Risk factors associated with alterations in carotid intima-media thickness in hypertension: baseline data from the European Lacidipine Study on Atherosclerosis

BACKGROUND: The possibility that calcium antagonists exert an anti-atherosclerotic action at least partly independently of the blood-pressure-lowering effect is supported by results of a large number of experimental studies and can now be investigated by quantitative B-mode ultrasound imagining of the carotid artery walls. DESIGN: The European Lacidipine Study on Atherosclerosis (ELSA) is a prospective, randomized, double-blind, multinational trial comparing effects of 4-year treatment based on the long-acting, highly lipophilic calcium antagonist lacidipine with those of treatment based on the beta-blocker atenolol on the development of carotid artery wall alterations in patients (aged 45-75 years) with mild-to-moderate hypertension (systolic blood pressure 150-210 mmHg and diastolic blood pressure 95-115 mmHg). While the intervention study is progressing, this article summarizes baseline data obtained from the whole cohort of 2259 patients randomly allocated to treatment. METHODS: Baseline ultrasound data were obtained from two replicate examinations performed shortly before random allocation to treatment by certified sonographers at 23 referral centres and read at the ultrasound coordinating centre at the Wake Forest University School of Medicine. Intima-media thickness was measured at up to 12 different sites in the carotid artery tree and expressed as the mean of the maxima at these sites (Mmax), the mean of the maxima at four sites in the distal common carotid artery and bifurcation (CBMmax) and the maximum intima-media thickness (Tmax). Baseline demographic and clinical measurements were performed by investigators in 410 peripheral clinical units and 24 h ambulatory blood pressure monitorings read and validated by members of a centralized unit at the University of Milan. The statistical analysis centre at the Technische Universit?t München received and analysed all baseline data, by calculating means +/- SD, medians and ranges and performing correlation (Spearman correlation coefficients) and multiple regression analyses. RESULTS: Prevalence of carotid artery wall alterations among the hypertensive patients randomly allocated to treatment in the ELSA was very high: 82% had Tmax > or = 1.3 mm ('plaques' according to protocol) and 17% had Tmax > or = 1.0 and < 1.3 mm ('thickening'), with a median of two plaques per patient. We found significant correlations between ultrasound measurements and the following demographic and clinical variables: age, sex, systolic blood pressure and pulse pressure (both clinic and ambulatory), concentrations of total, high-density lipoprotein and low-density lipoprotein cholesterol and triglycerides, smoking habit and duration of hypertension. We found no significant correlation to diastolic blood pressure and glucose concentration. A multiple regression analysis indicated significant variables in the following rank order: age, 24 h ambulatory pulse pressure, sex, low-density lipoprotein cholesterol concentration, triglyceride concentration, smoking and clinic systolic blood pressure. CONCLUSIONS: Analysis of baseline data from the ELSA has shown that there is an extremely marked prevalence of carotid artery wall alterations among mild-to-moderate, middle-aged hypertensive patients. In addition to age, systolic blood pressure and pulse pressure, particularly if they are accurately measured by ambulatory monitoring, play a major role, somewhat greater than those of sex, low-density lipoprotein cholesterol concentration and smoking, in influencing intima-media thickness.     

Cardiovascular risk factors for early carotid atherosclerosis in the general population: the Edinburgh Artery Study

BACKGROUND: Recent attempts to identify cardiovascular risk factors affecting early-stage carotid atherosclerosis, measured by ultrasonographically assessed intima-media thickness, have been inconclusive. OBJECTIVE: To study the relationship between traditional cardiovascular risk factors and intima-media thickness. METHODS: Ultrasonic evaluation of the intima-media thickness of the common carotid artery was included in the 5-year follow-up examination of participants of the Edinburgh Artery Study. We had valid readings of intima-media thickness for 1106 men and women aged 60-80 years. Information on a range of cardiovascular risk factors had been collected during the baseline examination. RESULTS: For men, in addition to age, lifetime smoking (measured in terms of pack years) was the only cardiovascular risk factor associated with increased intima-media thickness (P< or = 0.01) in the univariate analysis. Both systolic blood pressure (P < or = 0.001) and the high-density lipoprotein (HDL: total cholesterol ratio (P < or = 0.01) were correlated with intima-media thickness for women. When all the variables had been included in a multivariate analysis, pack years of smoking and the HDL:total cholesterol ratio were associated with early atherosclerotic development in men. In an equivalent analysis for women, alcohol consumption, systolic blood pressure and the HDL:total cholesterol ratio were associated with intima-media thickness. CONCLUSION: These data suggest that risk factors affecting intima-media thickness differ for men and women. Further sex-specific analyses of prospective population studies are required in order to clarify the role of 'traditional' cardiovascular risk factors in the early stages of carotid atherosclerosis.     

Insulin sensitivity in familial hypercholesterolemia

Insulin resistance is found in association with obesity, non-insulin-dependent diabetes mellitus, and essential hypertension, which are all risk factors for atherosclerotic cardiovascular disease. Furthermore, hyperinsulinemia has been reported in familial combined hyperlipoproteinemia and endogenous hypertriglyceridemia. Finally, relatively high serum triglyceride and low high-density lipoprotein (HDL) cholesterol concentrations invariably accompany hyperinsulinemia. Whether insulin sensitivity is affected by the isolated presence of high levels of serum low-density lipoprotein (LDL) cholesterol has not been clearly established. We studied 13 subjects with heterozygous familial hypercholesterolemia (FHC) and 15 normocholesterolemic subjects selected to be free of any other known cause of insulin resistance. Thus FHC patients and controls had normal body weight and fat distribution, glucose tolerance, blood pressure, and serum triglyceride and HDL cholesterol concentrations, but were completely separated on plasma LDL cholesterol concentrations (6.05 +/- 0.38 v 3.27 +/- 0.15 mmol/L, P < .0001). Fasting plasma levels of glucose, insulin, free fatty acids (FFA), and potassium and fasting rates of net carbohydrate and lipid oxidation were superimposable in the two study groups. During a 2-hour euglycemic (approximately 5 mmol/L) hyperinsulinemic (approximately 340 pmol/L) clamp, whole-body glucose disposal rates averaged 30.4 +/- 2.3 and 31.1 +/- 3.0 mumol.kg-1 x min-1 in FHC and control subjects, respectively (P = 0.88). The ability of exogenous hyperinsulinemia to stimulate carbohydrate oxidation and energy expenditure and suppress lipid oxidation and plasma FFA and potassium levels was equivalent in FHC and control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Human evolution

BACKGROUND: Apheresis of low-density lipoprotein (LDL) is an effective lipid-lowering treatment in hypercholesterolemic patients who have coronary artery disease and are refractory to drugs. More aggressive lipid-lowering therapy may further slow the progression of atherosclerosis. OBJECTIVE: To compare the effect of LDL apheresis and simvastatin therapy with the effect of simvastatin therapy alone on the progression of peripheral vascular disease. DESIGN: Open, randomized, single-center study. SETTING: University hospital. PATIENTS: 42 men with primary hypercholesterolemia (total cholesterol level > 8.0 mmol/L) and extensive coronary atherosclerosis. INTERVENTION: Biweekly apheresis of LDL plus simvastatin, 40 mg/d (n = 21), or simvastatin, 40 mg/d (n = 21), for 2 years. MEASUREMENTS: Lipid and lipoprotein levels, changes in hemodynamically significant stenoses in the aortotibial tract (measured by ankle:arm systolic blood pressure ratio combined with Doppler spectrum analysis of the femoral artery), and changes in the mean intima-media thickness of three carotid artery segments. RESULTS: Mean baseline LDL cholesterol levels decreased from 7.8 to 3.0 mmol/L in the apheresis and simvastatin group and from 7.9 to 4.1 mmol/L in the simvastatin-only group; mean lipoprotein(a) levels decreased from 57.0 to 44.5 mg/dL (change, -19%) in the former group and increased from 38.4 to 44.5 mg/dL (change, 15%) in the latter group. In the apheresis group, the number of patients with hemodynamically significant stenoses in the aortotibial tract decreased from 9 to 7; in the simvastatin-only group, the number increased from 6 to 13 (P = 0.002). Mean intima-media thickness decreased by a mean +/- SD of 0.05 +/- 0.34 mm in the apheresis group and increased by 0.06 +/- 0.38 mm in the simvastatin-only group (P < 0.001). According to multiple regression analysis, changes in apolipoprotein B, total cholesterol, and lipoprotein(a) levels accounted for changes in the aortotibial tract (R2 = 0.36); changes in lipoprotein(a) and apolipoprotein A1 levels accounted for changes in the intima-media thickness of the carotid artery (R2 = 0.49). CONCLUSIONS: Aggressive lipid lowering with simvastatin and LDL apheresis decreased the intima-media thickness of the carotid artery and prevented an increase in the number of hemodynamically significant stenoses in the lower limbs. Therapy with simvastatin alone did not prevent progression of carotid or aortotibial vascular disease.     

Metabolic and endocrine effects of the desogestrel-containing oral contraceptive Mircette

OBJECTIVE: The purpose was to evaluate the metabolic effects of Mircette (brand of desogestrel/ethinyl estradiol and ethinyl estradiol), a low-estrogen, desogestrel-containing oral contraceptive. STUDY DESIGN: Women taking Mircette were evaluated to determine its effects on lipid profiles (n = 74), carbohydrate metabolism (n = 25), and endocrine parameters (n = 53). RESULTS: During cycles 3 and 6 of Mircette treatment, changes from baseline included mean increases in serum triglycerides and very low-density lipoprotein cholesterol ranging between 50% and 60%. Smaller mean increases were observed at these time points in high-density lipoprotein cholesterol subfraction 2 (range between 17% and 25%), total cholesterol (<10%), high-density lipoprotein cholesterol (range between 10% and 15%), and high-density lipoprotein cholesterol subfraction 3 (range between 9% and 13%), with only nominal changes (<6%) in low-density lipoprotein cholesterol and lipoprotein. Patients receiving Mircette showed no mean changes in fasting plasma glucose or serum insulin levels but did have modest increases in glucose and insulin levels after a glucose challenge. Mircette treatment suppressed follicle-stimulating hormone, luteinizing hormone, 17beta-estradiol, and progesterone to levels consistent with inhibition of ovulation and increased concentrations of thyroid- and cortisol-binding globulins. CONCLUSIONS: Overall, Mircette treatment was associated with expected effects on the pituitary-ovarian axis, triglycerides, and serum binding proteins; a modest decline in glucose tolerance; and a favorable effect on lipid profiles as a result of increases in total high-density lipoprotein cholesterol and high-density lipoprotein cholesterol subfraction 2 in the absence of changes in total cholesterol or low-density lipoprotein cholesterol.     

Current zinc intake and risk of diabetes and coronary artery disease and factors associated with insulin resistance in rural and urban populations of North India

OBJECTIVE: To determine the association between current zinc intake and prevalence of coronary artery disease (CAD) and diabetes as well as factors associated with insulin resistance. DESIGN, SUBJECTS AND METHODS: In this cross sectional survey, 3575 subjects, aged 25 to 64 years, including 1769 rural (894 men. 875 women) and 1806 urban (904 men, 902 women) subjects were studied. The survey methods included questionnaires for 7-day food intake record, physical examination, and electrocardiography using World Health Organization criteria. RESULTS: The prevalence of CAD, diabetes and glucose intolerance was significantly higher among subjects consuming lower intakes of dietary zinc. There was a higher prevalence of hypertension, hypertriglyceridemia and low high-density lipoprotein cholesterol levels which showed significant upward trend with lower zinc intakes. Serum lipoprotein (a) and 2-hour plasma insulin levels also were associated with low zinc intake. Multivariate logistic regression analysis after adjustment for age showed that zinc intake and CAD were inversely associated. Serum zinc (odds ratio:men 0.77, women 0.57), serum triglycerides (men 0.86, women 0.81), blood pressure (0.83 men, women 0.76), diabetes mellitus (men 0.90, women 0.85), central obesity (men 0.88, women 0.87), glucose intolerance (men 0.66, women 0.57) and low high-density lipoprotein cholesterol (men 0.72, women 0.70) were significant risk factors for CAD (explained by tertiles of zinc status) in urban subjects. These associations were not observed in rural subjects. CONCLUSION: Lower consumption of dietary zinc and low serum zinc levels were associated with an increased prevalence of CAD and diabetes and several of their associated risk factors including hypertension, hypertriglyceridemia and other factors suggestive of mild insulin resistance in urban subjects.     

Treatment for all: the computer as a patient assistant

Hypertension and hyperlipidemia are common and powerful risk factors for cardiovascular disease. Although they may coexist in the same individual by chance, the syndrome of insulin resistance is the common mechanism in many individuals, in whom there is a specific lipoprotein profile of small, dense, low-density lipoprotein particles, reduced plasma high-density lipoprotein cholesterol levels, and increased plasma triglycerides. This lipoprotein profile may be exacerbated by diuretics or beta-blockers. Initial management of the insulin resistance syndrome is by weight loss and dietary measures. Optimum antihypertensive and lipid-lowering drug strategy remains to be established.     

Prevalence of hyperapobetalipoproteinemia and other lipoprotein phenotypes in men (aged < or = 50 years) and women (< or = 60 years) with coronary artery disease

The prevalence and clinical characteristics of hyperapobetalipoproteinemia (hyperapoB) and other phenotypes of dyslipoproteinemia were examined in 99 men (aged < or = 50 years) and 104 women (< or = 60 years) undergoing elective diagnostic coronary arteriography. HyperapoB was the most common phenotype (34%) associated with premature coronary artery disease (CAD). Only 20.2% of patients with CAD had a normal lipoprotein phenotype. The significant odds ratios for CAD were as follows: hypertriglyceridemic hyperapoB 17.45 (p < 0.0001), type IV 6.54 (p = 0.0001), type IIa 4.73 (p = 0.008), normotriglyceridemic hyperapoB 2.54 (p = 0.03) and type IIb 8.73 (p = 0.05). The strong association of hypertriglyceridemic hyperapoB with CAD reflected the multiplicative effect of increased low-density lipoprotein apolipoprotein B and endogenous hypertriglyceridemia, and was independent of the effects of age, sex, diabetes mellitus, systemic hypertension, body mass index and cigarette smoking. The ratio of apolipoprotein B to A-1 was better than those of low-density to high-density lipoprotein cholesterol and total to high-density lipoprotein cholesterol at discriminating dyslipidemic phenotypes from normal. Obesity was increased approximately 1.5 to two-fold in the hypertriglyceridemic phenotypes, diabetes was more prevalent in hypertriglyceridemic hyperapoB (6.8-fold; p < 0.001) and type IV (4.4-fold; p = 0.02), and hypertension was increased 1.5- to twofold in most dyslipidemic groups. The data indicate that hyperapoB and endogenous hypertriglyceridemia both contribute to the risk of premature CAD.     

Effects of 17 alpha-dihydroequilenin sulfate on atherosclerotic male and female rhesus monkeys

OBJECTIVES: Our purpose was to determine the effects of 17 alpha-dihydroequilenin on plasma lipid and lipoprotein, glucose, and insulin concentrations; coronary artery vasomotor function; and reproductive organ and mammary gland proliferation in atherosclerotic male and female rhesus macaques. STUDY DESIGN: Fifty adult female and 33 adult male rhesus macaques were randomized to treatment by lifetime dietary cholesterol exposure and ratio of total plasma cholesterol to high-density lipoprotein cholesterol. The female treatment groups were intact female controls (n = 9), ovariectomized controls (n = 16), ovariectomized plus 0.3 mg/kg/day 17 alpha-dihydroequilenin (n = 17) and ovariectomized plus subcutaneous estradiol (n = 7). The male treatment groups were control (n = 16) and 1.25 mg/kg/day 17 alpha-dihydroequilenin (n = 17). Treatment lasted 5 weeks. Longitudinal assessments of plasma lipid and lipoprotein and glucose and insulin concentrations were performed. Coronary artery vasomotor function was assessed by quantitative coronary angiography 1 week after initiation of treatment. Morphologic and immunohistochemical assessments of proliferation index values of reproductive organs and mammary glands were done at necropsy. RESULTS: 17 alpha-Dihydroequilenin prevented endothelium-dependent vasoconstriction in males (p < 0.05) and ovariectomized females (p < 0.08). 17 alpha-Dihydroequilenin treatment increased plasma apolipoprotein A-1 concentrations (p < 0.05) and lowered fasting insulin concentrations (p < 0.05) without changing fasting plasma glucose concentrations in males. 17 alpha-Dihydroequilenin had no other effects on plasma lipid and lipoprotein concentrations in either males or females. It had no trophic effects on uterus, endometrium, or breast. There was no effect on either prostatic or testicular weight. CONCLUSION: 17 alpha-Dihydroequilenin may represent a single-agent hormone therapy for reduction of ischemic hear disease risk for both menopausal women and men. It has no apparent trophic effects on reproductive organs or mammary glands of female and male rhesus macaques.     

Schizophrenia and delusional disorder in older age: community prevalence, incidence, comorbidity, and outcome

Obesity is associated with dyslipidaemia characterised by increased fasting triglyceride and decreased high-density lipoprotein (HDL) concentrations. Causes for obesity-associated dyslipidaemia include insulin resistance, excessive caloric intake, increased free fatty acid production and disturbances in the counter-regulatory hormones. We examined the relationships between lipid parameters and obesity before and after adjustment of insulin resistance in 902 Hong Kong Chinese men. After adjustment for age, smoking and insulin resistance, increasing body mass index (BMI) and waist-to-hip ratio (WHR) remained closely associated with increased concentrations of triglyceride and apolipoprotein B (apo B), increased ratios between low-density lipoprotein (LDL) and HDL (LDL/HDL), and that between apo B and LDL (apo B/LDL), increased fasting and 2-h plasma glucose and insulin, as well as decreased concentrations of HDL, HDL2 and apolipoprotein A-I (apo A-I). On stepwise multiple regression analysis using age, BMI, WHR, insulin resistance and fasting plasma glucose as independent variables, BMI and WHR were the major determinants for the variance of triglyceride, HDL and its subfractions, LDL/HDL, apo B and apo B/LDL. Age was the most important predictor for total cholesterol and LDL. Insulin resistance only explained less than 1% of the variance in triglyceride and apo B. This was compared to a variance between 10 and 16% in these parameters as explained by BMI and/or WHR. In conclusion, obesity is associated with dyslipidaemia in Chinese men, characterised by increased plasma triglyceride, apo B, LDL/HDL, apo B/LDL, and decreased HDL, HDL2 and apo A-I concentrations. Obesity independent of insulin resistance, in particular central adiposity as reflected by increased WHR, was the most important independent variable for many of these lipid abnormalities. Our results emphasised the multifactorial linkage between obesity and dyslipidaemia.     

Influence of inoculation site of combined oil-adjuvanted vaccine on the antibody response in chickens

In this study, we evaluated the relationship between resistance to insulin-mediated glucose disposal and hematocrit (Hct) and hemoglobin (Hgb) concentrations in 150 normal, healthy volunteers: 100 men and 50 women. Insulin resistance was defined as the steady-state plasma glucose (SSPG) concentration at the end of a 180-minute infusion of somatostatin, insulin, and glucose. Since the steady-state plasma insulin (SSPI) concentrations are similar in all individuals, the SSPG concentrations provide a direct measure of insulin resistance: the higher the SSPG, the more insulin-resistant the subject. The results indicated that SSPG was significantly (P < .001) related to Hct and Hgb in both men and women, with correlation coefficients (r) ranging from 0.38 to 0.43. A series of other variables were also related to Hct and Hgb, including blood pressure, plasma glucose and insulin responses to oral glucose, and plasma triglyceride and high-density lipoprotein (HDL) concentrations. When multiple regression analysis was used to evaluate these relationships, the only variables that were consistently found to be associated with Hct and Hgb were insulin resistance and plasma insulin response to oral glucose. Thus, these results suggest that Hct and Hgb concentrations be added to the cluster of variables related to insulin resistance and compensatory hyperinsulinemia.     

Fasting insulin and apolipoprotein B levels and low-density lipoprotein particle size as risk factors for ischemic heart disease

CONTEXT: Epidemiological studies have established a relationship between cholesterol and low-density lipoprotein cholesterol (LDL-C) concentrations and the risk of ischemic heart disease (IHD), but up to half of patients with IHD may have cholesterol levels in the normal range. OBJECTIVE: To assess the ability to predict the risk of IHD using a cluster of nontraditional metabolic risk factors that includes elevated fasting insulin and apolipoprotein B levels as well as small, dense LDL particles. DESIGN: Nested case-control study. SETTING: Cases and controls were identified from the population-based cohort of the Quebec Cardiovascular Study, a prospective study conducted in men free of IHD in 1985 and followed up for 5 years. PARTICIPANTS: Incident IHD cases were matched with controls selected from among the sample of men who remained IHD free during follow-up. Matching variables were age, smoking habits, body mass index, and alcohol consumption. The sample included 85 complete pairs of nondiabetic IHD cases and controls. MAIN OUTCOME MEASURES: Ability of fasting insulin level, apolipoprotein B level, and LDL particle diameter to predict IHD events, defined as angina, coronary insufficiency, nonfatal myocardial infarction, and coronary death. RESULTS: The risk of IHD was significantly increased in men who had elevated fasting plasma insulin and apolipoprotein B levels and small, dense LDL particles, compared with men who had normal levels for 2 of these 3 risk factors (odds ratio [OR], 5.9; 95% confidence interval [CI], 2.3-15.4). Multivariate adjustment for LDL-C, triglycerides, and high-density lipoprotein cholesterol (HDL-C) did not attenuate the relationship between the cluster of nontraditional risk factors and IHD (OR, 5.2; 95% CI, 1.7-15.7). On the other hand, the risk of IHD in men having a combination of elevated LDL-C and triglyceride levels and reduced HDL-C levels was no longer significant (OR, 1.4; 95% CI, 0.5-3.5) after multivariate adjustment for fasting plasma insulin level, apolipoprotein B level, and LDL particle size. CONCLUSION: Results from this prospective study suggest that the measurement of fasting plasma insulin level, apolipoprotein B level, and LDL particle size may provide further information on the risk of IHD compared with the information provided by conventional lipid variables.     

The diabetes mellitus regimen

Some patients with essential hypertension manifest increased urinary albumin excretion (UAE). Hypertensive patients with microalbuminuria manifest abnormal circadian variation of blood pressure, increased serum levels of LDL-cholesterol and lipoprotein(a), a greater rise of serum insulin in response to an oral glucose tolerance test, and greater thickness of the carotid artery than patients without microalbuminuria. A 7 year follow-up of 141 hypertensive patients, 54 with microalbuminuria and 87 without microalbuminuria, we observed 12 cardiovascular events in patients with microalbuminuria and only 2 events in the patients with normal urine albumin excretion (P < 0.0002). Creatinine clearance decreased more in patients with microalbuminuria than in those with normal UAE. In conclusion, hypertensive individuals with microalbuminuria manifest a greater incidence of cardiovascular events and more decline in renal function than patients with normal UAE. We propose that measurements of UAE may be a useful marker for cardiovascular risk in patients with essential hypertension.     

Effect of cilazapril therapy on glucose and lipid metabolism in patients with hypertension

The effects of long-term monotherapy with cilazapril, an angiotensin-converting enzyme inhibitor, on blood pressure, glucose tolerance, and serum lipid profiles were prospectively investigated in 66 patients with hypertension: 23 with normal glucose tolerance and 43 with glucose intolerance (including 9 patients with non-insulin-dependent diabetes mellitus). The levels of plasma glucose, serum insulin, serum lipids, glycated hemoglobin A(lc) (Hb A(lc)), and fructosamine were determined before and during long-term (mean +/- SD, 26.2 +/- 1.2 weeks) therapy with cilazapril. A 75-g oral glucose tolerance test was performed before and during treatment. Significant reductions in both systolic and diastolic blood pressures in both patient groups were maintained during the study. Neither fasting nor post-glucose load venous plasma glucose levels were altered in either group of patients, and no patient with normal glucose tolerance developed diabetes mellitus during the study. There was no significant change in the insulinogenic index (delta serum insulin/delta venous plasma glucose at 30 minutes post-glucose load) in either group, and glucose intolerance was slightly improved with significant reductions (P < 0.01) in Hb A(lc) and fructosamine in the patient group with impaired glucose tolerance. Serum total cholesterol (TC), low-density lipoprotein cholesterol, and triglyceride levels were significantly (P < 0.01) decreased and high-density lipoprotein cholesterol levels increased in patients with hypercholesterolemia (TC levels > or = 5.69 mmol/L). These results suggest that long-term cilazapril therapy may improve glucose and lipid metabolism in hypertensive patients with impaired glucose tolerance. Cilazapril also appears to be useful as an antihypertensive agent for hypertensive patients with either impaired glucose tolerance or hypercholesterolemia.     

Repeat consultations in pediatric hospital emergencies

OBJECTIVE: To assess the extent of early atherosclerotic changes of the carotid arteries in young patients with familial hypercholesterolaemia (FH) detected as increased intima-media thickness (IMT), and to determine the relations between IMT and some clinical and blood variables such as lipid and lipoprotein(a) (Lp(a)) concentration and haemostatic factors. DESIGN: The IMT of the carotid bifurcation, the proximal 1 cm of the internal carotid artery, and the distal 1 cm of the common carotid artery was determined in all subjects using B mode ultrasonography. Blood lipids, fasting glucose, and several haemostatic variables were also analysed. SUBJECTS: 28 patients with FH (12 males and 16 females aged 11 to 27 years, one homozygote, 27 heterozygotes) and 28 sex and age matched normolipidaemic healthy subjects. RESULTS: The mean carotid IMT (the average of six measurements of the maximum far wall IMT in the three carotid segments on each side) was significantly greater in patients with FH than in controls (mean (SD) 0.71 (0.15) v 0.49 (0.08) mm, P < 0.001). In all subjects, the mean IMT was significantly correlated with total cholesterol (r = 0.59), low density lipoprotein (LDL) cholesterol (r = 0.60), triglycerides (r = 0.27), and systolic blood pressure (r = 0.47). No correlation was found between the mean IMT and Lp(a), fibrinogen, tissue plasminogen activator, and plasminogen activator inhibitor 1. CONCLUSIONS: The majority of young patients with FH have a greater intima-media thickness of the carotid arteries than healthy subjects. Since the individual susceptibility of patients with FH to increased LDL cholesterol is different, B mode ultrasonography could provide a useful tool to identify those who are more likely to develop premature atherosclerotic disease.     

Associations of serum and dietary magnesium with cardiovascular disease, hypertension, diabetes, insulin, and carotid arterial wall thickness: the ARIC study. Atherosclerosis Risk in Communities Study

The objective of this study was to examine the relationships of serum and dietary magnesium (Mg) with prevalent cardiovascular disease (CVD), hypertension, diabetes mellitus, fasting insulin, and average carotid intimal-medial wall thickness measured by B-mode ultrasound. A cross-sectional design was used. The setting was the Atherosclerosis Risk in Communities (ARIC) Study in four US communities. A total of 15,248 participants took part, male and female, black and white, aged 45-64 years. Fasting serum Mg, lipids, fasting glucose and insulin were measured; as was usual dietary intake by food frequency questionnaire and carotid intima-media thickness by standardized B-mode ultrasound methods. The results showed that serum Mg levels and dietary Mg intake were both lower in blacks than whites. Mean serum Mg levels were significantly lower in participants with prevalent CVD, hypertension, and diabetes than in those free of these diseases. In participants without CVD, serum Mg levels were also inversely associated with fasting serum insulin, glucose, systolic blood pressure and smoking. Dietary Mg intake was inversely associated with fasting serum insulin, plasma high density lipoprotein-cholesterol, systolic and diastolic blood pressure. Adjusted for age, race, body mass index, smoking, hypertension, Low density lipoprotein-cholesterol, and field center, mean carotid wall thickness increased in women by 0.0118 mm (p = 0.006) in diuretic users and 0.0048 mm (p = 0.017) in nonusers for each 0.1 mmol/l decrease in serum Mg level; the multivariate association in men was not significant. In conclusion, low serum and dietary Mg may be related to the etiologies of CVD, hypertension, diabetes, and atherosclerosis.     

Relationship between fasting plasma glucose, atherosclerosis risk factors and carotid intima media thickness in non-diabetic individuals

We analysed the relationship between fasting plasma glucose, carotid intima media thickness and some atherosclerosis risk factors in 307 non-diabetic individuals. Male (n = 120) and female subjects (n = 187) with a familial history of Type II diabetes mellitus and/or obesity and hyperlipoproteinaemia were examined in the age group 40-70 years. Plasma triglycerides, total and high-density-lipoprotein cholesterol, plasminogen activator inhibitor were measured by conventional methods. Specific insulin, pro-insulin and C-peptide were measured by specific enzyme immunoassay. Intima media thickness increased in quintiles for fasting plasma glucose in men, but not in women. There was a rise of triglycerides, body mass index, waist to hip ratio, plasminogen activator inhibitor, true insulin, proinsulin, C-peptide and a decrease of high-density-lipoprotein cholesterol in quintiles for fasting plasma glucose. Fasting plasma glucose was found to be significantly positively correlated to intima media thickness, body mass index, waist to hip ratio, haemoglobin A1c, insulin, C-peptide, triglycerides, plasminogen activator inhibitor and significantly negatively correlated to high density lipoprotein cholesterol. However, the correlation of fasting plasma glucose to intima media thickness was no longer significant after adjustment for age and sex. After adjustment for age and sex intima media thickness was significantly correlated to body mass index, total cholesterol, triglycerides, albuminuria and inversely correlated to high-density-lipoprotein cholesterol. In multivariate analysis age, male sex, high-density-lipoprotein cholesterol and total cholesterol were significant determinants of intima media thickness. Our data suggest that a weak association exists between fasting plasma glucose and intima media thickness, which may be mediated by a clustering of risk factors in the upper range of non-diabetic fasting plasma glucose level with a central role for dyslipidaemia.     

'True' fasting serum insulin level, insulin resistance syndrome and coronary artery disease

BACKGROUND: Increased fasting serum insulin level not associated with hypoglycemia is considered to be a practical indicator of the insulin resistance syndrome, a frequent risk factor for atherosclerosis in industrialized countries. However, in most studies, insulin was measured by using antibodies which cross-react with proinsulin and 31/32, 32/33 split products of insulin. We re-examined the correlations between the insulin resistance syndrome and 'true' fasting serum insulin level. METHODS: We studied 242 post-menopausal women (age 63 +/- 8 years), a population in whom insulin resistance syndrome is particularly frequent. Serum insulin was measured by a recent specific microparticle immunoassay. RESULTS: There was a significant correlation between elevated 'true' fasting serum insulin level and various constituents of the insulin resistance syndrome, such as obesity, dyslipidemia (hypertriglyceridemia, increased apolipoprotein B and decreased high-density lipoprotein cholesterol and apolipoprotein A1 concentrations), increased serum glucose, uric acid levels, and plasminogen activator inhibitor type I concentration, as well as increased frequency of diabetes. There was also a correlation between insulin level and various manifestations of coronary artery disease: patients in the highest quartile of 'true' insulin level had significantly more entirely occluded coronary arteries than in the lowest one. Similarly, in the highest insulin quartile more patients had occluded arteries with lumen diameter stenoses greater than 50% (P < 0.05) and more of them had history of previous myocardial infarction approaching the level of significance (P = 0.0587) than in the lowest one. Most of these correlations were also noted in nondiabetic people. CONCLUSIONS: An increase of 'true' fasting serum insulin level is a useful practical index to identify patients with the insulin resistance syndrome exposed to increased risk of coronary artery disease.     

Effects of varying carbohydrate content of diet in patients with non-insulin-dependent diabetes mellitus

OBJECTIVE: To study effects of variation in carbohydrate content of diet on glycemia and plasma lipoproteins in patients with non-insulin-dependent diabetes mellitus (NIDDM). DESIGN: A four-center randomized crossover trial. SETTING: Outpatient and inpatient evaluation in metabolic units. PATIENTS: Forty-two NIDDM patients receiving glipizide therapy. INTERVENTIONS: A high-carbohydrate diet containing 55% of the total energy as carbohydrates and 30% as fats was compared with a high-monounsaturated-fat diet containing 40% carbohydrates and 45% fats. The amounts of saturated fats, polyunsaturated fats, cholesterol, sucrose, and protein were similar. The study diets, prepared in metabolic kitchens, were provided as the sole nutrients to subjects for 6 weeks each. To assess longer-term effects, a subgroup of 21 patients continued the diet they received second for an additional 8 weeks. MAIN OUTCOME MEASURES: Fasting plasma glucose, insulin, lipoproteins, and glycosylated hemoglobin concentrations. Twenty-four-hour profiles of glucose, insulin, and triglyceride levels. RESULTS: The site of study as well as the diet order did not affect the results. Compared with the high-monounsaturated-fat diet, the high-carbohydrate diet increased fasting plasma triglyceride levels and very low-density lipoprotein cholesterol levels by 24% (P < .0001) and 23% (P = .0001), respectively, and increased daylong plasma triglyceride, glucose, and insulin values by 10% (P = .03), 12% (P < .0001), and 9% (P = .02), respectively. Plasma total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels remained unchanged. The effects of both diets on plasma glucose, insulin, and triglyceride levels persisted for 14 weeks. CONCLUSIONS: In NIDDM patients, high-carbohydrate diets compared with high-monounsaturated-fat diets caused persistent deterioration of glycemic control and accentuation of hyperinsulinemia, as well as increased plasma triglyceride and very-low-density lipoprotein cholesterol levels, which may not be desirable.     

Clinical, haematological and molecular studies in patients with chromosome translocation t(7;11): a study of four Chinese patients in Taiwan

We examined the association between the polymorphism of the apolipoprotein E (apoE) and the ACE genes and the intima-media thickness (IMT) of the carotid and femoral arteries measured using ultrasonography. The values of IMT of each artery were significantly higher in NIDDM patients (n = 356) than in control subjects (n = 235). The E4 allele or the D allele did not affect clinical characteristics, including age, fasting plasma glucose, total cholesterol, HDL cholesterol, LDL cholesterol, or blood pressure, in NIDDM or control subjects. No difference in the carotid IMT value was noted among the apoE genotypes in control or diabetic subjects. The carotid IMT was significantly higher in diabetic patients with the DD genotype (1.200 +/- 0.586 mm) than in those with the II genotypes (0.990 +/- 0.364 mm). Neither the E4 allele nor the D allele affected the femoral IMT in control or diabetic subjects. Multiple regression analysis demonstrated that the carotid IMT of NIDDM patients was associated with age, the D allele, and LDL cholesterol but not with the E4 allele, whereas that of control subjects was associated with age, sex, systolic blood pressure, LDL cholesterol, and HDL cholesterol, inversely. These results suggested that the E4 allele was not associated with the carotid or femoral IMTs, but that the D allele was statistically associated with carotid IMT in NIDDM patients but not control subjects. However, since the association was weak (2.3% explanatory power), its biological significance remains to be determined.