mg/dL and 0.72 (0.60-0.85) g/L. Boys had significantly higher PAI-1, FBG and apoB concentrations than the girls, although Lp(a) levels were greater in the latter. The overweight and obese subjects tended to have higher levels of LDL, apoB, FBG and PAI-1 but not Lp(a). Furthermore, the younger adolescent males and females (age <14 years) consistently had higher FBG levels than the older ones (age >14 years). Lp(a) and PAI-1 levels did not appear significantly influenced by this age stratification. Bivariate and multivariate analyses with adjustment for putative body mass index (BMI) confounders indicated that the independent determinants of these biomarkers were (i) Lp(a): apoB, gender; (ii) PAI-1: BMI, apoB, diet; (iii) FBG: BMI, gender, age, family income; and (iv) apoB: BMI, gender and PAI-1., Conclusions: The blood levels of the prothrombotic biomarkers ;ibLp(a), PAI-1, and FBG;ic in healthy Kuwaiti adolescent subjects are variably influenced by age, gender, body mass and socio-demographic factors.

The concept of metabolic syndrome in psychiatry provides a united front for confronting a series of metabolic changes that are predictive of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM), which are highly prevalent in severe mental disorders (SMDs), such as schizophrenia, bipolar disorders, and severe depression. This review attempts to answer the following questions: (1) Is there evidence of significantly increased risk of metabolic syndrome in SMDs? (2) How is this evidence explained by stress theory and functional polymorphism? (3) What role can psychopharmacology and psychosocial therapies play in minimizing the problem? We have done a historical review using related literature from Medline. Compared with the general population, metabolic syndrome is two to three times more common in SMDs. The evidence for this predates the era of antipsychotic drugs. Altered glucose metabolism and dyslipidemia seem to be integral to SMDs. However, major psychotropic drugs are associated with metabolic syndrome, because of their activity at the appetite-stimulating receptors. SMDs seem to trigger a pathogenic cycle that fuels metabolic syndrome. To explain these findings, a neural diathesis-stress model has been proposed. Furthermore, candidate genes associated with receptors for weight gain are implicated. Using metformin (≥750 mg/day) may significantly reduce metabolic risks, and the data support consideration of this intervention for psychiatric patients taking antipsychotics. The obstacles to the implementation of the available guidelines for monitoring metabolic effects and changing unhelpful lifestyles need to be overcome by making monitoring mandatory and integration of physical exercise into routine care. Drug development and genotyping for the risk factors are future solutions.

Background: A primipara with multiple pregnancy who booked for antenatal care at 21 weeks presented with vaginal bleeding and pedal oedema at the 27th week. She had had five previous ultrasound scans that gave conflicting results., Materials and Methods: The patient was therefore sent for a confirmatory scan, which was performed using a linear 3.5 MHz transducer of a dynamic imaging dedicated, concept MC ultrasound scan machine., Results: A diagnosis of conjoint twins was made. The twin was joined from the mandible to the abdomen. Although they cried at birth, they died a few minutes after. The pregnancy was terminated by caesarian section at the patient's request. The patient did well postpartum and was discharged on the 5th postoperative day. Records confirm that this is the first case seen in this hospital, which has been in existence for 18 years., Conclusion: To diagnose conjoint twins by ultrasound, one needs the expertise and careful scanning techniques, as the diagnosis may be easily missed, especially if the union is extensive.

Introduction: Important biochemical markers for the low-grade vascular inflammation and endothelial dysfunction that characterize the earliest events in the pathogenesis of atherosclerosis are CRP and the adhesion molecules ICAM-1 and VCAM-1. This study aims to evaluate, in healthy Arab adolescent subjects aged 10-19 yr, the reference ranges for these markers and their associations with such determinants as age, gender, body mass and insulin sensitivity., Methods: There were 774 Kuwaiti subjects (316 boys and 456 girls) aged mean (SD) 14.5 (2.2) yr. All had detailed clinical examination, anthropometry (to derive BMI) and assessment of fasting serum levels of CRP, ICAM-1, VCAM-1 and insulin (and HOMA-IR) to derive their reference values. Associations with putative determinants were explored by logistic regression analyses., Results and Discussion: The reference ranges (mean (SD)) were: CRP 0.28 (0.49) mg/dl; ICAM-1, 286 (119)ng/ml; VCAM-1, 1148 (352)ng/ml; HOMA-IR, 4.57 (5.05). These parameters were significantly higher in boys than in girls, and in the overweight/obese and those aged < or =14 yr. BMI was significantly and independently related to CRP and ICAM-1 even after adjusting for age, gender, socio-demographic factors, diet and exercise. Levels of these markers were significantly influenced by age and gender., Conclusion: BMI, age and gender are significant predictors of serum levels of circulating inflammatory biomarkers, particularly ICAM-1, CRP and HOMA-IR. These atherogenic processes therefore probably cluster together in early life in individuals at increased later heart disease risk. Preventive public health measures should therefore commence in early childhood., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

Introduction: The plasma B-type natriuretic peptide (BNP) level is elevated in cardiac ischemia and may be useful in assessing prognosis in acute coronary syndromes (ACS). This study aimed to: (1) establish BNP levels and its determinants in a healthy Gulf Arab population and in a group of patients with acute myocardial infarction and (2) investigate associations between BNP levels and markers of myocardial damage (ejection fractions, cardiac troponin I [cTnI] levels) and inflammation (serum C-reactive protein [CRP])., Subjects and Methods: We studied 2 groups of Arab subjects: (1) Healthy control (HC), 142 healthy control subjects; (2) Coronary heart disease (CHD), 257 patients with proven acute myocardial infarction within 1 day of admission. Each subject was assessed clinically, and ejection fractions (left ventricular ejection fraction [LVEF]) were determined by echocardiography in those with CHD. Fasting blood samples were processed for full blood counts and serum glucose, urea, creatinine, uric acid, and lipids (total cholesterol [TC], triglycerides [TG], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein [LDL], and apolipoprotein B [apoB]), cTnI, BNP, and high-sensitivity (hs) CRP levels. The results were compared between groups, and the associations of BNP with other parameters were explored., Results: In comparison to HC, the CHD group had a greater waist-hip ratio (WHR) (P < 0.01), worse atherogenic profile, worse renal function, and higher values for CRP and BNP (all P < 0.001). There were no significant differences in values for BNP related to age, diabetes, hypertension, WHR, and hematocrit, although there was a consistent trend in both HC and CHD groups toward a negative relationship of BNP with body mass, TG, and apoB levels, and a positive relationship with HDL, independent only for HDL and apoB on multiple logistic regression. No correlations could be established with cTnI, CRP, and LVEF. The patterns of cross-correlations did not differ significantly with diabetic status., Conclusion: In an Arab population with CHD, blood levels of BNP are higher than in a healthy control population and appear correlated to body mass and atherogenic lipids but not CRP, troponin, or ejection fraction. BNP levels did not appear to be influenced by the classical CHD risk factors of diabetes, hypertension, cigarette smoking, hematocrit, or WHR. The independent link with atherogenic dyslipidemia suggests that BNP is important in atherogenesis and may not be just an index of cardiac contractile dysfunction.

Schizophrenia may be associated with inflammatory reactions and C-reactive protein (CRP) is a nonspecific serum protein marker for persisting inflammatory states. This study aimed to assess concentrations of high sensitivity CRP (hsCRP) in schizophrenic Arab patients and evaluate the relationships of hsCRP levels with aspects of clinical phenotypes of the disease. Two age-matched groups of subjects were studied: (1) healthy controls, HC, n=165; (2) patients with schizophrenia, SZ: n=207. Each subject was evaluated with a standard questionnaire for age at disease onset, family history, disease severity and outcome. Serum hsCRP levels were measured by immunoassay. The two groups of subjects were similar in age, ethnic composition and socioeconomic status. Those with SZ had significantly greater serum concentrations of hsCRP. There were significant associations between hsCRP and (i) age in both groups; (ii) body mass index (BMI) in HC but not in SZ. In the latter, hsCRP levels were: (a) marginally higher in women with later age of disease onset; (ii) highest with remission and with catatonic features; and (iii) lower with family history of psychosis. The study concludes that serum levels of hsCRP are increased in clinically stable Arab patients with schizophrenia and appear related to the disorder's clinical expression. It is suggested that there may be an inflammatory component to schizophrenia which is associated with aspects of its clinical phenotype.

Background: Apolipoprotein E (APOE) is polymorphic, and may be involved in the pathogenesis and clinical expression of schizophrenia. This study aimed to investigate the frequency of specific APOE genotypes and alleles in a schizophrenic Arab population and evaluate the association of specific APOE types with clinical phenotypes of the disease., Subjects and Methods: Two age-matched groups of subjects were studied: (1) healthy controls, n = 165; (2) patients with schizophrenia (SZ), n = 207. Each subject was evaluated for age and mode of onset of disease, family history of psychosis, disease severity and outcome over the years of illness. APOE genotyping was performed by a validated PCR-RFLP technique., Results and Discussion: Genotype E3E2 and allele E2 were less frequent in the patients with schizophrenia (p = 0.04), and both APOE types tended to be more common in male than female schizophrenic patients (p = 0.08). Schizophrenic patients with a positive family history of psychosis had lower frequencies of genotype E3E2 and allele E2 (both p = 0.04). Genotype E3E4 and allele E4 were least common in patients with an age at onset of disease >31 years (OR: 5.5, 95% CI: 1.1-27.4), particularly in males., Conclusion: APOE genetic polymorphism potentially influences susceptibility to schizophrenia and may be associated with aspects of its phenotypic expression, particularly gender, age of onset and family history of psychotic illness. This relationship of APOE with schizophrenia is likely to be race- and gender-specific., (2009 S. Karger AG, Basel)

There is evidence of an association between hypothyroidism and coronary heart disease. We decided to look at the relationship between hypothyroidism and LDL subclasses' pattern including small, dense LDL to define a biochemical basis for better management of the CHD risk of these patients. We utilized a case-control design to evaluate differences in lipid parameters between cases and controls. Univariate analysis revealed that many factors were associated with LDL particle size. Binary logistic regression however revealed that only thyroid status and serum triglyceride (TG) levels were independently associated with LDL particle size. Results from this study support an independent association between LDL particle size phenotype and both plasma TG concentrations and thyroid status. After adjusting for TG levels, other insulin resistance syndrome (IRS) traits were not associated with LDL size phenotype, suggesting that the IRS related sdLDL is linked most strongly to alterations in TG levels.

One of the important risk factors for coronary heart disease is dyslipidemia. Several lipid abnormalities have been studied in patients with polycystic ovary syndrome (PCOS), but the relationship between PCOS and low-density lipoprotein (LDL) subclass pattern is not clear. A case-control study was designed to look into lipid differences, and LDL size was analyzed by a newly developed polyacrylamide tube gel electrophoresis method. Results indicated that only PCOS status and serum triglyceride levels were independently associated with LDL particle size. The apolipoprotein (Apo)A-I level was higher in PCOS patients with small dense LDL (sdLDL). PCOS seems to result in smaller LDL particle size and higher ApoA-I levels independent of triglyceride levels. After adjusting for triglyceride levels, other traits of insulin resistance syndrome (IRS) were not associated with LDL size phenotype, suggesting that the IRS-related sdLDL is linked most strongly to alterations in triglyceride levels.

Background: This study aimed to evaluate the blood homocysteine concentration in Arab patients with schizophrenia and assess its associations with clinical phenotypes of the disease., Subjects and Methods: Two age-matched groups of subjects were studied: (1) Healthy Controls, HC, n=165; (2) patients with schizophrenia, SZ: n=207. Each subject was evaluated with a standard questionnaire for age at disease onset, family history, disease severity and outcome. Plasma homocysteine levels (Hcys) were measured by immunoassay and serum levels of other biochemical parameters were measured by routine Autoanalyzer techniques., Results and Discussion: Group HC was heavier (body mass index, BMI) while SZ had greater waist-hip ratio (WHR) and plasma Hcys levels. In SZ, there were significant correlations between Hcys and BMI, triglycerides and HDL. Hcys levels in SZ were highest in the younger male patients., Conclusion: Schizophrenic patients have increased blood Hcys levels which correlate with components of the metabolic syndrome. Hcys levels were highest in the younger male patients and were not influenced by prognostic features of the disease.

The APOE gene locus has 3 major alleles, E3, E4 and E2, which variably influence coronary heart disease (CHD) risk. Plasma low-density lipoprotein (LDL) profile, another major CHD risk factor, is characterized on the basis of size and density into 2 main patterns: large buoyant LDL and small dense LDL. The latter has also been linked with increased CHD risk. This study investigates associations of specific APOE allelic patterns with LDL size and subfraction profiles in patients with CHD and healthy control subjects. We recruited 2 groups of male subjects: (A) 65 apparently healthy control subjects, median age, 39.0 years (range, 25.0-60.0 years); (B) 50 patients with CHD, median age, 54.0 years (range, 40.0-76.0 years). APOE genotypes were determined by validated polymerase chain reaction-restriction fragment length polymorphism methods, and LDL size and subfractions were assessed by a high-resolution, nongradient polyacrylamide gel electrophoresis technique (LIPOPRINT, Quantimetrix, Redondo Beach, CA). Lipid and other biochemical analyses were done by autoanalyzer techniques. The associations of specific APOE alleles and genotypes with LDL size and subfraction patterns were then assessed. As expected, patients with CHD had a worse atherogenic lipoprotein profile (waist-hip ratio, LDL, uric acid, and apolipoprotein B) than the controls. APOE genotype and allele frequencies were similar for both groups. In either group, median percent large buoyant LDL (pattern A) was greater in controls (51.0% vs 46.5%, P<.001) and percent small dense LDL (pattern B) was greater with CHD (9.0% vs 3.0%, P<.001). The latter also had smaller median particle size (26.5 vs 26.9 nm, P<.001). In controls, percent LDL pattern B was significantly lower with APOE2 than with APO non-E2 (4.0% vs 0.0%, P<.05); in patients with CHD, E2 patients had smaller particle size, and pattern B was significantly lower with non-E2 than with E2 (15.0 vs 8.0, P<.05). With respect to E4, control non-E4 had a smaller median percent LDL pattern B than E4; otherwise, there were no significant findings in relation to APOE type and LDL size and subfractions in both subject groups. These results confirm observations in other populations of increased levels of small dense LDL in patients with CHD. Although the APOE allelic pattern, especially APOE2, could be related to LDL subfraction profiles in control subjects, such associations could not be demonstrated in those with CHD.

Background: Insulin-like growth factors (IGFs) are believed to be important in brain development and repair following neuronal damage. It is also speculated that IGFs are involved in the association of foetal and pre-adult growth with schizophrenia (SZ)., Methods: The aim of this study was to assess levels of IGF-I, IGF-II and IGF binding protein (IGFBP)-3 and their associations in male Arab patients with SZ (n=53) and healthy control subjects (HC; n=52). Anthropometric and demographic data were collected for each subject for whom blood specimens were analysed for serum lipoproteins, apolipoprotein B (apoB), IGF-I, IGF-II and IGFBP-3., Results: The SZ group had lower serum total cholesterol, apoB and uric acid levels than the HC group (p<0.05). IGF-II levels were significantly higher in the SZ group (p=0.02) and correlated positively with levels of atherogenic lipoproteins--total cholesterol, low-density lipoprotein, apoB--and IGFBP-3. The pattern of correlations between the IGFs and the various parameters differed somewhat between the HC and SZ groups., Conclusions: These results demonstrate that IGF-II levels are increased in patients with SZ and show significant associations with atherogenic lipoproteins. We suggest a possible link between IGF-II metabolism and atherogenesis in SZ.

Objective: Insulin-like growth factors (IGF-I, IGF-II) and their binding protein (IGFBP-3) may be risk markers for coronary heart disease (CHD). This study aimed to assess the levels and determinants of the serum levels of IGF-I, IGF-II and IGFBP-3 in Arab patients with established CHD., Material and Methods: Two groups of subjects were matched for age, gender, BMI and waist-hip ratio (WHR): (i) CHD (n = 105), median age 51.0 (range 40.0-60.0) years; (ii) controls (n = 97) aged 49.0 (range 37.0-60.0) years. We measured fasting serum levels of glucose and lipoproteins (total cholesterol, triglycerides, LDL, HDL, apo B), insulin, HOMA-IR, IGF-I, IGF-II and IGFBP-3 and compared the results between groups. The effects of body mass and the metabolic syndrome (MS) on IGF levels were also examined, and linear correlations were sought between the various parameters., Results: The levels of IGF-I, IGF-II and IGFBP-3 were significantly lower (all p<0.01) for the CHD group than for the control group. These differences were not influenced by BMI or with the presence of MS. In CHD, there were no significant correlations between levels of IGF-I and IGF-II and age, BMI, WHR, lipoprotein concentrations and insulin sensitivity, although IGFBP-3 had weakly significant relationships with some of the lipoproteins., Conclusions: Levels of IGF-I, IGF-II and IGFBP3 are reduced in male Arab patients with CHD, and did not appear influenced by traditional CHD risk factors such as age, BMI, insulin sensitivity and presence of MS. Perturbations in the IGF/IGFBP-3 axis may be potential additional targets for pharmacological manipulation in CHD.

Objective: Factors responsible for the low incidence of clinical prostate cancer in the Arab population remain unclear, but may be related to differences in androgenic steroid hormone metabolism between Arabs and other populations, especially as prostate cancer is believed to be androgen dependent. We therefore measured the levels of serum androgenic steroids and their binding proteins in Arab men and compared results obtained with values reported for Caucasian populations to determine if any differences could at least partially account for differences in incidence of prostate cancer rates between the two populations., Methods: Venous blood samples were obtained from 327 unselected apparently healthy indigenous Arab men (Kuwaitis and Omanis) aged 15-79 years. Samples were also obtained from 30 Arab men with newly diagnosed prostate cancer. Serum levels of total testosterone (TT), sex hormone binding globulin (SHBG), derived free androgen index (FAI); adrenal C19 -steroids, dehydroepiandrosterone sulfate (DHEAS) and androstenedione (ADT) were determined by chemiluminescent immunoassay. Age specific reference intervals, mean and median for each analyte were determined. Frequency distribution pattern for each hormone was plotted. The reference range for hormones with normal distribution was mean +/- 2SD and 2.5-97.5% for those with non-normal distribution. The mean serum levels of the hormones in Arab men with prostate cancer were compared with values in healthy age-matched Arab men., Results: There was a significant decrease between the 21-29 years age group and the 70-79 years age group for TT (-38.77%), DHEAS (-70%), ADT (-36%) and FAI (-63.25%), and an increase for SHBG (+64%). The calculated reference ranges are TT (2.73-30.45 nmol/L), SHBG (6.45-65.67 nmol/L), FAI (14.51-180.34), DHEAS (0.9-11.0 micromol/L) and ADT (0.54-4.26 ng/mL). The mean TT, SHBG, DHEAS and ADT in Arab men were significantly lower than those reported for Caucasians especially in the 21-29 years age group. Arab men with newly diagnosed prostate cancer had higher serum TT (P < 0.7), ADT (P < 0.2), SHBG (P < 0.2) and lower DHEAS (P < 0.008) compared to aged matched controls., Conclusions: Serum TT, SHBG, DHEAS and ADT levels are significantly lower in Arab men compared to those reported for Caucasian men, especially in early adulthood. Arab men with newly diagnosed prostate cancer have higher circulating androgens compared to healthy controls. We suggest that low circulating androgens and their adrenal precursors in Arab men when compared to Caucasians may partially account for the relatively lower risk for prostate cancer among Arab men.

Introduction: Factors responsible for the low incidence of clinical prostate cancer (3-8/100,000 men/year) in the Arab population remain unclear, but may be related to changes in steroid hormone metabolism. We compared the levels of serum conjugated and unconjugated steroids between Arab and Caucasian populations, to determine if these can provide a rational explanation for differences in incidence of prostate cancer between the two populations., Patients/method: Venous blood samples were obtained from 329 unselected apparently healthy indigenous Arab men (Kuwaitis and Omanis) aged 15-80 years. Samples were also obtained from similar Arab men with newly diagnosed prostate cancer or benign prostatic hyperplasia (BPH). The samples were taken between 8:00 am and 12:00 noon. Serum levels of total testosterone, (TT), sex hormone binding globulin (SHBG), free androgen index (FAI); adrenal C19-steroids, dehydroepiandrosterone sulphate (DHEAS) and androstenedione (ADT) were determined using Immulite kits (Diagnostic Systems Laboratories Inc, Webster Texas, USA). The results obtained in Arab men were compared with those reported for similarly aged Chinese, German and White USA men., Results: In all four ethnic groups, median TT and FAI declined with age, while SHBG increased with age. However, the mean TT and SHBG was significantly lower (p < 0.01) and the FAI significantly higher in Arab men (p < 0.01) compared to German men only in 21-30 years age group. In the other age groups the levels of TT and SHBG were higher in the Germans but the differences were not statistically significant. In all the racial groups serum levels of DHEAS and ADT reached a peak by about 20 years of life, and then declined progressively. The mean DHEAS in American Caucasians aged 20-29 years was 11.4 micromol/l compared to 6.22 micromol/l in the Arabs (p < 0.001). The mean DHEAS in USA Caucasians aged 70-79 years was 2.5 micromol/l compared to 1.8 micromol/l (p < 0.03) in the Arabs. There was no significant difference in mean serum levels of DHEAS between German and USA men. Similarly, there was no significant difference in the level of the hormones between Arab and Chinese men. Arab men with newly diagnosed prostate cancer had high serum TT, SHBG and DHEAS compared to those without the disease., Conclusions: The mean TT and SHBG was significantly lower in Arab men compared to Caucasian men especially in early adulthood. Caucasians have significantly higher serum levels of the precursor androgens DHEAS and ADT especially in early adulthood compared to Arab men. These observations of low circulating androgens and their adrenal precursors in Arab men may partially account for the decreased risk for prostate cancer among Arab men.

Objectives: The purpose of this study was to determine the age-specific reference ranges for some important male sex steroid hormones, prostate-specific antigen (PSA), insulin-like growth factor-1 (IGF-1), and IGF binding protein-3 (IGFBP-3), for the Kuwaiti population., Subjects and Methods: Blood samples were taken from 398 consenting, fasting, healthy Kuwaiti males aged 15-80 years between 8.00 a.m. and 12.00 noon. The serum concentrations of total testosterone (TT), dehydro-epiandrosterone sulfate (DHEAS), androstenedione (ADT), sex hormone binding globulin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, PSA, IGF-1 and IGFBP-3 were determined. A distribution curve was plotted and age-specific reference levels were determined for each analyte. The reference interval for parameters with a normal distribution (Gaussian) was mean +/- 2 SD, while for the non-normal distribution (non-Gaussian), it was 2.5-97.5 percentile. The reference intervals for the analytes obtained from this study were compared with those suggested by the kit manufacturers and currently used by the Ministry of Health, Kuwait Laboratories (MOHKL)., Results: Serum IGFBP-3 and ADT had normal distribution while other analytes had non-normal distribution. The reference intervals from this study, manufacturers kit and MOHKL were as follows: TT 3-31, 9-60, 8-35 nmol/l; DHEAS 0.9-11, 1.0-7.3, 2.2- 15.2 micromol/l; ADT 0.5-4.3, 0.8-2.8, 2.0-9.2 nmol/l; LH 1-11, 0.8-7.6, 0.4-5.7 mIU/l; FSH 0.5-11, 0.7-11.1, 1.1-13.5 mIU/l; prolactin 42-397, 53-360, 80-230 nmol/l; IGF-1 41-542, 78-956, 71-261 ng/ml; IGFBP-3 88- 2,090, 900-4,000, 900-4,000 ng/ml, and PSA 0-3.1, 0-4, 0-4 ng/ml, respectively., Conclusion: These data indicate that for Kuwaitis lower reference ranges must be used for serum TT, DHEAS, ADT, IGFBP-3 and PSA. There is no need to change the currently used reference interval for FSH whereas higher values must be used for LH, prolactin, and IGF-1.

Background: The possible pathogenetic relationship between APOE genetic polymorphism and susceptibility to a variety of neurodegenerative disorders, including multiple sclerosis, is controversial. Previous studies have been conducted in Caucasian subjects, with little or no data on subjects from the Arabian Gulf. We compared the frequencies of specific APOE genotypes and alleles in patients with multiple sclerosis (MS) with frequencies observed in a healthy control Kuwaiti Arab population to relate APOE frequencies with specific identifiable clinical features of the disease., Methods: Two groups of subjects were studied: (i) 39 (17 M, 22 F) patients with clinical evidence of MS; (ii) 106 apparently healthy Kuwaitis recruited as control subjects. The MS patients had detailed clinical and laboratory evaluations, and APOE genotypes were determined in all the subjects (patients and controls) by validated PCR methods. Differences in frequencies of APOE alleles and associations of specific alleles with clinical features were assessed., Results: There were no significant differences in allele frequencies between patients and controls, although there was a statistically insignificant trend towards lower APOE2 allele frequency in the patients (p=0.09). There was a significant association of the APOE4 allele with female gender in the patients (p<0.05)., Conclusion: In Kuwaitis, a population with low MS prevalence, no statistically significant associations between APOE genetic polymorphism and susceptibility to MS could be established, but there was a trend towards a lower APOE2 frequency with MS and towards increased frequency of APOE4 in female patients and with severe disease.

Introduction: The incidence of clinical prostate cancer in the Arab population is among the lowest in the world. High serum IGF-1 level has been implicated as a possible risk factor for the development of prostate cancer in Caucasians. The purpose of this study was to determine serum IGF-1 and IGFBP-3 levels in healthy Arab men and in Arab men with newly diagnosed benign prostatic hyperplasia (BPH) and prostate cancer, and to compare these values with values reported in Caucasians., Patients and Methods: Subjects were recruited in two groups: (a) indigenous, healthy Arab men aged 15-90 y (n = 383); (b) Arab men with newly diagnosed prostate cancer (n = 30) or BPH (n = 40). Blood was obtained from fasting patients and volunteers, between 8:00 a.m. and 12:00 noon. The serum concentrations of IGF-1 and IGFBP-3 were determined using Immunoradiometric assay (IRMA) kits., Results: As in Caucasians, serum IGF-1 and IGFBP-3 levels declined with age in Arab men. The mean +/- s.d. of serum IGF-1 levels in healthy Arab men in the age group 15-20, 51-60, 61-70 y were lower (376.2 +/- 153.2, 134.9 +/- 105.7 and 89.6 +/- 48.4 ng/ml, respectively), compared to values reported for similarly aged Caucasians. Arab men with newly diagnosed prostate cancer had significantly higher serum IGF-1 level (P < 0.01) and lower IGFBP-3 levels (P < 0.01) compared to age-matched Arabs without the disease., Conclusions: Arab men have lower serum IGF-1 levels compared to Caucasians and this may be an important factor in the explanation of the low incidence of prostate cancer in the Arab population.

Background: APOE polymorphism is believed to confer susceptibility to coronary heart disease (CHD) and Alzheimer's disease. It is well known that patterns of APOE polymorphisms differ between populations and ethnic groups, although most of the data available so far have been in whites., Subject and Methods: We evaluated the frequencies of APOE genotypes and their relationships with serum levels of lipids, lipoproteins and apolipoproteins in two groups of Gulf Arab citizens: a control population of healthy voluntary blood donors (n=106), and a group of patients presenting to the lipid clinic for the first time with combined hyperlipidaemia (CH) (n=41). In both groups, fasting serum total cholesterol (TC), triglycerides (TG), HDL, LDL and apolipoprotein A1 and B levels were measured by routine autoanalyzer methods, and APOE genotyping was performed by validated PCR methods. The lipid and lipoprotein levels were related to the specific APOE allele frequencies., Results: Allele frequencies were 5.7% for *E2, 85.4% for *E3, and 9.0% for *E4 in the healthy blood donor group. An essentially similar pattern was seen in the patients with CH. This APOE allelic distribution conforms to patterns described in Chinese, whites and South Asians. In both the blood donor and CH groups there were no consistent links between specific APOE pattern and serum lipoproteins, as would have been predicted from APO *E2 and APO *E4 frequencies., Conclusions: We conclude that APOE allelic patterns in healthy Kuwaiti blood donors and a smaller group of patients with CH do not satisfactorily predict circulating blood levels of lipids and lipoproteins.

Background: An association between HLA antigens and susceptibility to multiple sclerosis (MS) has been established, especially in Caucasian populations. Such associations have not been as clearly defined in many Arab populations, where even the frequencies of specific HLA antigens remain unclear, Objective: The study was designed to (i) investigate the frequencies of HLA Class I and II antigens in Kuwaiti Arabs with MS, and; (ii) assess possible inter-relationships between HLA Class II antigens and such clinical phenotypic variables in MS as age at onset, gender, disease subtype and scale of disability., Subjects and Methods: HLA Class I (A, B, C) and Class II (DR, DQ) antigens' tissue-typing was performed by the standard complement-dependent microlymphocytotoxicity technique in two groups of age- and sex-matched Kuwaiti subjects: (i) 67 patients with definite MS (48 relapsing remitting, 19 relapsing-progressive) and (ii) 145 unrelated healthy controls. The frequencies of specific HLA types were then compared between patients with controls, and in the former, related to specified clinical parameters., Results: The frequencies for the Class I antigens: A9, A10, A19, A33, B5 and CW4 appeared higher with the presence of MS, although the numbers of positive subjects were rather low. For the Class II antigens, frequencies of DR4, DQ5, DQ6, DQ7 and DQ8 were increased while those for DR6 and DR1 were decreased in the patients with MS. HLA types DR15 and DR4 were present at higher frequencies in patients with a younger age at disease onset; DR15 also appeared more frequent in the female patients., Conclusion: There is a trend towards an association between HLA Class II antigens (DR4, DQ6, DQ7 and DQ8) and MS in Kuwaiti subjects. Additionally, it appeared that DR4 and DR15 were more frequent in females and those with an early onset of the disease. These patterns of HLA Class II determinants of susceptibility to MS differ from reports in some other populations, and may reflect the recognized variability in genetic influence on HLA and disease expression.

Background: The commonest cause of death in patients with end-stage renal disease (ESRD) on maintenance haemodialysis (MHD) is coronary heart disease (CHD). It has been suggested that dyslipidaemia, an important CHD risk factor, may be worsened by dialysis. This study evaluated changes in blood lipoproteins and apolipoproteins after dialysis in ESRD patients on MHD., Methods: The subjects were 57 (20 M, 37 F; 24 diabetic, 33 nondiabetic) patients with ESRD, aged 21-73 years, undergoing MHD at a major Dialysis Unit in Kuwait. Pre- and post-dialysis non-fasting blood samples were collected from each subject on the same day, and analyzed for plasma glucose, urate, triglycerides (TG), total cholesterol (TC), HDL, LDL and apolipoprotein (apo) A1 and B. Pre- and post-dialysis levels for each of the analytes were compared for the diabetic and non-diabetic subgroups of patients and linear correlations sought between Delta values (corresponding to differences between pre- and post-dialysis levels) of the lipoproteins and apolipoproteins., Results: There was a general trend towards significant increases in post-dialysis TC, HDL, LDL, and non-HDL levels in both sub-groups, and additionally for the non-diabetic, TG, apo A1 and apo B. The pre- to post-dialysis increases were essentially similar for the diabetic and non-diabetic groups-Diabetic: TC 14%, HDL 25%, LDL 19%, non-HDL 16%, apo A1 14%, apo B 10%; Non-diabetic: TC 20%, TG 29%, HDL 25%, LDL 26%, non-HDL 21%, apo A1 14%, apo B 14%. Generally, there were significant correlations between Delta values for the lipoproteins and apolipoproteins (r, 0.50-0.92) in both groups., Conclusion: Levels of atherogenic lipoproteins increase post-dialysis in diabetic and non-diabetic patients with ESRD and the changing levels of these lipoproteins correlate significantly with corresponding changes in levels of apolipoproteins. The increase in lipid levels is therefore related to retention of apo A1 and B with each dialysis. We speculate that, with repeated dialysis, dyslipidaemia may get progressively worse and further accentuate CHD risk., (Copyright 2004 Elsevier B.V.)

Background: The major components of metabolic syndrome are atherogenic dyslipidaemia (AD) and insulin resistance (IR), and both predict risk for atherosclerotic cardiovascular disease even in healthy individuals., Aims: To assess if, in a group of healthy young adult Arab subjects, a simple classification in high and normal scores on waist-hip ratio (WHR), body mass index (BMI) and waist circumference (WC) scales could predict atherogenic parameters for metabolic syndrome (AD, IR)., Subjects and Methods: The subjects [n = 177 (72 M, 105 F), aged 29.7 +/- 8.4 (SD) years], underwent physical evaluation, BP measurement and anthropometry [height (m), weight (kg), waist (WC) and hip circumference (HC, cm)]. The cut-off points for normal/high scores on the indices were: (1) BMI: 30 kg/m(2) (M and F); (2) WHR: 0.80 F, 0.95 M, and (3) WC: 90 cm F, 100 cm M). The biochemical indices measured on fasting serum were: (1) AD: total cholesterol (TC), triglycerides (TG), HDL, LDL, apo B, HDL/TC ratio, and (2) IR: insulin, urate, insulin/glucose ratio (IGR)., Results and Discussion: In the whole group of subjects, and in women separately considered, those with high indices (BMI, WHR, WC) had significantly increased levels of glucose, LDL, apo B, urate, mean BP, TG, insulin and IGR and lower values for HDL/TC ratio (all p < 0.05). In men, only urate, insulin and IGR levels were increased (p < 0.01) in the high-score groups. None of the indices showed any special superiority in describing the risk of AD or IR., Conclusion: In women, BMI, WHR and WC appeared equally good in identifying individuals at high risk of AD and IR while in men, these indices satisfactorily described the risk of IR but not of AD. It is important to re-emphasise the need to indicate gender distinctions in using anthropometry for CHD risk assessment., (Copyright 2004 S. Karger AG, Basel)

Objective: To report on stroke subtypes, associated risk factors and outcome in Kuwait., Methods: The records of 62 patients (30 male, 32 female) admitted with diagnosis of stroke to Kuwait Oil Company Hospital, Kuwait, a tertiary care hospital, during a 5-year period (1995-1999), were retrospectively reviewed., Results: Small artery infarction was the most common subtype and occurred in 37 subjects (59.7%); less common were atherosclerotic large artery strokes (19 patients, 30.6%) and strokes of cardio-embolic origin (6 patients, 9.7%). Identifiable risk factors or associated morbidities were hypertension (72.5%), diabetes mellitus (69.4%), ischaemic heart disease (14.5%), history of migraine (8.1%), lone atrial fibrillation (5.0%), and valvular heart disease (1.6%). The most important determinants of a deleterious 30-day outcome, as indicated by severe disability or death, were female gender, lack of use of anti-platelet drugs, presence of a large artery infarction stroke subtype, and cardio-embolic stroke., Conclusion: Prevalence of hypertension and diabetes is high among patients with stroke in Kuwait, with rates higher than those found in any previous reports from the Gulf region. Two unusual observations were that women had a rather high frequency of stroke, and infarction of the small artery was more common than that of the large artery. Outcome, as indicated by severe disability or death, was worse among women, elderly patients, and those with large artery atherosclerotic and cardio-embolic strokes. There is some evidence that such a deleterious outcome might be ameliorated with use of anti-platelet drugs., (Copyright 2003 S. Karger AG, Basel)

We investigated the potential relationship between hyperhomocysteinemia and the presence of coronary heart disease (CHD) and chronic complications in a consecutive series of 358 (156 men) Kuwaiti type 2 diabetic subjects. The median (2.5(th), 97.5(th) percentiles) fasting plasma concentration of total homocysteine (tHcy) in the patients was 10.2 (5.4, 19.1) micromol/l. Fasting tHcy concentration was significantly (p<0.001) higher among men [11.3 (7.1, 24.6) micromol/l] compared to women [8.8 (5.3, 16.3) micromol/l]. Of the 57 patients with a history of CHD and/or electrocardiographic (ECG) evidence of CHD, 9 (16%) had hyperhomocysteinemia (tHcy > or =15 micromol/l) compared to 8.3% (25 of 301) of patients without evidence of CHD. In univariate analysis, plasma tHcy concentration was significantly (p<0.01) higher in those diabetic subjects with history of CHD and/or abnormal ECG. Although hyperhomocysteinemia was more common in patients with microalbuminuria (15%) compared to patients with normoalbuminuria (12%), there was no significant association between hyperhomocysteinemia and the degree of albuminuria. After controlling for age and sex, multiple regression analyses showed significant associations of plasma tHcy concentration with glycated hemoglobin (p<0.05), plasma concentrations of creatinine (p<0.001) and apolipoprotein-B (p<0.05), but not with smoking, neuropathy or retinopathy. It seems that the association of hyperhomocysteinemia with diabetic microvascular complications is mediated by the confounding effect of other factors like age, sex and plasma creatinine concentration. In conclusion, we have found a univariate association between hyperhomocysteinemia and CHD but not with microalbuminuria, neuropathy and retinopathy. Although routine estimation of plasma homocysteine may be useful, the association with cardiovascular disease or microvascular complications in patients with type 2 DM deserves prospective studies.

The assessment of markers of systemic inflammation, such as C-reactive protein (CRP) and interleukin 6 (IL6), could be used to identify persons at high risk of coronary heart disease (CHD). This study evaluates the relationship of CRP and IL6 with CHD risk factors in patients with type 2 diabetes mellitus (DM) with CHD and age and sex matched type 2 DM controls without CHD. CRP, IL-6, total plasma homocysteine (tHcy), lipoprotein (a) [Lp(a)] and sialic acid (SA) were determined in 55 type 2 diabetic patients with CHD and 51 age- and sex-matched type 2 diabetic controls without CHD. Multivariate and logistic regression analyses were used to relate these markers with CHD risk factors. CRP (P=0.02) and tHcy (P=0.03) were significantly higher in patients with CHD compared with the control group even after correction for age and sex. IL6, Lp(a), SA and lipid parameters were not significantly different between the two groups of patients. After adjustment for potential confounders, the odds ratio (OR) for elevated CRP was 2.00 (95% confidence interval [CI], 1.12-3.58) (P=0.02) but the OR for IL6 was 3.41 95% CI, 0.70-17.17 (P=0.14). Partial correlation analyses of CRP and IL6 with other variables showed significant correlation of CRP with tHcy, and SA in patients with CHD only. Our results support the inclusion of CRP (high-sensitivity assay), in the risk assessment of diabetic subjects.

Background: Glycation and oxidative modification of lipoproteins enhance the uptake of these lipids by macrophages in the early stages of atherogenesis. Measurement of blood levels of modified LDL particles could thus constitute another useful modality in identifying subjects at high risk of coronary atherosclerosis (CHD)., Objective: To measure the glycated LDL level and assess its associations with other metabolic parameters in diabetic and nondiabetic hyperlipidaemic subjects attending a Lipid Clinic in Kuwait., Subjects and Methods: One hundred thirty-three hyperlipidaemic (HL) (72 nondiabetic (ND); 61 diabetic (D)) patients and 42 healthy control (HC) subjects had their fasting serum samples analyzed for glucose, total cholesterol (TC), triglycerides (TG), urate, HDL, LDL (by routine autoanalyzer methods), apolipoproteins A1 and B (by nephelometry), fructosamine (by spectrophotometry) and glycated LDL (gLDL) by ELISA., Results: The serum gLDL level was significantly higher in HL [D+ND] than in HC (p<0.001). Within the HL group, the DHL patients had higher levels than the NDHL [p<0.001]. These differences were maintained when the gLDL level was also expressed as a percentage of the apo B concentration. The gLDL level correlated positively (p<0.01) with those of glucose, TC, TG and LDL and negatively with HDL (p<0.05) in all the subjects as a whole, healthy and hyperlipidaemia [HC+HL]. In the HL (D+ND) group as a whole, gLDL correlated significantly only with glucose [p<0.01]. In group DHL, however, gLDL correlated significantly with glucose, fructosamine and LDL [all p<0.05]. As expected, fructosamine levels were highest in the DHL group. The significant correlations established between fructosamine and the different analytes measured in the different subject groups were essentially similar to those observed for gLDL, except for the finding of persistent significant negative correlations of fructosamine with LDL in all the subject groups., Conclusions: (i) Serum gLDL levels are increased in hyperlipidaemic patients and are further increased with diabetes, suggesting that the significant glycation of LDL occurs in all hyperlipidaemic patients irrespective of their glycaemic status. (ii) The significant correlation of gLDL with glucose and fructosamine in diabetic patients would suggest its potential utility as another index of medium term glycaemic control. (iii) gLDL is easily measurable and its values could provide additional information in ascertaining an individual's aggregate CHD risk.

Objective: To evaluate the role of serum troponin I (Tnl) estimations in the early risk stratification of patients with acute coronary syndromes (ACS) subsequently diagnosed as acute myocardial infarction (AMI) or unstable angina (UA)., Subjects and Methods: Blood samples were collected from 86 patients admitted to the Coronary Care Unit of the Mubarak Al-Kabeer Hospital, Kuwait, with a diagnosis of ACS on admission (Tnl-1) and after 8 h (Tnl-2) and 16 h (Tnl-3). Blood was also collected from 38 age-matched healthy controls for comparison. Serum Tnl was measured by paramagnetic particle chemiluminescent immunoassay., Results: Serum Tnl of < 0.05 ng/ml, corresponding to the 99th percentile, was established for healthy subjects. Patients diagnosed as UA had a 99th percentile Tnl-1 value of about 0.30 ng/ml. The best specificity and sensitivity for ACS was obtained for Tnl-2; indeed, Tnl-2 > 0.3 ng/ml gave a > 80% certainty of diagnosis of AMI. Also, Tnl-2 < 0.3 ng/ml in ACS patients was approximately 80% sensitive for the diagnosis of UA but relatively nonspecific (approximately 40%). Specificity for Tnl-2 for the diagnosis of UA improved to about 90% by narrowing the diagnostic range to 0.05-0.3 ng/ml. Tnl values in UA increased by < 100% at 8 h, while in AMI, this increase was up to 1,000%., Conclusion: In the evaluation of ACS, admission and 8-hour serum Tnl < 0.05 ng/ml is probably not cardiac in origin; serum Tnl > 0.3 ng/ml on admission and increasing rapidly by 8 h is likely AMI, and serum Tnl > 0.05 and < 0.3 ng/ml on admission with a mild increase by 8 h is likely due to UA.

About 15% of the adult Kuwaiti population has type 2 diabetes and over 50% are hyperlipidaemic by current diagnostic criteria. Not surprisingly, coronary heart disease (CHD) is the leading cause of death in Kuwait. Reports from coronary care units in Kuwait suggest that 40-80% of the CHD patients were diabetic and 50-80% hyperlipidaemic. The pattern worldwide is similar. International guidelines have therefore consistently recognised diabetes as a major risk factor for CHD. In our Lipid Clinic population in Kuwait, about 30% are diabetic. The commonest lipid abnormalities seen in Kuwaiti diabetic patients, as elsewhere, are hypertriglyceridaemia with low HDL levels and variable LDL levels. About 75% of the subjects had either mixed hyperlipidaemia or predominant hypertriglyceridaemia. There are possibly some compositional changes in LDL in the diabetic subjects in that there were important differences in the statistical relationships between LDL and HDL and their respective apolipoproteins - apo B and apo A-1 in diabetic as compared to non-diabetic subjects. Other important observations made in diabetic subjects in Kuwait are: (i) similar serum Lp (a) levels and pattern of apo(a) polymorphism with non-diabetic subjects, with no demonstrable relationship between serum levels of Lp(a) and insulin/insulin sensitivity, although with CHD, Lp(a) levels were increased; (ii) diabetic hyperlipidaemic subjects had elevated PAI-1 levels with significant correlations between blood PAI-1 and insulin levels suggesting underlying insulin resistance (syndrome X). Various landmark trials of cholesterol-lowering therapies in the prevention of CHD have consistently demonstrated near-normalization of the increased CHD risk in diabetes. Our experience in Kuwait suggests that diabetic patients and others with mixed hyperlipidaemia benefit from tight glycaemic control, appropriate advice on diet and exercise with regular reinforcement by continuing contact with professional dietitians and regular availability of drugs where prescribed. Often, it is the regular compliance with medication that is important, rather than the specific medication used particularly where HMG CoA reductase inhibitors (statin drugs) are not always available. A useful guideline for management of dyslipidaemia in diabetes is suggested., (Copyright 2002 S. Karger AG, Basel)

Background: The limited data available on the role of insulin on maternal-fetal transport of amino acids prompted us to undertake this study., Methods: Transport kinetics of a model amino acid, alpha-aminoisobutyric acid (AIB) was investigated in perfusion of isolated human placental lobules in vitro in non steady-state conditions and the effect of therapeutic dose of insulin was assessed in parallel series of perfusions. National Culture and Tissue Collection medium diluted with Earle's buffered salt solution was used as the perfusate and tritiated water was used as the reference marker for comparison., Results: In five successful perfusions with insulin, differential transport rate indices of AIB for 10, 25, 50, 75 and 90% of efflux fractions in the fetal venous outflow averaged 0.76, 1.03, 1.02, 1.09, 1.04 and 1.03 times those of reference values, respectively. The indices differed significantly than in controls for 10, 25 and 50% efflux fractions, but not in the case of 75 and 90% efflux values. The AIB transport fraction (TF), expressed as percentage of injected maternal dose, averaged 29.4 +/- 5.4% and 38.7 +/- 6.2% of the corresponding reference marker value in control and insulin series, respectively. With regards to the pharmacokinetic transport parameters, the absorption and elimination rates of the amino acid were significantly higher in the study group than in the control., Conclusion: We conclude that insulin, in physiological and therapeutic doses, stimulates maternal-fetal AIB transport in vitro, in the perfused human placental lobule.

Serum lipoprotein(a) [Lp(a)], a risk factor for coronary heart disease (CHD) in some nondiabetic populations, is largely under genetic control and varies among ethnic and racial groups. We evaluated serum Lp(a) concentration and its relationship with traditional CHD risk factors (age, sex, smoking, hypertension, dyslipidemia) as well as stage of diabetic nephropathy in 345 type 2 diabetic patients. Lp(a) concentration was skewed with median (2.5th, 97.5th percentiles) of 25.0 (8.1, 75.7) mg/dl. Twenty-three of 55 (41.8%) patients with CHD had increased (>30 mg/dl) Lp(a) compared with 102 of 290 (35.1%) patients without CHD (P=.35). Twelve of 27 (44.4%) female patients with CHD had increased Lp(a) compared to 11 of 28 (39.3%) males (P=.70). Lp(a) was significantly (P<.05) higher in females than males, but the logistic regression analysis showed significant association of Lp(a), LDL-C, and duration of diabetes mellitus (DM) with CHD in male patients only. Although female patients with CHD and macroalbuminuria had significantly (P<.05) higher Lp(a) than normoalbuminuric female patients without CHD, no such association was found in males and no significant association was found between Lp(a) and the degree of albuminuria. Partial correlation analysis controlling for age, sex, and BMI showed significant correlation of Lp(a) with total cholesterol only (P=.03) and no correlation was found with other lipid parameters. Multiple regression analysis did not show significant associations of Lp(a) with standard CHD risk factors, HbA(1c), and plasma creatinine. This study is in agreement with studies in other populations, which showed that Lp(a) may not be an independent risk factor for CHD in patients with DM. However, as Lp(a) could promote atherogenesis via several mechanisms, follow-up studies in our patients will confirm if increased Lp(a) concentration can partly account for the poorer prognosis when diabetic patients develop CHD.

The aim of this study was to assess parameters of renal function and other determinants of plasma homocysteine in type 2 diabetic patients without coronary heart disease (CHD). Fasting plasma homocysteine, serum cystatin C and serum creatinine were determined in 183 (75 men, 108 women) Type 2 diabetic patients without clinical evidence of CHD. Creatinine clearance was calculated and parameters such as blood pressure, body mass index (BMI), and glycated haemoglobin (HbA(1c)) were assessed. The urine albumin:creatinine ratio was used to classify patients as normo-, micro- or macroalbuminuric. One hundred and ten patients were normoalbuminuric, 67 patients were microalbuminuric and six patients were macroalbuminuric. There was no statistically significant difference in plasma homocysteine concentration between patients with normoalbuminuria and microalbuminuria. There was a trend towards increasing plasma homocysteine with decreasing glomerular filtration rate (GFR) (r=-0.46; P<0.0001). There was statistically significant correlation between plasma homocysteine and age (r=0.37), serum cystatin C (r=0.47), and serum creatinine (r=0.56). Plasma homocysteine concentration was significantly higher in patients with BMI<30 kg/m(2) and showed significant inverse correlation with weight (r=-0.16; P=0.03) and body mass index (r=-0.24; P=0.001). Homocysteine and serum creatinine were significantly higher in males than females and higher in smokers than non smokers but was not associated with glycemic control and duration of diabetes. In conclusion, elevated homocysteine concentration in patients with type 2 DM without CHD is related to age, gender, smoking, BMI and GFR. Follow up studies will provide further information on the association between hyperhomocysteinemia and the development of cardiovascular disease.

Serum total sialic acid is a marker of the acute phase response. Elevated levels have also been associated with cardiovascular disease in the general Caucasian population and especially in Type 2 diabetic subjects. The purpose of this study was to estimate serum total sialic acid concentrations among Kuwaiti Type 2 diabetic subjects and to investigate its association with macro and microvascular diabetes-related complications in that population. Serum total sialic acid levels were estimated by an enzymatic spectro-photometric assay in two groups of subjects: (i) 358 Kuwaiti Type 2 diabetics (156 men and 202 women) referred for their annual evaluation to the specialised diabetic clinic at the main university teaching hospital in Kuwait, and (ii) 47 healthy age and sex matched non-diabetic Kuwaiti control population (13 men and 34 women). Serum sialic acid levels were significantly higher (P<0.001) among the diabetic patients (mean+/-S.D.) (81.2+/-13.2 mg/dl) compared to the non-diabetic controls (66.9+/-11.0 mg/dl). Kuwaiti diabetic women had significantly higher concentrations compared to diabetic men (85.2+/-12.1 vs. 75.9+/-13.0 mg/dl, P<0.001). Among the controls there was no significant gender difference in sialic acid levels of women, (68.3+/-11.6 mg/dl) versus men (63.2+/-8.2 mg/dl). The gender difference in the diabetic patients was unrelated to the degree of obesity. Significant correlations were found between serum total sialic acid concentrations and such cardiovascular risk factors as plasma levels of apolipoprotein B, low density lipoprotein cholesterol, triglycerides and uric acid in the diabetic subjects. Furthermore, there was a significant elevation in serum total sialic acid concentrations with increasing urinary albumin excretion, P<0.001, but not with retinopathy or neuropathy.

Benign hypergammaglobulinemic purpura of Waldenström (HGPW) is an uncommon cause of non-thrombocytopaenic purpura that may create diagnostic difficulties. The presence of constitutional symptoms associated with prominent immunological abnormalities may raise alarm, leading to extensive and often unnecessary investigations. This report describes 3 young women with HGPW. Clinical features were characterised by recurrent episodes of bilateral asymmetrical palpable purpuric lesions on the lower extremities that were precipitated by a prolonged increase in hydrostatic pressure (e.g. prolonged standing, tight stockings etc.) associated with constitutional features. In one patient the condition was secondary to Sjögren's syndrome with type IV renal tubular acidosis. Laboratory abnormalities included a persistently elevated erythrocyte sedimentation rate, marked polyclonal hypergammaglobulinemia, and high titers of rheumatoid factor and anti-nuclear antibody of the anti-SSA (anti-Ro)/anti-SSB(anti-La) subsets. This topic is reviewed briefly with the emphasis that in its 'primary' form this condition could be considered a 'benign' systemic immunoinflammatory disease that requires neither extensive investigations nor any aggressive form of therapy. Greater awareness of HGPW may increase the frequency of its diagnosis, especially in the patient group with non-thrombocytopenic purpura or the so-called cutaneous vasculitic syndromes with 'palpable purpura'.

It is well recognized that blood lipoprotein A [Lp(a)] levels constitute an important risk factor for atherosclerotic vascular disease. In some populations, mainly Caucasian, Lp(a) levels and coronary heart disease (CHD) risk are determined by the pattern of apolipoprotein a [apo(a)] polymorphism. It is currently unclear if these observations apply to other populations and ethnic groups. The aim of the current study is to determine to what extent known apo(a) polymorphisms associate with development of CHD in a Kuwaiti Arab population. Serum Lp(a) levels were measured by enzyme-linked immunosorbent assay and apo(a) isoforms determined by a high-resolution sodium dodecyl sulphate/agarose gel electrophoresis with immunoblotting in two groups of Kuwaiti subjects: healthy controls (n = 140) and subjects with CHD (n = 140). Blood lipids and anthropometric parameters were also determined in these subjects by standard methods. Serum Lp(a) levels were greater in those with CHD than in those in the healthy group (P < 0.001). There was no consistent trend in the pattern of serum Lp(a) levels found with specific apo(a) isoforms in either group of subjects. There was, therefore, no simple relationship between the isoform pattern (and number of kringle-IV repeats) and serum Lp(a) concentration, unlike in certain other populations. Additionally, almost identical proportions of subjects in either group had single-banded (homozygous, approximately 70%), double-banded (heterozygous, approximately 23%) and no-band (null, approximately 7%) phenotypes. The distribution of the five identified isoforms (F, S1, S2, S3 and S4) also was almost identical for both groups of subjects, whether homozygous or heterozygous, and whether classified into fast-moving (F, S1 and S2) or slow-moving (S3 and S4) isoforms. We conclude that the frequency and pattern of distribution of apo(a) phenotypes did not differ significantly between healthy control Kuwaiti Arab subjects and those with CHD. It is thus unlikely that an individual's apo(a) phenotype can predict both serum Lp(a) level and risk for CHD, irrespective of race and/or ethnic grouping.

Elevated plasminogen activator inhibitor-1 (PAI-1) levels have been described in some populations to associate with hyperinsulinaemia in the metabolic syndrome which predisposes to coronary heart disease (CHD). This association, if consistently present, could provide more evidence for a synergistic role for insulin resistance and altered fibrinolysis in the pathogenesis of CHD. To test the hypothesis further therefore, we explored the relationships between the fasting levels of insulin and PAI-1 and lipids in groups of non-diabetic Arab subjects classified as: A: normolipidaemic (n = 148); B: hyperlipidaemic: (n = 99), subdivided into - C: normotensive (n = 71) and D: hypertensive (n = 28); and E: patients with CHD (n = 12). In Group A, fasting insulin (FI) was 7.2+/-(SD) 3.4 mU/l, PAI-1 30.6+/-9.7 ng/ml, both levels significantly lower (P < 0.05) than in Group B as a whole (FI 9.7+/-5.2, PAI-1 36.9+/-10.6), or as normotensive Group C (FI 9.4+/-5.4, PAI-1 36.7+/-10.3) or hypertensive Group D (FI 10.9+/-4.8, PAI-1 37.2+/-11.5). These values were highest in the hyperlipidaemic hypertensive Group D. There were no significant differences relative to the hyperlipidaemic phenotype of predominant hypercholesterolaemia, hypertriglyceridaemia or mixed hyperlipidaemia. PAI-1 (34.7+/-13.8) and FI (7.0+/-2.4) levels in Group E with CHD were similar to those of Group A but lower than values seen in Groups B, C and D. Consistent positive correlations (r = 0.32-0.41, P <0.01) were demonstrable in all the groups between PAI-1 and triglycerides levels. There were also significant correlations between insulin and PAI-1 (r = 0.20, P<0.1) in all the subjects (grouped as a whole, n = 259) and in normolipidaemic Group A (r = 0.29, P < 0.01) but not in any of the hyperlipidaemic groups or in patients with CHD. This study therefore suggests that levels of insulin and PAI-1 are increased in hyperlipidaemic subjects, particularly when also hypertensive. The further observation of significant correlations between insulin and PAI-1 levels only in normolipidaemic subjects and not those who were hyperlipidaemic or with CHD is at variance with observations in Caucasians in whom strong positive correlations between insulin and PAI-1 had suggested that elevated PAI-1 levels should constitute one more component of the metabolic syndrome which strongly predisposes to CHD. Whether this is a racial variation or an artifact of the insulin/PAI-1 assay methodology is unclear and deserves further study.

Background/aim: This study was performed to comparatively evaluate the results obtained for low-density lipoprotein (LDL) cholesterol concentrations by either a newly described direct method or the Friedewald equation in subjects with and without chronic renal disease., Methods: Fasting plasma was obtained from a total of 169 subjects, 105 with normal renal function (including 53 hyperlipidaemic) and 64 with chronic renal disease (nephrotic syndrome and/or chronic renal failure; including 40 hyperlipidaemic patients), and analyzed for LDL cholesterol using the Friedewald equation and a direct LDL assay method., Results: The Friedewald equation and the direct LDL cholesterol assay correlated well with each other (r = 0.79-0.90 in all subjects with plasma triglyceride, TG, levels greater than or less than 4.0 mmol/l and with and without chronic renal disease and/or hyperlipidaemia, all p < 0.0001). The values for LDL cholesterol, however, tended to be higher with the direct measurement. This mean difference was trivial in hyperlipidaemic subjects with (8.5%) and without (7.1%) normal renal function (both p < 0.05), but could be clinically significant in those with TG >4.0 mmol/l (mean difference 18%, p < 0.001). Indeed, bias plots confirmed this observation of wider negative bias for Friedewald estimation in these moderately hypertriglyceridaemic subjects., Conclusion: For most routine laboratories the options immediately available for assessment of lipid levels are the Friedewald equation or the direct measurement. The Friedewald equation and the direct assay method for LDL cholesterol are about equally good for assessment of the LDL status in patients with chronic renal disease and plasma TG <4.0 mmol/l. Where there are restraints on laboratory budgets, it would appear appropriate that the more expensive direct assay method be restricted to cases in whom plasma TG >4.0 mmol/l or to patients who, for whatever reason, are unable to produce fasting samples.

Plasma levels of lipoprotein(a) [Lp(a)], tissue plasminogen activator (tPA) and plasminogen activator inhibitor type 1 (PAI-1) were assessed in addition to anthropometry and levels of glucose, total cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and apo A1 and B in 73 patients (36 men and 37 women) with primary hyperlipidaemia (group NDHL) in Kuwait. Lp(a) levels (212 mg L-1, 8-600 mg L-1, median and range) were similar to those obtained in a matched group of 32 non-insulin-dependent diabetes mellitus (NIDDM) patients with hyperlipidaemia (218 mg L-1, 50-610 mg L-1) and slightly higher, although not significantly so (P = 0.06), than levels seen in 68 healthy normolipidaemic control subjects (182 mg L-1, 70-488 mg L-1). tPA levels (8.4 ng mL-1, 3.8-18.4 ng mL-1, median and range) in group NDHL were lower than in the diabetic group (11.4 ng mL-1, 5.2-14.2 ng mL-1) but higher than in the healthy control subjects (7.4 ng mL-1, 2.8-12.6 ng mL-1). PAI-1 levels in group NDHL (40.4 ng mL-1, 8.6-55 ng mL-1, median and range) were higher than in the control subjects (32.5 ng mL-1, 14.6-46.4 ng mL-1) but lower than in diabetic patients (43.8 ng mL-1, 15.6-55 ng mL-1). Hyperlipidaemia phenotype (hypercholesterolaemia or hypertriglyceridaemia) did not influence tPA and PAI-1 levels, but Lp(a) levels were significantly lower with hypertriglyceridaemia. Gender, cigarette smoking and racial origin (Kuwaitis, other Arabs or South Asians) did not affect Lp(a), tPA and PAI-1 levels, but tPA levels were higher in postmenopausal subjects. Low-density lipoprotein (LDL) levels (whether in total cholesterol or as apo B) correlated significantly (P < 0.05) with Lp(a) levels. tPA levels were correlated with age and the plasma levels of glucose and uric acid (P < 0.05); this correlation with glucose may explain the high levels associated with diabetes, whereas the age association might account not only for the differences observed between group NDHL and the younger control group but also for the higher levels in the postmenopausal women. PAI-1 levels correlated with tPA and triglyceride (TG) levels in the groups of subjects (normo- and hyperlipidaemic). In the normolipidaemic control group, the significant associations of tPA and PAI-1 were with body mass, expressed as the body mass index or the waist-hip ratio. These results suggest that different factors influence the plasma levels of the prothrombotic factors Lp(a), tPA and PAI-1 in healthy control subjects and in patients with hyperlipidaemia. In the latter, hyperlipidaemia phenotype, age, glycaemic status and uric acid levels are important determinants of the levels of these prothrombotic variables, whereas in the healthy, young control population, body mass was the single important association with tPA and PAI-1.

We assessed the prevalence of coronary heart disease (CHD) risk factors including insulin resistance in 500 (205 males, 295 females) healthy elderly (age > 55 years) indigenous, low socioeconomic group Yorubas residents in either an urban slum (n = 240) or a rural town (n = 260) in southwestern Nigeria. Anthropometric indices, blood pressure and fasting plasma levels of glucose, lipids, insulin and insulin resistance were measured. The results indicated that: (i) gross obesity (4.4%), diabetes (1.6%), hyperlipidaemia (0.2%) and cigarette smoking (4.8%) were relatively uncommon in the population, although the prevalence of hypertension (30%) was higher than previously reported from this population; (ii). the subjects had a relatively high prevalence of multiple CHD risk factors (about 20% had > 4 risk factors), an observation considered paradoxical in view of the reportedly low CHD prevalence in this population; (iii) these CHD risk factors (increased body mass and blood pressure (BP), hyperinsulinaemia and insulin resistance) were more prevalent in the women and in urban residents; (iv) hyperinsulinaemia (20%) and insulin resistance (35%) were common in the population, and were associated, on regression analyses, to such other CHD risk factors as BP and body mass, particularly in women, suggesting, as in Caucasians, that insulin resistance could be an important index of CHD risk; and (v) the excess of multiple CHD risk factors in the women, is due at least in part, to their increased tendency to obesity (8%) and reduced physical activity (83%). This study concludes that: (i) despite the high prevalence of multiple risk factors in this population, CHD prevalence is low, indicating the supremacy of such major risk factors as diabetes and hyperlipidaemia (relatively uncommon here) in the development of CHD; and (ii) potentially the greatest CHD risk is in the elderly women especially if relatively overweight, physically inactive and resident in an urban centre. While further confirmatory studies are necessary in younger subjects and across societal socioeconomic strata, our results nonetheless suggest that attempts to maintain the CHD prevalence at low levels in this population should include efforts directed at reducing excess body weight particularly in women, and advice on maintenance of a traditional diet to keep lipid levels and diabetes prevalence low.