Microalbuminuria, an integrated marker of cardiovascular risk in essential hypertension

This paper reviews the existing epidemiological and clinical evidence about the relationships of non-diabetic microalbuminuria with cardiovascular risk factors such as elevated blood pressure (BP), systolic particularly, cardiac hypertrophy, adverse metabolic status, smoking habits, elevated angiotensin II levels, endothelial dysfunction, acute and perhaps subclinical inflammation. Because of that unique property of reflecting the influence of so many clinically relevant parameters, microalbuminuria may legitimately be defined as an integrated marker of cardiovascular risk, an unique profile among the several prognostic predictors available to stratify risk in hypertensive patients. Recent cohort studies also showed associations with cardiovascular morbidity and mortality independently from conventional atherogenic factors. This behaviour, whose understanding still needs further elucidation, suggests to measure albuminuria and to screen patients at a higher absolute risk in whom preventive treatment is expected to be more beneficial than in those with a lower absolute risk.     

Low-grade inflammation and microalbuminuria in hypertension

Background- Albuminuria and C-reactive protein (CRP), a marker of systemic low-grade inflammation, are frequently elevated in essential hypertension and predict cardiovascular prognosis independent of conventional risk factors. However, in spite of their potentially important links, the interrelationships between the 2 parameters have not been explored in depth in hypertensive patients. METHODS AND RESULTS: Albuminuria (the mean of 3 overnight urine collections), high-sensitive CRP (hs-CRP), 24-hour blood pressure (BP), weight, lipids, poststimulative (75 g PO) plasma glucose, insulin, and insulin sensitivity by the homeostasis model assessment model were evaluated in 220 never treated, nondiabetic, uncomplicated essential hypertensive men. Albuminuria > or =15 microg/min was defined as microalbuminuria and hs-CRP values above and below median (2.3 mg/L) as high and low, respectively. Concentric left ventricular hypertrophy was diagnosed by echocardiography, and a full-blown metabolic syndrome was identified in presence of hypertension and at least 3 of following: obesity, subclinical hyperglycemia, low high-density lipoprotein (HDL) and high triglycerides. Microalbuminuria was present in 54 patients, 29 with high hs-CRP characterized by higher 24-hour systolic BP, postload glucose, body mass index, lower HDL cholesterol, more frequent metabolic syndrome, concentric LVH, and active smoking than those with either isolated microalbuminuria (n=27) or normoalbuminuria. CONCLUSIONS: Microalbuminuria accompanied by evidence of subclinical inflammation is a strong correlate of metabolic abnormalities in essential hypertension and identifies a patient subset at very high cardiovascular risk. In contrast, isolated microalbuminuria may represent a distinct pathophysiological condition characterized by a more benign profile and possibly a better prognosis.     

Subclinical atherosclerosis in rheumatoid arthritis in India

OBJECTIVE: Patients with rheumatoid arthritis (RA) have high cardiovascular morbidity and mortality as compared to the general population. Indians are also at increased risk of developing early and severe atherosclerotic coronary artery disease. Carotid intima-media thickness as measured by ultrasound is a validated surrogate marker of atherosclerosis. We studied the prevalence of subclinical atherosclerosis in Indian patients with RA. METHODS: Common carotid IMT (CCA IMT) was measured at the level of carotid bifurcation along with fasting lipid profile in 57 RA patients and 45 age and sex matched controls. Values of mean CCA IMT above mean + 2 SD of the control group were defined as abnormal IMT. Variables of disease activity and severity were measured in RA patients. Patients and controls with known traditional cardiovascular risk factors were excluded from the study. Student t test and chi-square test for proportion were used for statistical analysis. A logistic regression analysis was done to find out independent predictors of abnormal IMT. RESULTS: Nineteen RA patients (33.3%) and 2 controls (4.44%) had abnormal IMT values. RA patients had significantly increased mean CCA IMT (0.558 +/- 0.137 mm) as compared to controls (0.416 +/- 0.002 mm; p < 0.0001). Age > or = 42 years, duration of disease > or= 6 years, and tender joint count > or = 5 predicted increased risk of having abnormal CCA IMT in a logistic regression analysis. CONCLUSION: One-third of Indian RA patients had subclinical atherosclerosis. Age and tender joint count were independent predictors of abnormal CCA IMT.     

Non-diabetic microalbuminuria, endothelial dysfunction and cardiovascular disease

Subclinical increases in albuminuria (microalbuminuria) predict morbid events, but the reasons for that are still not understood in full. This paper reviews the existing evidence regarding the relationships of non-diabetic microalbuminuria and cardiovascular disease, the underlying assumption being that endothelial dysfunction contributes both to atherosclerotic macrovascular disease and renal microvascular disease of which albuminuria is a marker. Much data support that concept, and suggest a preferential link with endothelial activation in response to acute and subclinical inflammatory stimulation, although further studies are needed to establish the exact cause-effect mechanisms. Epidemiological studies also show associations with cardiovascular events, and some recent prospective results also indicate the power of microalbuminuria to predict risk independently from conventional atherogenic factors. Thus, microalbuminuria might be considered as an integrated marker of cardiovascular risk sensitive to systemic vascular status in addition to other parameters such as blood pressure levels, glucose metabolism, smoking habits, a profile rather unique among the prognostic predictors available to stratify risk in hypertensive patients.     

Plasma leptin is independently associated with the intima-media thickness of the common carotid artery.

OBJECTIVE: To investigate whether intima-media thickness (IMT) of the common carotid artery (CCA), an early marker of asymptomatic atherosclerosis, is significantly and independently associated with plasma concentrations of leptin, an adipose tissue hormone that has recently been proposed as a cardiovascular risk factor in obese patients. DESIGN: Cross-sectional sample of normal-weight and obese men and women. SUBJECTS: One-hundred and twenty healthy subjects (52 men and 68 women), aged 18-45 y and with a wide range of BMI, were recruited for the study. MEASUREMENTS: Fasting plasma leptin concentrations and the IMT of the CCA were measured in all subjects. Leptin concentrations were measured by radioimmunoassay and the IMT of the CCA was quantified by high resolution B-mode ultrasound imaging. Central fat (measured by waist circumference), smoking habits, blood pressure, insulin sensitivity (measured by the insulin tolerance test), and fasting plasma glucose, insulin and lipid pattern (cholesterol, HDL-cholesterol, triglycerides, LDL-cholesterol) were also measured. RESULTS: IMT of the CCA was positively correlated with log leptin concentrations (P<0.005 in men and P<0.001 in women), body mass index (P<0.001 in men and women), waist circumference (P<0.001 in men and women), age (P<0.001 in men and P<0.05 in women), and negatively associated with insulin sensitivity in both sexes (P<0.05). IMT was also directly correlated with cholesterol (P<0.05), LDL-cholesterol (P<0.01) and systolic blood pressure in men (P<0.05), and with diastolic blood pressure levels in women (P<0.05). When a multiple linear regression model was used without body mass index (BMI), the correlation between leptin and IMT was maintained in both men (P<0.01) and women (P<0.005), independent of age, insulin sensitivity, smoking habits, systolic blood pressure, fasting glucose, triglycerides, cholesterol, LDL-cholesterol and HDL-cholesterol. By contrast, BMI-adjusted leptin concentrations were not significantly associated with IMT (Pc (partial correlation): 0.41 in men and 0.15 in women). Moreover, when BMI was entered into a multiple linear regression model without leptin, the correlation between BMI and IMT was maintained in both men (P<0.005) and women (P<0.01), independent of the same parameters. CONCLUSION: Plasma leptin concentrations are independently associated with the IMT of the CCA, suggesting that the increase of adipose tissue mass (or leptin per se) may have an unfavourable influence on the development of atherosclerosis. However, the association between IMT and leptin seems to be dependent and/or confounded by the relationship between IMT and obesity.     

Dissociation between albuminuria and insulinaemia in hypertensive and atherosclerotic men

To better understand the links between circulating insulin and albuminuria in essential hypertension, the plasma insulin response t alpha a 75 gram glucose load and albuminuria were evaluated in 53 glucose-tolerant essential hypertensives and 12 controls. To allow any direct pressure-independent albuminuric effect of insulin to emerge more clearly, those same parameters were also evaluated in 20 glucose-tolerant normotensive patients with stable atherosclerotic peripheral vascular disease, a condition in which hyperinsulinaemia could be anticipated on the basis of previous reports. In response to glucose ingestion, hyperinsulinaemia was evident in both hypertensive and normotensive atherosclerotic patients, while, on average, urine albumin was elevated only in the former. When plasma insulin, systolic and diastolic blood pressure (BP) (by 24-h ambulatory BP monitoring), plasma glucose, triglycerides and body mass index were entered into a multiple regression analysis, only systolic BP appeared to exert an independent effect on urine albumin. Post-glucose load plasma insulin did not differ between hypertensive patients with (n = 14) and without (n = 39) microalbuminuria (albuminuria > 20 micrograms/min). In further analyses, insulin and systolic BP values were divided in quartiles: albuminuria did not differ across insulin quartiles, while it was significantly higher in the top (n = 21) vs the bottom (n = 21) systolic BP quartile. Thus, hyperinsulinaemia and microalbuminuria were unrelated variables in these hypertensive and atherosclerotic patients. Blood pressure, particularly systolic, emerged as a primary predictor of urinary albumin excretion, although the importance of this parameter needs to be proved prospectively.     

Blood pressure independent association of microalbuminuria and left ventricular hypertrophy in hypertensive men

BACKGROUND: Rather unique amongst the prognostic predictors, microalbuminuria (MA, albuminuria: 15-200 microg min-1) is associated with several cardiovascular risk factors including left ventricular hypertrophy (LVH). The relationship, usually assumed to reflect an increased blood pressure (BP) load on the heart and the kidney, may, however, represent more than a haemodynamic correlate. METHODS: To evaluate this possibility, we related MA to left ventricular mass index (LVMI) and other functional and structural echocardiographic parameters, office and 24-h BP, weight, lipids and smoking status in 330 never treated nondiabetic hypertensive men. RESULTS: The risk of MA increased linearly by ascending quartiles of LVMI and was 2.3-fold higher in the presence of LVH after adjustment for age, left atrial size, mean fractional shortening. Systolic BP, either office or 24 h, and smoking status were the only additional independent predictors in multivariate logistic regression models. The BP-adjusted risk of MA was about twofold higher in patients with LVH, either concentric or eccentric, and neutral in those with concentric remodelling compared with normal geometry. CONCLUSIONS: The association between elevated LVMI and MA independent of several other potential confounders, systolic BP in particular, is consistent with the existence of cardiac albuminuric factors, possibly of hormonal nature, which are to be identified more precisely. The extent to which LVH explains the predictive power of MA for morbid events independent of the BP load remains unknown.     

Relationship between carotid artery intima-media thickness and brachial artery flow-mediated dilation in middle-aged healthy men

OBJECTIVES: We aimed to determine the relationship between carotid intima-media thickness (IMT) and brachial artery flow-mediated dilation (FMD) in healthy middle-age men. BACKGROUND: Carotid IMT and brachial artery FMD are frequently used as surrogate measures of subclinical atherosclerosis. Whereas carotid IMT identifies early structural abnormalities, brachial artery FMD, considered a bioassay of endothelial function, measures functional vascular integrity. The relationship between carotid IMT and brachial artery FMD has not been well studied. METHODS: We measured traditional risk factors, carotid IMT, and brachial artery FMD in 1,578 middle-aged men without known cardiovascular disease and analyzed the relationship between carotid IMT and brachial FMD. RESULTS: Carotid IMT correlated with age, systolic blood pressure, body mass index, fasting glucose, total and low-density lipoprotein (LDL) cholesterol, and with the overall Framingham risk score (p < 0.001 for all), whereas impaired brachial artery FMD correlated with systolic and diastolic blood pressure (p < 0.01). No relationship was observed between carotid IMT and brachial artery FMD for the entire cohort (r = -0.006, p = 0.82) and in subgroups defined by traditional risk factors or by quintiles of carotid IMT and brachial FMD. CONCLUSIONS: In middle-aged healthy men, there is no significant correlation between carotid IMT and brachial artery FMD. This finding suggests that these are unique, independent surrogates that measure different aspects and stages of early atherosclerosis. Further studies are needed to define their role in clinical research and in cardiovascular risk assessment.     

Prehypertension is associated with atherosclerosis in Type 2 diabetes

Background: Prehypertension is a risk factor for hypertension, diabetes, and cardiovascular diseases. However, the association between prehypertension and atherosclerosis in Type 2 diabetes mellitus (T2DM) has not been evaluated. In the present study, we investigated the impact of prehypertension on atherosclerosis in T2DM. Methods: Patients (n = 930) with T2DM were recruited for the present study from the outpatient clinic of Shanghai Ruijin Hospital. The intima–media thickness (IMT) of the common carotid artery (CCA) was determined using ultrasound and brachial–ankle pulse wave velocity (baPWV) was determined by volume plethysmography to assess atherosclerosis. Results: Of the 930 patients with T2DM (mean age of 59 years), 167 were categorized as normotensive, 213 were prehypertensive, and 550 were hypertensive. Diabetic subjects with prehypertension had significantly higher CCA‐IMT and baPWV than those with normal blood pressure after adjustment for age and gender. Multiple logistic regression analysis revealed that, compared with normotension, prehypertension was a significant independent determinant of atherosclerosis (for maximum IMT ≥1.1 mm, odds ratio (OR) 2.10 and 95% confidence interval (CI) 1.28–3.44; for baPWV ≥1400 cm/s, OR 3.09 and 95% CI 1.78–5.36). Conclusion: Prehypertension is associated with atherosclerosis independent of conventional cardiovascular risk factors in T2DM patients. We speculate that maintenance of systolic blood pressure <120 mmHg and diastolic blood pressure <80 mmHg may reduce the risk of atherosclerosis in T2DM.     

Cholesterol and triglyceride concentrations in lipoproteins as related to carotid intima-media thickness

Since distinct cholesterol and triglyceride concentrations in major lipoproteins and their subclasses may be related to atherosclerosis, we investigated the relationship of cholesterol and triglyceride concentrations in lipoprotein subclasses and the severity of carotid intima-media thickness (IMT), a surrogate marker of subclinical atherosclerosis. We studied 116 apparently healthy Japanese men (53 ± 9 years) without a history of cardiovascular diseases who were not taking any medication. Carotid IMT was measured by means of high-resolution vascular ultrasound. Plasma cholesterol and triglyceride concentrations in major lipoproteins and their subclasses were determined by HPLC with gel permeation columns. By univariate analyses, carotid IMT was the most closely related to age (r = 0.528, P < 0.001), followed by smoking habit expressed as pack-year cigarette consumption (r = 0.409, P < 0.001). In addition to total cholesterol and LDL cholesterol, carotid IMT was significantly associated with cholesterol and triglyceride concentrations in several LDL and VLDL subclasses. Stepwise multiple linear regression analysis revealed that age (β = 0.436, P < 0.001), smoking (pack-years) (β = 0.225, P = 0.007), and large LDL cholesterol (β = 0.175, P = 0.023) were independent predictors of determining carotid IMT (adjusted R(2) = 0.347, P < 0.001). These results indicate that large LDL cholesterol is an important, independent determinant of carotid IMT in healthy men.     

Increased augmentation of central blood pressure is associated with increases in carotid intima–media thickness in type 2 diabetic patients

Aims/hypothesis Type 2 diabetes is associated with a two- to seven-fold increase in cardiovascular morbidity and mortality. The aim of this study was to determine the relationships between intima–media thickness (IMT), an established marker of atherosclerosis, large artery function and other determinants of cardiovascular risk in type 2 diabetic patients.Methods We studied 228 type 2 diabetic patients (75 women, aged 62±2 years [mean±SEM]). Carotid IMT was bilaterally measured using ultrasound technology. Applanation tonometry and pulse wave analysis were used to measure aortic systolic and diastolic blood pressures, central pressure augmentation (AG) and the augmentation index (AIx), a measure of systemic arterial stiffness. Conventional cardiovascular risk factors (lipids, HbA₁c, smoking and diabetes duration) were also assessed.Results Women had higher AG and AIx (p<0.0001), despite comparable systolic BP and heart rate in women and men. In women, AG (r=0.39, p<0.001), age (r=0.32, p<0.01), brachial systolic BP (r=0.34, p<0.01) and aortic systolic BP (r=0.34, p<0.01) correlated with IMT. In men, age (r=0.41, p<0.001), diabetes duration (r=0.25, p<0.01), AG (r=0.22, p<0.01), aortic systolic BP (r=0.21, p<0.01), brachial systolic BP (r=0.21, p<0.01) and body weight (r=0.16, p<0.05) correlated with IMT. In multiple linear regression analyses, AG and aortic systolic BP, but not brachial systolic BP, were age-independent determinants of IMT in men and women. In all patients, increased AG (adjusted for sex, age and heart rate) correlated with longer duration of diabetes, urinary albumin excretion and IMT.Conclusions/interpretation Measures of central systolic pressure correlate with carotid IMT, independently of age and other risk markers.     

颈动脉超声对动脉粥样硬化性疾病的研究进展

颈动脉超声是一种安全、有效、非侵入性评价临床及亚临床动脉粥样硬化的一种检测手段。大量研究证实颈动脉内膜 中膜厚度 (IMT)与冠状动脉粥样硬化的出现密切相关 ,而且IMT增厚是冠心病事件、脑卒中和短暂性脑缺血的独立危险因素。有经验实验室精细的颈动脉超声检查及IMT测值能作为动脉粥样硬化性疾病特别是心血管病事件的替代指标。     

Hypertensive smokers have a worse cardiovascular risk profile than non-smokers in spite of treatment--a national study in Sweden

Smoking is a well-established risk factor for cardiovascular disease. Studies have indicated that smoking may outweigh the benefit of blood pressure (BP) control. Our aim was to compare cardiovascular risk factors in smokers vs non-smokers from a national sample of treated hypertensives. Data were collected on smoking habits, BP control, total and low-density lipoprotein (LDL) cholesterol, diabetes, left ventricular hypertrophy (LVH), and microalbuminuria (MA), from records of 4424 consecutive patients by 189 physicians. All technical methods were local. Treated hypertensives who smoked had microalbuminuria significantly more often than non-smokers, 26.2% vs 20.5% (p<0.05), and a higher proportion of smokers were suboptimally controlled (DBP > or = 90 mmHg), 32.7% vs 25.0% (p<0.01). Smoking males had a higher prevalence of LVH (25.7% vs 20.1; p<0.05), microalbuminuria (29.7% vs 24.7%; p<0.01), and a higher proportion of subjects with uncontrolled systolic BP (> or = 140 mmHg) (72.8% vs 68.9%; p<0.01). Both DBP and total cholesterol were higher in smoking vs non-smoking females. An increased prevalence of LVH and microalbuminuria was independently associated with smoking. In summary, smokers with treated hypertension show a higher proportion of LVH (men), microalbuminuria and worse diastolic BP control than non-smokers. This may hypothetically reflect either less compliance with drug treatment in smokers or that smoking impairs the pharmacological effects of antihypertensive drugs.     

Age and sex differences in the relationship between inherited and lifestyle risk factors and subclinical carotid atherosclerosis: the Tromsø study

BACKGROUND: Ultrasound measurement of carotid artery intima-media thickness (IMT) is regarded as a valid index of atherosclerosis. Age and sex differences in the distribution of, and risk factors for, IMT have not been investigated thoroughly. METHODS: In 1994-1995 a total of 6408 men and women aged 25-84 years living in the municipality of Troms?, Norway, underwent ultrasound examination of carotid artery IMT and measurements of cardiovascular risk factors. RESULTS: Age, systolic blood pressure, total cholesterol, HDL cholesterol, body mass index, and smoking were independent predictors of IMT in both sexes. Fibrinogen levels and physical activity were associated with IMT in men only, whereas triglyceride levels were associated with IMT independently of HDL cholesterol in women only. A family history of cardiovascular disease (CVD) was an independent predictor of IMT in both sexes, also when controlling for traditional CVD risk factors. The magnitude of the association between most risk factors and IMT did not differ depending on age, but the effects of physical activity and triglycerides were more pronounced at higher age. CONCLUSION: These data suggest that there are significant age and sex differences in the distribution and the determinants of subclinical atherosclerosis.     

Increased human urotensin II levels are correlated with carotid atherosclerosis in essential hypertension

BACKGROUND: Circulating blood levels of human urotensin II (U-II), the most potent vasoconstrictor peptide identified to date, are increased in patients with essential hypertension. Our previous studies showed that U-II accelerates human macrophage foam cell formation and vascular smooth muscle cell proliferation, suggesting development of atherosclerotic plaque. In this study, we demonstrated a correlation between plasma U-II level and progression of atherosclerosis in hypertensive patients. METHODS: The intima-media thickness (IMT) and plaque score in the carotid artery, blood pressure (BP), plasma levels of U-II, and atherosclerotic parameters were determined in 50 hypertensive patients and 31 normotensive controls. RESULTS: Plasma U-II level, maximum IMT, plaque score, systolic BP, and homeostasis model assessment for insulin resistance (HOMA-IR) were significantly greater in hypertensive patients than normotensive controls. Age, gender, body mass index, and serum levels of high-sensitive C-reactive protein (CRP), HDL and LDL cholesterols, small dense LDL, triglycerides, lipoprotein(a), insulin, and fasting plasma glucose level were not significantly different between the two groups. In all subjects, plasma U-II level showed significant positive correlations with systolic BP, maximum IMT, plaque score, and HOMA-IR. Multiple logistic regression analysis indicated that the contribution of plasma U-II levels to carotid plaque formation (plaque score >/=1.1) was significantly still greater with a 60% increase than those of established risk factors, such as age, systolic BP, high-sensitive CRP, small dense LDL, and HOMA-IR. CONCLUSIONS: Our results suggest that increased levels of U-II may play a crucial role in the development of carotid atherosclerosis in hypertensive patients.     

Cardiovascular risk profile of asymptomatic healthy young adults with increased femoral artery intima-media thickness: The Bogalusa Heart Study

BACKGROUND: Femoral artery intima-media thickness (IMT), like carotid IMT, is a surrogate indicator of atherosclerotic coronary and peripheral vascular diseases in middle-aged and older adults. This study examined the cardiovascular disease risk profile of asymptomatic young adults with increased femoral artery IMT. METHODS: Femoral artery IMT was measured by B-mode ultrasonography in 1080 black and white subjects (aged 24-43 years; 71% white, 43% male) enrolled in the Bogalusa Heart Study. Individuals in the top (n=54) versus bottom fifth (n=54) percentiles distribution of femoral IMT were compared for traditional cardiovascular risk factors profile. Univariate analysis compared the two groups, t-tests and chi tests were performed. RESULTS: The top and bottom fifth percentiles of IMT differed with respect to age (P<0.001), systolic blood pressure (P<0.05), diastolic blood pressure (P<0.05), total cholesterol (P<0.01), low-density lipoprotein (LDL) cholesterol (P<0.001), non-high-density lipoprotein (HDL) cholesterol (P<0.01) and smoking status (P<0.01). In terms of prevalence of clinically defined traditional risk factors, individuals at the top versus bottom fifth percentile of IMT distribution had significantly higher prevalence of high LDL cholesterol (>OR=130 mg/dL), non-HDL cholesterol (>OR=160 mg/dL), and cigarette smoking. The odds ratio for individuals with three or more risk factors versus no risk factors having IMT in the top fifth percentile was 4.7 (P=0.01). CONCLUSION: The observed adverse effect of cardiovascular risk factors on IMT of femoral artery, a surrogate measure of coronary and peripheral atherosclerosis, in asymptomatic young individuals underscores the need for risk factors profiling in early life. These observations have important implications in preventive medicine.     

Microalbuminuria is an integrated marker of subclinical organ damage in primary hypertension

Increased urine albumin excretion is associated with an unfavourable cardiovascular risk profile and prognosis in primary hypertension, even though its pathogenesis is currently unknown. Microalbuminuria (Mi) has been proposed as an integrated marker to identify patients with subclinical organ damage, but its routine use is still too often neglected in clinical practice. The aim of our study was to evaluate the relationship between urinary albumin excretion and early signs of subclinical target organ damage (TOD), namely left ventricular hypertrophy and carotid atherosclerosis in a large group of non diabetic hypertensive patients. A group of 346 never treated patients with primary hypertension (212 men, 134 women, mean age 47 +/- 9 years) referred to our clinic were included in the study. They underwent the following procedures: (1) family and personal medical history and physical examination; (2) clinical blood pressure measurement; (3) routine blood chemistry and urine analysis including determination of urinary albumin excretion (ACR); (4) electrocardiogram; (5) ultrasound evaluation of left ventricular mass (LVMI) and carotid artery thickness (IMT). The overall prevalence of Mi, left ventricular hypertrophy, and carotid plaque was 13, 51, and 24% respectively. Mi was significantly correlated with LVMI (P < 0.0001), IMT (P < 0.0001) and several metabolic and non-metabolic risk factors (blood pressure, body mass index, serum lipids). Cluster analysis identified three subgroups of patients who differ significantly with regards to TOD and albuminuria (P < or = 0.001 for each of the examined variables). Patients with higher IMT and LVMI values also showed increased ACR levels. Furthermore, patients with microalbuminuria were more likely to have both LVH and IMT values above the median for the study population (OR 21, C.I. 4.6-99.97, P < 0.0001). Mi is an integrated marker of subclinical organ damage in patients with primary hypertension. Evaluation of urinary albumin excretion is a specific, cost-effective way to identify patients at higher risk for whom additional preventive and therapeutic measures are advisable.     

Microalbuminuria,a parameter independent of metabolic influences in hypertensive men

OBJECTIVE: To evaluate the relationship of albuminuria and microalbuminuria (overnight urine albumin > or = 15 micro g/min) with insulin resistance and related metabolic abnormalities in patients with essential hypertension. DESIGN: Cross-sectional evaluation of 271 (age range, 19-77 years) never-treated, non-diabetic, uncomplicated hypertensive men. MAIN OUTCOME MEASURES: Triplicate overnight urine albumin determination and homeostasis model assessment (HOMA) of insulin resistance as a surrogate measure of insulin sensitivity. Additional parameters were fasting and post-load circulating glucose and insulin, lipids, body mass index, blood pressure and echocardiographic left ventricular mass. RESULTS: HOMA, fasting and post-challenge glucose and insulin, percentages of glucose-intolerant patients, triglycerides and high-density lipoprotein cholesterol levels did not differ across ascending urine albumin quartiles. Body mass index, blood pressure and ventricular mass were significantly greater in the upper quartiles, and the prevalence of obesity fivefold more frequent in the top as compared with the bottom urine albumin fourth. The statistical trend was unchanged after adjustment for HOMA, while accounting for systolic blood pressure and left ventricular mass by co-variance analysis abolished it. Eighty-eight patients bearing the phenotypic traits of the metabolic syndrome and a striking degree of insulin resistance and hyperinsulinemia showed urine albumin rates and prevalence of microalbuminuria comparable with the 183 patients who were not affected by that syndrome. CONCLUSIONS: Albuminuria is independent of insulin resistance and other phenotypic components of the metabolic syndrome in never-treated, non-diabetic essential hypertensive men. Microalbuminuria is more frequent in obese hypertensives but this association is explained by higher blood pressure more than insulin resistance.     

Carotid atherosclerosis,intima media thickness and risk factors--an analysis of 1781 asymptomatic subjects in Taiwan

The aim of this study was to investigate the association of intima media thickness (IMT) and plaque with risk factors for atherosclerosis in asymptomatic subjects in Taiwan. Between 1998 and 2001, the study recruited 1781 asymptomatic subjects (1131 men and 650 women [mean age, 49 years; range 18-85 years]). These were examined by B-mode ultrasound to measure the IMT at the far wall of the common carotid artery (CCA) and the extent of plaque formation. A wide range of vascular risk factors including age, gender, smoking, body mass index, blood chemistry, and previous history were surveyed. The mean (+/-S.D.) IMT observed was 0.68 (+/-0.12) and 0.66 (+/-0.11) mm for men and women, respectively, (P=0.0008). The mean (S.D.) IMT of the CCA was 0.66 (+/-0.12) mm on the right side and 0.68 (+/-0.12) mm on the left side (P=0.0004). IMT increased with aging, according to the equation IMT=(0.005xage in years)+0.403 [corrected]. Higher IMT was associated with male gender, and IMT was greater in the left CCA. About 36.9% of subjects had carotid plaques. The percentage of plaque increased with aging. The plaque prevalence was positively associated with IMT. The value of IMT over the cut point of 0.68 mm correlated with obviously increased risk of carotid atherosclerosis. Age, systolic blood pressure and fasting blood sugar were independent risk factors related to both carotid atherosclerosis and thick IMT.     

Hypothyroidism is not associated with increased carotid atherosclerosis when cardiovascular risk factors are accounted for in hyperlipidemic patients

Overt hypothyroidism is associated with an increased prevalence of cardiovascular heart disease (CHD). The role of subclinical hypothyroidism as risk factor for cardiovascular diseases is supported by recent meta-analysis. However it still remains to be established whether hypothyroidism favors atherosclerosis independently of its effects on cardiovascular risk factors, such as hypercholesterolemia or hypertension. To assess whether hypothyroidism might be a risk factor per se, we analyzed carotid lesions assessed by US examination in two large populations with similar risk factors and displaying hypo- or euthyroidism. We selected, among a population of patients referred for assessment of hyperlipidemia, 794 hypothyroid patients (TSH>4mU/L), and 1588 euthyroid patients matched for the main cardiovascular risk factors (age, gender, lipid levels, hypertension, diabetes, smoking habits and obesity). All the patients had evaluation of their arterial carotid plaques, and about half of them had measurement of carotid intima-media thickness (IMT). Our hypothyroid population included 90% of patients with normal FT4 levels (subclinical hypothyroidism). We found that neither prevalence nor severity of carotid plaques nor carotid IMT were significantly different between hypothyroid patients and controls. To assess whether thyroid hormones may predict carotid atherosclerosis, we performed multivariate regression analyses, and we showed that, in both populations of hypothyroid and euthyroid patients, neither the TSH values nor the FT4 concentrations were independent risk factors for carotid atherosclerosis. In conclusion, we showed that, among a population of hyperlipidemic patients, hypothyroidism is not associated with an increased risk for carotid atherosclerosis when cardiovascular risk factors are accounted for.