Increased left ventricular mass index and nocturnal systolic blood pressure in patients with Type 2 diabetes mellitus and microalbuminuria.

AIMS: To compare left ventricular mass (LVM) index and function in patients with Type 2 diabetes mellitus with and without microalbuminuria and to investigate the clinical determinants of left ventricular hypertrophy. METHODS: Echocardiography, electrocardiography and 24-h ambulatory blood pressure monitoring were performed in microalbuminuric (n = 29) and normoalbuminuric (n = 29) patients with Type 2 diabetes and no clinical evidence of heart disease. Groups were individually matched for age, sex and diabetes duration and smoking status. RESULTS: LVM index (62 (34-87) vs. 52 (33-89) g/m2.7, P = 0.04) and LVH prevalence, using two out of three definitions, were greater in patients with microalbuminuria (LVM/height2.7: 72 vs. 59%, P = 0.27, LVM/height: 66 vs. 38%, P = 0.04, LVM/body surface area: 59 vs. 31%, P = 0.03). Night-time systolic blood pressure (126 (99-163) vs. 120 (104-157) mmHg, P = 0.005) and the night/day systolic blood pressure ratio (0.92 (0.08) vs. 0.88 (0.06), P = 0.04) were higher in those with microalbuminuria. Systolic and diastolic function were similar in both groups. Linear regression analyses showed that body mass index (BMI) was significantly related to loge LVM index (R2 = 11.8%, P = 0.005) and a relationship with night/day systolic blood pressure was also suggested (R2 = 4.6%, P = 0.057). CONCLUSIONS: In patients with Type 2 diabetes, LVH is more common and severe in those with microalbuminuria. Its presence may be related to raised night/day systolic blood pressure ratio and is significantly related to BMI. The high prevalence of LVH strengthens the case for echocardiographic screening in Type 2 diabetes to identify high risk patients who might benefit from aggressive cardiovascular risk factor intervention.     

Lisinopril reduces albuminuria during exercise in low grade microalbuminuric type 1 diabetic patients: a double blind randomized study

BACKGROUND: Antihypertensive treatment is presently recommended in most type 1 diabetic patients with microalbuminuria. The long-term effect of angiotensin converting enzymes (ACE) inhibitor (ACE-i) treatment on exercise urinary albumin excretion (E-UAE) and exercise blood pressure (E-BP) in type 1 diabetic patients with low grade microalbuminuria is not well documented. In addition, the possible predictive effect of baseline E-UAE on the progression of overnight UAE remains to be clarified. DESIGN AND METHODS: In a randomized placebo controlled double blind study the effects of 2 years treatment with either lisinopril (20 mg o.d.) or placebo was evaluated in 21 normotensive type 1 diabetic patients with overnight UAE between 20 and 70 microg min-1. Determinations of E-UAE and E-BP were performed after exercise on an ergometercycle with a load of 70% of estimated maximal VO2 for 20 min. Patients in the placebo and lisinopril groups were similar with regard to age (35.8 +/- 11.3 vs. 29.3 +/- 8.6 years), duration of diabetes (19.4 +/- 8.2 vs. 16.8 +/- 5.3 years), and HbA1c (9.0 +/- 1.0 vs. 9.4 +/- 1.7%). RESULTS: At baseline, E-UAE was similar in the two groups (placebo: 150.1 x or divide 3.7, lisinopril: 96.8 x or divide 1.8 microg min-1 (geometric mean x or divide tolerance factor)). After 2 years treatment E-UAE had increased in the placebo group, whereas E-UAE was reduced in the lisinopril treated patients (placebo: 213.6 x or divide 6.9, lisinopril: 48.3 x or divide 3.1 microg min-1, P = 0.04). The relative increase in E-UAE (E-UAE/Pre-exercise UAE) was similar at baseline in both groups (3.7 x or divide 2.3 vs. 2.8 x or divide 2.0) but significantly higher in the placebo group after 2 years (4.4 x or divide 2.4 compared with 1.6 x or divide 1.7 in the lisinopril group, P < 0.01) These changes over two years in relative increase in E-UAE were significantly different (P = 0.03). Exercise blood pressure was similar in both groups at baseline and over 2 years increased in the placebo group (from 166.5 +/- 15.1-179.9 +/- 35.6 mmHg), in contrast to the lisinopril group where E-BP was slightly reduced (from 168.5 +/- 20.6-165.1 +/- 16.6 mmHg) but the difference in blood pressure over the 2 years did not reach statistical significance. Exercise urinary albumin excretion and E-BP were closely associated (correlation for year 2: r = 0.734, P < 0.001), and also changes over the 2 years in E-UAE and E-BP were positively correlated (r = 0.53, P = 0.01). At year 2, overnight UAE, pre-exercise UAE (pre-E-UAE), E-UAE and E-BP were all closely linked (r-values between 0.6 and 0.9, P-values < 0.01). In the prediction of changes in overnight UAE over 2 years, neither baseline E-UAE nor baseline E-BP conveyed explanatory information in comparison with baseline overnight UAE and HbA1c. CONCLUSIONS: In type 1 diabetic patients with low-grade microalbuminuria, 2 years of ACE-i treatment with lisinopril significantly reduced E-UAE. Strong correlations were found between E-UAE and E-BP and also changes over 2 years in these parameters were significantly associated.     

The Natural Course of Microalbuminuria in Insulin-dependent Diabetes: A 10-year Prospective Study

The purpose of this study was to describe the clinical course in patients followed right from the onset of microalbuminuria to the development of diabetic nephropathy. A 10-year prospective follow-up of 209 consecutive normotensive insulin-dependent diabetic patients with normal urinary albumin excretion (UAE <30 mg 24 h^?1), age 34 (18–50) years and duration of diabetes 17 (10–30) years was performed. Twenty-four-hour urinary albumin excretion was measured every 4 months, glycated haemoglobin and supine blood pressure was measured annually. Two-hundred (96%) patients completed 10 (range 5–10) years follow-up. Twenty-nine (15%) patients developed persistent microalbuminuria (UAE 30–300 mg 24 h^?1). Eight of these have progressed to nephropathy and one had died of diabetic nephropathy. Multiple stepwise logistic regression analysis demonstrated baseline urinary albumin excretion (p = 0.0016) and glycated haemoglobin (p = 0.0014) but not blood pressure as predictors of development of microalbuminuria within the following 10 years. The median annual increase in urinary albumin excretion was 27 (range 17–65)% in the 29 patients developing microalbuminuria. The median duration from onset of microalbuminuria to development of nephropathy was 7 years. The prevalence of patients receiving antihypertensive treatment (BP > 140/90 mmHg) increased from 10% at onset of microalbuminuria to 45% 4 years after onset of microalbuminuria. The prevalence of patients with proliferative retinopathy increased from 7% at onset of microalbuminuria to 28% 4 years after onset of microalbuminuria. The incidence of persistent microalbuminuria in normotensive insulin-dependent diabetic patients is 2% per year, and development of persistent microalbuminuria is a strong predictor of overt nephropathy. Development of hypertension is frequent in the early course of microalbuminuria and treatment modalities for normotensive patients with microalbuminuria are urgently needed.     

Regression of left ventricular hypertrophy with 1 year of antihypertensive treatment in type 1 diabetic patients with early nephropathy

M-mode echocardiograms were recorded in 22 Type 1 diabetic patients with microalbuminuria (n = 10) or early persistent proteinuria (n = 12). Eight (36%) had both an increased left ventricular mass (males greater than 131 g m-2; females greater than 100 g m-2) and a systolic blood pressure above the 75th centile of the normal blood pressure distribution. These eight patients were treated with antihypertensive drugs, predominantly enalapril, for 1 year. Echocardiograms were repeated after 3 and 12 months. Systolic blood pressure at recruitment was 155 +/- 14 (+/- SD) mmHg, and was significantly lower after 3 months (146 +/- 12 mmHg; p less than 0.05) and 12 months (139 +/- 8 mmHg; p less than 0.005). Diastolic blood pressure did not change significantly. Both intraventricular septal width and left ventricular posterior wall thickness fell progressively and were significantly lower after 12 months treatment (15.0 +/- 2.7 vs 13.0 +/- 2.6 mm, and 10.3 +/- 1.9 vs 8.8 +/- 1.3 mm; both p less than 0.05). Left ventricular mass index was 148 +/- 29 g m-2 at recruitment, but lower after 3 months (131 +/- 25 g m-2; p less than 0.05) and 12 months (132 +/- 26 g m-2; p less than 0.005) antihypertensive therapy.     

Effects of low-dose losartan treatment on persistent microalbuminuria in normotensive type 1 diabetic subjects.

To examine the effect of low-dose losartan, an angiotensin II antagonist, on persistent microalbuminuria in normotensive Type 1 diabetes mellitus, 16 subjects with Type 1 diabetes were randomly assigned to two 2-month treatment periods, with either losartan (25 mg/day) or enalapril (5 mg/day) in a single-blind cross-over design. Urinary albumin excretion (UAE), blood pressures, lipids, glycemia, HbA1C, serum potassium and creatinine clearance were measured before and after each treatment period. The UAEs were similarly reduced after both treatments. The median UAE decreased by 27.8%, from 162 (range 65-250) to 117 (34-190) mg/day (p<0.01) after enalapril, and decreased by 25%, from 160 (60-246) to 120 (36-184) mg/day (p<0.01) after losartan. The systolic and diastolic blood pressures also decreased significantly (p<0.05), whereas serum levels of potassium increased (p<0.01) after both treatments. The levels of serum HbA1c, mean fasting glucose, total cholesterol, triglycerides, LDL cholesterol, HDL cholesterol and creatinine clearances were not significantly (p>0.05 in all) changed by either the enalapril or losartan treatment. No significant differences were found between the effects of enalapril and losartan. In conclusion, losartan treatment reduces microalbuminuria as effectively as enalapril in normotensive Type 1 diabetic patients.     

Autonomic nerve function in adolescents with Type 1 diabetes mellitus: relationship to microalbuminuria.

AIMS: Thirty adolescent patients with Type 1 diabetes mellitus and microalbuminuria were studied for evidence of early autonomic neuropathy. METHODS: Using tests involving cardiovascular and pupillary reflexes, the adolescents were compared with a normoalbuminuric group of patients with diabetes, who were matched for age, sex, puberty and duration of diabetes. RESULTS: There was an increased prevalence of autonomic nerve dysfunction in the patients with microalbuminuria. These patients had higher resting heart rates (86 beats/min in the microalbuminuric group vs. 77 beats/min in normoalbuminuric controls, P = 0.002), and impaired pupillary dilatation in darkness (pupillary diameter % 56.5% vs. 62.5%, P = 0.003). Patients with microalbuminuria also had poorer long term glycaemic control (mean HbA1C 8.7% vs. 7.8%, P = 0.002) and higher blood pressures (systolic 125 vs. 116 mmHg, P = 0.001; diastolic 69 vs. 62 mmHg, P = 0.0001; mean arterial pressure 90 vs. 83 mmHg, P = 0.002) than those with normal urinary albumin excretion. CONCLUSIONS: Microalbuminuria and autonomic nerve dysfunction co-exist in patients with Type 1 DM. Longitudinal studies will determine whether these findings have implications for the identification of patients at higher risk of progression of early renal complications.     

Microalbuminuria is associated with unfavourable cardiac geometric adaptations in essential hypertensive subjects

We sought in this study to examine the relationship between microalbuminuria and cardiac geometry since a slight increased urinary albumin excretion (UAE) and increased left ventricular (LV) mass have both been identified as predictors of cardiovascular events in hypertensive subjects. For this purpose, microalbuminuria was determined in three non-consecutive 24-h urine samples as UAE of 20-200 mg/24 h in a group of 249 untreated hypertensive subjects. Echocardiographic classification of patients into LV geometric patterns was based on relative wall thickness values and on gender-specific values for LV mass index (LVMI). The group of patients with microalbuminuria (n = 119) was matched for age, sex, body mass index, smoking status and plasma cholesterol level with the group of patients without microalbuminuria (n = 130). Subjects with microalbuminuria had significantly increased LVMI (111 vs 90 g/m(2), P < 0.0001), relative wall thickness (0.46 vs 0.41, P < 0.001) and office systolic and diastolic blood pressure (161 vs 148 and 101 vs 97 mmHg, respectively, P < 0.005). For the pooled population, UAE was positively correlated to LVMI (r = 0.46, P < 0.001) and relative wall thickness (r = 0.47, P < 0.001). In the entire population, normal LV geometry, concentric LV remodelling, eccentric and concentric LV hypertrophy was found in 34%, 33%, 12% and 21%, respectively. The prevalence of normal LV geometry was significantly higher in normoalbuminuric compared with microalbumnuric subjects (55 vs 14%, P < 0.001) while the prevalence of concentric LV hypertrophy was significantly higher in microalbuminuric compared with normoalbuminuric subjects (32 vs 5%, P < 0.0001). Multiple regression analysis revealed that concentric LV hypertrophy was significantly associated with increased values of UAE and mean arterial pressure. In conclusion, the higher prevalence of unfavourable LV geometric patterns in hypertensive subjects with microalbuminuria compared with those without microalbuminura, may account for the worse cardiovascular outcomes associated with the presence of an increased UAE in hypertensive subjects.     

Effect of pre-existing hypertension on the prevalence and incidence of microalbuminuria in non insulin-dependent diabetic patients

Microalbuminuria predicts increased rate of hypertension and mortality in insulino-dependent diabetics. In non insulin-dependent diabetes, hypertension often exists before onset of diabetes. To study effects of preexisting hypertension on prevalence and occurrence of elevated urinary albumin excretion (UAE), we collected datas from 614 non insulin-dependent diabetics, in a cross sectional survey: age was 60 +/- 10.4 years, (range 40-75 years), body mass index (BMI) 29 +/- 5.8 kg/m2, hemoglobin A1C 8 +/- 1.9%, systolic blood pressure (SBP) 134 +/- 18 mmHg, diastolic blood pressure (DBP) 76 +/- 10 mmHg, and serum creatinine 91 +/- 44 mumol/l. In the whole group, prevalence of hypertension was 59%. Microalbuminuria (EUA 20-200 mg/l) was present in 25.9% of the cases, microalbuminuria (EUA greater than 200 mg/l) in 7.5%. Cases with hypertension existing before or at onset of diabetes were 243 (HT group), cases without hypertension at onset were 371 (non HT group). In HT group, prevalence of microalbuminuria in increasing class of duration of diabetes were: 31% (0-4 years), 25% (5-9 years), 35% (10-14 years), 21% (15-19 years). Prevalence of macroalbuminuria was respectively: 3%, 11%, 15% and 4%. In the non HT group, microalbuminuria was present in 14% of the cases (0-4 years), 24% (5-9 years), 30% (10-14 years), 25% (15-19 years); prevalences of macroalbuminuria were: 1%, 8%, 6%, 15%. Mean values of UAE, compared to values of the class 0-2 years, were significantly higher in class 12-14 years (32.3 +/- 8 vs 14.4 +/- 3.7 mg/l; p = 0.02] in the HT group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Perinatal risk factors for early onset of Type 1 diabetes in a 2000–2005 birth cohort

Aims To examine perinatal risk factors for the onset of Type 1 diabetes before 6 years of age, in a 2000–2005 Australian birth cohort. Methods Data from longitudinally linked delivery and hospital admission records (until June 2007) were analysed. Diabetes in mothers and children was identified from International Classification of Diseases 10 diagnosis codes in the hospital records. Results There were 272 children admitted to hospital with a first diagnosis of diabetes out of 502 040 live births. Incidence for the infants born in 2000 was 16.0 per 100 000 person‐years. Maternal Type 1 diabetes was a significant risk factor [crude relative risk (RR) 6.33], but maternal Type 2 diabetes and gestational diabetes were not significantly associated with diabetes in the child. Late preterm birth (34–36 weeks) (RR 1.64) and caesarean section (RR 1.30) increased the risk of a diabetes admission. Size‐for‐gestational‐age was significantly associated with onset of diabetes (small‐for‐gestational age RR 0.48), but neither birth weight categories nor birth weight as a continuous variable were associated with risk of diabetes. Increasing maternal age was associated with an increased risk of diabetes in the child (RR 1.13 for each additional 5 years of age). Conclusions This study identified risk factors associated with onset of Type 1 diabetes before 6 years of age, in a recent birth cohort. Size‐for‐gestational‐age had a consistent association with risk of early onset of Type 1 diabetes, small size being protective. Size‐for‐gestational‐age measures should be preferred to birth weight thresholds when assessing risk of diabetes.     

Effects of lisinopril and nitrendipine on urinary albumin excretion and renal function in patients with mild to moderate essential hypertension.

The present study was designed to evaluate the effects of an ACE inhibitor, lisinopril, and a calcium antagonist, nitrendipine, on urinary albumin excretion (UAE) and renal function in mild to moderate essential hypertensive patients with microalbuminuria. After the 4-week drug-free period, 17 patients were randomly divided into two groups. The first group (group 1: n=8) received lisinopril 10-20 mg daily for 8 weeks followed by nitrendipine 5-10 mg daily for another 8 weeks. The second group (group 2: n=9) received nitrendipine 5-10 mg daily for 8 weeks followed by lisinopril 10-20 mg daily for another 8 weeks. The mean blood pressure (MBP) significantly decreased in a similar manner in both groups. UAE significantly decreased after 8 weeks of treatment with lisinopril in group 1 and after 8 weeks of subsequent treatment with lisinopril in group 2. On the other hand, UAE was not altered by treatment with nitrendipine. The changes in UAE were significantly correlated with changes in MBP after 8 weeks of treatment with nitrendipine, but not after 8 weeks of treatment with lisinopril. No significant changes in creatinine clearance, urinary excretion of sodium or urinary N-acetyl-beta-D-glucosaminide were observed by any treatment in either group. These results suggest that lisinopril, not nitrendipine, reduces UAE in essential hypertensive patients with microalbuminuria independently of its effective antihypertensive properties.     

Blood pressure by 24 h ambulatory recordings in type 2 (non-insulin dependent) diabetics. Relationship to urinary albumin excretion

The relationship between blood pressure and microalbuminuria, both associated with cardiovascular disease and death, is sparsely studied in Type 2 (non-insulin-dependent) diabetes, and results may be interfered by the phenomenon of "white-coat-hypertension". We therefore investigated blood pressure by 24h ambulatory recordings (oscillometry) and examined whether blood pressure related to the level of urinary albumin excretion rate (UAER) by synchronous 24h collections. Seventeen diabetics (50-75 years of age) with microalbuminuria (15 less than UAER less than 200 micrograms/min) (DM), 15 with normal urinary albumin excretion (DN) and 10 healthy controls (C) participated. All groups were of comparable sex, age degree of obesity and had normal serum creatinine, and the groups of diabetics were of similar known duration, glycemic control and frequency of antihypertensive treatment. Blood pressures measured at the clinic were significantly higher (p less than 0.01) than 24h recordings. An average systolic pressure of 142 +/- 11 mmHg in DN was increased (p less than 0.01) as compared to C: 130 +/- 10 mmHg, but no further increase was seen in DM: 146 +/- 19 mmHg. Diastolic pressures were not different among the groups (C: 77 +/- 8 mmHg, DN: 80 +/- 11 mmHg, DM: 79 +/- 9 mmHg). Average 24h systolic pressure correlated to the UAER r = 0.61, p = 0.009 in DM, whereas not in DN. By the present method we found isolated systolic hypertension in Type 2 diabetes which may express "vascular stiffness". There was, however, no further rise in blood pressure in patients with microalbuminuria, but in these patients albuminuria may be pressure dependent and/or expressive of vascular pathology.     

Predictors of the development of microalbuminuria in patients with Type 1 diabetes mellitus: a seven-year prospective study

Aims To determine risk factors for the development of persistent microalbuminuria (albumin excretion rate (AER) ≥ 30 μg/min) in Type 1 diabetes mellitus. Methods One hundred and forty-eight initially normotensive Type 1 diabetic patients with normal albumin excretion (< 30 μg/min) were followed prospectively in hospital diabetes outpatient clinics for a median of 7 years. Main outcome measures were: progression to persistent microalbuminuria (albumin excretion rate ≥ 30 μg/min on at least two consecutive occasions); rate of change of albumin excretion rate; development of arterial hypertension (systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 95 mmHg or commencement of antihypertensive therapy). Results In a median follow-up period of 7 years (range 6 months to 8 years), 14 patients progressed to persistent microalbuminuria, a cumulative incidence of 11% (95% confidence interval 6.36–16.94). AER remained persistently < 30 μg/min in 109 subjects and 25 developed intermittent microalbuminuria. In those who developed persistent microalbuminuria, baseline AER (16.2 (13.9–19.1) vs. 5.2 (3.8–9.2) μg/min, P < 0.01), blood pressure (136 (123–148)/80 (74–85) vs. 121 (118–124)/72 (70–73) mmHg, P < 0.05), and HbA₁ (10.2 (9.1–11.4) vs. 9.0 (8.7–9.4)%, P < 0.05) were higher than in those who continued to have persistent normoalbuminuria, retinopathy was more severe and height (1.64 (1.57–1.71) vs. 1.70 (1.69–1.72) m, P < 0.05) less. In multivariate analysis, baseline AER was the strongest predictor of the development of persistent microalbuminuria (P < 0.0001), followed by mean arterial pressure (P = 0.02) and HbA₁ (P = 0.05). Conclusions The level of AER, raised blood pressure and poor glycaemic control are the most important predictors of the development of microalbuminuria in Type 1 diabetes.     

Successful cardiovascular risk reduction in Type 2 diabetes by nurse-led care using an open clinical algorithm.

AIM: To implement a protocol-driven, nurse-led cardiovascular risk reduction clinic using an open clinical algorithm. The primary aim of the clinic was to optimize blood pressure (BP) control; secondary aims were to reduce modifiable cardiovascular risk factors. METHODS: We studied 110 people with Type 2 diabetes attending a diabetes out-patient centre at University Hospital Aintree, Liverpool. Patients taking one or more antihypertensive drugs were selected for referral to the nurse-led clinic if BP was > 140/85 mmHg; there was no age threshold. An open clinical algorithm was designed to direct the nurse on the use of antihypertensive, statin and aspirin therapy plus lifestyle advice and concordance. RESULTS: Thirty-one percent of patients attending for a first visit to the nurse-led clinic had BP within target when measured to British Hypertension Society standards out of the consultant clinic. Mean BP was 150/76 mmHg compared with 178/88 mmHg (P < 0.001). Subsequently, BP was reduced to 130/68 mmHg (P < 0.001), this reduction being sustained at review 9 months later (mean BP 133/67 mmHg), with 87 (79%) achieving BP 相似文献   

The angiotensin II receptor antagonist telmisartan reduces urinary albumin excretion in patients with isolated systolic hypertension: results of a randomized, double-blind, placebo-controlled trial

OBJECTIVE: To examine the effect of telmisartan or hydrochlorothiazide on the control of urinary albumin excretion (UAE) in patients with isolated systolic hypertension (ISH) unselected for albuminuria in a pre-planned substudy of a large, multicentre, double-blind, placebo-controlled, randomized study. METHODS: The Angiotensin II Receptor Antagonist Micardis in Isolated Systolic hypertension (ARAMIS) study compared the antihypertensive efficacy after 6 weeks of once-daily fixed doses of telmisartan 20, 40 or 80 mg versus hydrochlorothiazide 12.5 mg or placebo in patients (n = 1039, aged 35-84 years) with ISH (seated blood pressure 150-179/< 90 mmHg). The prospective substudy analysed UAE using spot morning samples. RESULTS: Urinary albumin (> 2.2-901.6 mg/l) was detected at baseline in 614 out of 918 patients who were included in the substudy analysis. In the telmisartan group (n = 354, all doses combined), a median reduction in UAE from a baseline of 14.1% [95% confidence interval (CI) 7.3, 21.8] was observed versus 1.1% (95% CI -13.5 to 16.0) and 2.7% (95% CI -0.9 to 19.9) in the hydrochlorothiazide (n = 140) and placebo (n = 120) groups, respectively. The difference between telmisartan and hydrochlorothiazide was significant (P = 0.017). Reductions in UAE with telmisartan were observed in patients with baseline normoalbuminuria, microalbuminuria or macroalbuminuria. Telmisartan and hydrochlorothiazide produced comparable reductions in systolic blood pressure in these patients. CONCLUSION: In patients with ISH unselected for baseline albuminuria, telmisartan 20-80 mg after 6 weeks' treatment afforded significantly greater lowering of UAE than hydrochlorothiazide 12.5 mg, irrespective of the baseline UAE, and despite comparable reductions in systolic blood pressure with both drugs.     

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.     

Is renoprotection by angiotensin receptor blocker dependent on blood pressure?: the Saitama Medical School, Albuminuria Reduction in Diabetics with Valsartan (STAR) study.

To explore the effects of various antihypertensive regimes on microalbuminuria, an angiotensin II receptor blocker (ARB), valsartan, was substituted for or added to treatment with a calcium channel blocker (CCB). After a 6-month CCB baseline period, 28 Japanese hypertensive patients with incipient diabetic nephropathy (defined as a urinary albumin excretion [UAE] of 30-300 mg/g creatinine), were assigned to two groups according to their blood pressure (BP) levels: in patients with a BP of more than 130/85 mmHg (n=17), valsartan was added to the CCB (Group A), while in patients with a BP <130/85 mmHg, valsartan alone was given (Group B: n=11) for 12 months. UAE was determined before and at 3, 6 and 12 months after the initiation of ARB. Although the initial BP was significantly higher in Group A (150/83 mmHg) than Group B (127/77 mmHg), BP was decreased to 141/78 mmHg in Group A and slightly, but not significantly, increased to 130/82 mmHg in Group B. In both groups, UAE was significantly decreased after ARB treatment (to 89% of the basal value in Group A and to 40.5% of the basal value in Group B) and did not differ each other and the amount of decrease did not differ significantly between the two groups. These results suggest that combination therapy with an ARB and CCB is very effective in lowering BP and UAE in cases in which BP is not well controlled, while, even in patients with a sufficient BP control of <130/85 mmHg, the use of ARB singly resulted in a significant decrease in UAE without a further decrease in BP, implying that the ARB had a renoprotective action independent of changes in BP.     

The impact of maternal HBsAg carrier status on pregnancy outcomes: a case-control study

BACKGROUND/AIMS: To examine the impact of maternal HBsAg carrier status on pregnancy outcomes. METHODS: Two hundred and fifty-three carriers of hepatitis B surface antigen (HBsAg) with singleton pregnancy, were retrospectively compared with 253 controls matched for age and parity and year of delivery. RESULTS: On univariable analysis, HBsAg carriers had higher incidences of threatened preterm labour at <37 weeks (11.9% vs. 6.3%, P=0.030), preterm birth at <34 weeks (4.7% vs. 1.2%, P=0.033), gestational diabetes mellitus (19.0% vs. 11.1%, P=0.012) and antepartum haemorrhage (11.5% vs. 5.5%, P=0.026). Their infants had lower Apgar scores at the 1st (8.47+/-1.67 vs. 8.87+/-1.07, P=0.001) and 5th minute (9.56+/-1.29 vs. 9.80+/-0.54, P=0.007), and increased incidence of intraventricular haemorrhage (4.7% vs. 0.8%, P=0.007). On multivariable analysis, the association between HBsAg carrier state with antepartum haemorrhage, gestational diabetes mellitus and threatened preterm labour were confirmed. CONCLUSIONS: HBsAg carriers have increased risk of gestational diabetes mellitus, antepartum haemorrhage, and threatened preterm labour. This may be related to the chronic inflammatory state in these subjects. The role of chronic HBV infection in pregnancy complications has to be further elucidated.     

Effects of Long-term Enalapril Treatment on Persistent Microalbuminuria in Normotensive Type 2 Diabetic Patients: Results of a 4-year,Prospective, Randomized Study

The beneficial effect of long-term treatment with an angiotensin-converting enzyme (ACE) inhibitor on urinary microalbumin excretion (UAE) and renal function was investigated in a 4 year, randomized prospective study in normotensive patients with non-insulin-dependent (Type 2) diabetes mellitus. Sixty-two normotensive patients with Type 2 diabetes mellitus and microalbuminuria but normal renal function were randomized to receive either enalapril 5 mg day⁻¹ or no treatment. In the enalapril-treated patients, UAE was reduced from 115.4 ± 80.1 to 95.6 ± 61.7 mg 24 h⁻¹ after 12 months (p<0.05) and to 75.3 ± 44.8 mg 24 h⁻¹ after 48 months (p<0.001). In the untreated group, UAE increased slowly from 93.9 ± 69.9 to 150.0 ± 144.5 mg 24 h⁻¹ after 48 months. No changes in creatinine clearance, blood pressure or HbA_1C were seen in either group during the 4-year period. In normotensive Type 2 diabetic patients with early stage of diabetic nephropathy, the ACE inhibitor enalapril may have a beneficial effect by decreasing microalbuminuria. This effect is long-lasting and probably independent of the antihypertensive action of the drug.     

Impact of renin-angiotensin system inhibition on microalbuminuria in type 2 diabetes: a post hoc analysis of the Shiga Microalbuminuria Reduction Trial (SMART)

The Shiga Microalbuminuria Reduction Trial (SMART) showed the advantage of ARB over CCB beyond the blood pressure (BP)-lowering effect in reducing microalbuminuria. To further assess the impact of BP control or renin-angiotensin system inhibition on microalbuminuria, the SMART patients were re-analyzed. Hypertensive patients with type 2 diabetes and microalbuminuria were randomly assigned to valsartan or amlodipine treatment groups for 24 weeks. Target blood pressure was set at <130/80 mmHg. Changes in the urinary albumin creatinine ratio (ACR) from baseline were assessed in the valsartan monotherapy (VM) group (n=33), the amlodipine monotherapy (AM) group (n=36), the concomitant valsartan and angiotensin-converting enzyme inhibitor group (VA) (n=33), and the concomitant amlodipine and angiotensin-converting enzyme inhibitor (AA) group (n=38). At the end of the study, mean BP was not different among the four treatment groups. The changes in ACR from baseline to the end of the treatment period in VM, AM, VA, and AA were -36%, +30%, -26%, and +8%, respectively. The dissociation between the anti-albuminuric and antihypertensive effects of valsartan or amlodipine was observed in the respective monotherapy groups. In the AA group, however, a significant positive relationship was found between the changes in ACR and those in systolic BP. In conclusion, RAS inhibitors may be necessary in order for calcium channel blockers to have an effect on microalbuminuria. Therefore, RAS inhibitors are first-line drugs for hypertensive patients with type 2 diabetes and microalbuminuria.     

Effect of chronic ACE inhibition on glucose tolerance and insulin sensitivity in hypertensive type 2 diabetic patients.

The question, of whether long-term treatment of essential hypertension with angiotensin-converting enzyme (ACE) inhibitors is capable of modifying glucose tolerance or insulin sensitivity in Type 2 (non-insulin dependent) diabetes, is still unsolved. We studied 14 moderately overweight Type 2 diabetic patients with essential hypertension in stable metabolic control after a run-in period and again after 3 months of antihypertensive treatment with the ACE inhibitor, captopril. Glucose tolerance was tested with a 75-g oral glucose load and insulin sensitivity was measured by the insulin suppression test, while dietary and drug treatment of the diabetes remained constant. In the whole group, mean blood pressure (MBP) fell progressively over 3 months from a baseline value of 123 +/- 3 mmHg to a final value of 115 +/- 2 mmHg (p < 0.005); in six patients, the change in MBP was < 5 mmHg (non-responders), thus giving a clinical response rate of approximately 60%. After treatment, fasting plasma glucose, insulin, free fatty acid (FFA), potassium, and glycated haemoglobin concentrations were unchanged from baseline. During the oral glucose tolerance test, the incremental glucose area-under-curve was 0.75 +/- 0.05 mol 120 min l-1 before and 0.76 +/- 0.06 mol 120 min l-1 after treatment (p = ns). Endogenous insulin response and suppression of plasma FFA levels were superimposable on the two occasions. During the insulin suppression test, steady-state plasma glucose levels were 14.4 +/- 1.3 vs 14.2 +/- 1.1 mmol l-1 before and after chronic ACE inhibition, respectively, at comparable hyperinsulinaemic plateaux (291 +/- 21 vs 287 +/- 14 pmol l-1).(ABSTRACT TRUNCATED AT 250 WORDS)