Cardiovascular protection in patients with type 2 diabetes mellitus: Considerations about the tightness of blood pressure control and the choice of treatment.

Diabetes mellitus is rapidly evolving as the epidemic of the 21st century. The presently estimated number of 190 million is predicted to grow to over 300 million by the year 2025. Cardiovascular (CVD) morbidity and mortality is two to five times higher in diabetics, while the microvascular complications considerably compromise the quality of life. The main risk factors for CVD, as well as for microangiopathy, are hypertension, dyslipidemia, insulin resistance, hyperglycemia, endothelial dysfunction, and an inflammatory vascular reaction. This review will focus on hypertension, which develops in most patients within the first 10-15 years of their diabetes. The discussion will encompass the criteria for treatment, the target values of blood pressure, and the choice of antihypertensive drugs as primary agents and in various combinations. The special role of angiotensin-receptor blockers will be highlighted, with an emphasis on cardioprotection, risk reduction of stroke, and attenuation of the course of nephropathy.

Teaching and motivating patients to control their risk factors retards progression of cardiovascular as well as microvascular sequelae of Type 2 diabetes mellitus- a randomized prospective 8 years follow-up study.

AIMS: To examine whether motivating patients to gain expertise and closely follow their risk parameters will attenuate the course of microvascular and cardiovascular sequelae of diabetes. METHODS: A randomized prospective study on 165 patients with diabetes mellitus Type 2, hypertension (> 140/90 mmHg) and hyperlipidaemia (LDL-C > 3 mmol/l), referred for consultation to a diabetes clinic in an academic hospital. Patients were randomly allocated to standard consultation (SC) or to a patient participation (PP) and teaching programme. Follow-up continued by primary care physicians. RESULTS: The mean follow-up was 7.7 years. SC group patients each attended eight annual consultations. The PP patients initiated on average 1.2 +/- 0.8 additional consultations per annum. The relative risk (RR) over 8 years, for the combined cardiovascular event index in the intervention (PP) vs. the control (SC) group was 0.65 (95% CI 0.41-0.89, P = 0.001). Nephropathy developed in 14 vs. 7 patients in the SC and PP groups, respectively, RR 0.50 (95% CI 0.28-0.85, P = 0.02), retinopathy developed in 35 vs. 21 patients, RR 0.60 (95% CI 0.21-0.82, P = 0.03). Throughout the study, period blood pressure, LDL-C and HbA1c were significantly lower in the PP than in the SC patients. CONCLUSION: Well-informed and motivated patients, were more successful in maintaining good control of their risk factors, resulting in reduced cardiovascular risk and slower progression of microvascular disease.

The effect of spironolactone, cilazapril and their combination on albuminuria in patients with hypertension and diabetic nephropathy is independent of blood pressure reduction: a randomized controlled study.

OBJECTIVE: The effect of spironolactone, cilazapril and their combination on albuminuria was examined in a randomized prospective study in female patients with diabetes and hypertension. PATIENTS AND METHODS: Sixty female diabetic patients aged 45-70 years with blood pressure (BP) 140-180/90-110 mmHg, serum creatinine (sCr) < or = 160 micro mol/l, HbA(1c) < or = 10%, and albuminuria were treated by atenolol 12.5-75 mg/d and hydrochlorothiazide 6.25-25 mg/d. Titration-to-target helped to reach BP values < or = 135/85 mmHg in 46 patients after 12 weeks. These patients were randomized to spironolactone 100 mg/d or cilazapril 5 mg/d for 24 weeks. Then both groups received spironolactone 50 mg/d and cilazapril 2.5 mg/d for 24 weeks. BP was stabilized by tapering the dose of the initial agents. Urinary albumin/creatinine ratio (ACR), BP, K(+). sCr and HbA(1c) were assessed at baseline and at weeks 12, 16, 36 and 60. RESULTS: The average BP at week 12 was 128 +/- 4/81 +/- 3 mmHg and remained constant, in both groups, throughout the study. ACR declined on spironolactone from a median value (range) of 452 (124-1571) to 216 (64-875) mg/g (P = 0.001), and on cilazapril to 302 (90-975) mg/g (P = 0.001). The difference between spironolactone and cilazapril was significant (P = 0.002). Combined treatment resulted in a further modest decline in ACR. Serum creatinine was unaltered by spironolactone and rose slightly (121 to 126 micro mol/l, P = 0.02) on cilazapril. CONCLUSION: At the doses tested, spironolactone was superior to cilazapril in reducing albuminuria. Combined administration was more effective than either drug alone. These effects were independent of BP values. Hyperkalaemia was the main side-effect.

The effect of acarbose on insulin resistance in obese hypertensive subjects with normal glucose tolerance: a randomized controlled study.

AIM: Acarbose, a glucose oxidase inhibitor, delays the absorption of glucose thus reducing post-prandial blood glucose level, haemoglobin A1c (HbA1c) and insulin resistance in patients with diabetes mellitus and in subjects with impaired glucose tolerance. The effect of acarbose in subjects with normal glucose tolerance (NGT) has hitherto not been examined. The aim of the present study was to examine the effect of acarbose in obese hypertensive subjects with NGT. METHODS: A double-blinded, parallel group study was performed on 56 male subjects with hypertension, body mass index (BMI) 27-35 kg/m2, fasting blood glucose < or =6 mmol/l and a normal oral glucose tolerance test. Blood pressure, HbA1c, lipid profile and insulin resistance [homeostasis model assessment (HOMA) index] were determined initially and following 24 weeks of acarbose, 150 mg/day or placebo. The primary end point was the change in insulin resistance. Anti-hypertensive treatment and diet were kept constant during the study. RESULTS: Insulin resistance decreased in acarbose users but not on placebo. HOMA index declined from 5.36 +/- 1.7 to 4.10 +/- 1.6 (p=0.001) on acarbose, the corresponding values on placebo were 5.44 +/- 1.9 and 5.53 +/- 1.7. A decrease in serum triglyceride values (2.16 +/- 0.16 mmol/l to 1.76 +/- 0.15 mmol/l, p=0.02) took place on acarbose with no change on placebo. There was no change in BMI, low-density lipoprotein or high-density lipoprotein values in either group. Blood pressure declined equally in both the groups, probably due to better patient compliance. CONCLUSIONS: Acarbose may reduce insulin resistance and triglycerides also in obese hypertensive subjects with normal glucose tolerance.

Teaching patients to monitor their risk factors retards the progression of vascular complications in high-risk patients with Type 2 diabetes mellitus--a randomized prospective study.

AIMS: Intensive management of risk parameters in diabetic patients may retard the progression of both micro- and macrovascular complications. Intensified care requires expert staff and is expensive. The aim of the present study was to examine whether sharing the therapeutic responsibility with the patients will improve the outcome. METHODS: A randomized prospective study of 165 patients with diabetes mellitus Type 2, hypertension (> 140/90 mmHg) and hyperlipidaemia (LDL-C > 120 mg/dl). Patients were randomly allocated to standard annual consultation (SC) or to a patient participation programme (PP). The medical care for both groups was administered by primary care physicians, who were unaware of the nature of the intervention. RESULTS: At 4 years the mean blood pressure was 148/88 (+/- 6.1/1.7) mmHg in the SC patients vs. 142/84 (+/- 5.8/1.8) mmHg in the PP group (P = 0.02). The mean LDL-C was 124 +/- 8 and 114 +/- 6 mg/dl (P = 0.01) and the mean HbA1c was 8.9 +/- 1.2% and 8.2 +/- 1.5% (P = 0.04) in the SC and PP groups, respectively. The average annual fall in estimated glomerular filtration rate was 3.5 ml/min per year in the SC group vs. 2.25 in the PP group (P < 0.05). Albumin/creatinine ratio > 300 mg/g developed in four SC patients vs. none of the PP patients. There was a total of 36 cardiovascular events in the SC group vs. 23 in the PP group (P = 0.04). All patients in the PP group received ACE inhibitors (or AII blockers) and statins vs. 52% and 43%, respectively, in the SC group. Glucose-lowering regimens were similar. CONCLUSIONS: Well-informed and motivated patients were more insistent to reach and maintain target values of the main risk factors of diabetic complications. The differences between the PP and SC groups were of the same order of magnitude as those between intensive and standard care groups in other studies albeit with, comparatively, a very modest cost.

Considerations about the threshold value of microalbuminuria in patients with diabetes mellitus: lessons from an 8-year follow-up study of 599 patients.

OBJECTIVE: To examine the validity of the time honored threshold value for microalbuminuria of 30 mg/24 h, by analyzing an 8-year follow-up data of 599 patients with diabetes mellitus type 2, normal blood pressure and base-line albumin excretion rate (AER)

Effect of enalapril and nifedipine on orthostatic hypotension in older hypertensive patients.

OBJECTIVE: To compare the effect of enalapril with long-acting nifedipine on orthostatic hypotension in older patients. DESIGN: A prospective, double blinded, cross-over study. SETTING: The outpatient clinic of a university hospital. PARTICIPANTS: Thirty-nine patients aged 65 years or older with systolic blood pressure (SBP) of 140-190 mm Hg and diastolic blood pressure (DBP) of 90-110 mm Hg. INTERVENTION: Enalapril 5-20 mg od or nifedipine 30-90 mg od for 8 weeks, followed by 4 weeks washout and cross-over for a second 8-week period. MEASUREMENTS: Supine and standing 0-, 1-, and 5-minutes blood pressure was recorded before and at the end of each treatment period. RESULTS: At baseline, SBP was 158.8 +/- 8.7 mm Hg, and DBP was 97.1 +/- 5.9 mm Hg. There was a decline in SBP of 6.1 +/- 2.7 mm Hg and 8.4 +/- 4.1 mm Hg after 1 and 5 minutes of standing, respectively. Both agents caused a significant decline in supine blood pressure. Enalapril: supine SBP 158.8 +/- 8.7 to 143 +/- 7.3 mm Hg; supine DBP 97.1 +/- 5.9 to 85.1 +/- 5.1 mm Hg (P = .0001). The drop in SBP after standing for 5 minutes was only 2.4 +/- 1.6 mm Hg with no change in diastolic values. A > or = 10 mm Hg drop in SBP was observed in only three patients, and no patient experienced a decline of 20 mm Hg or more. Nifedipine: supine SBP: 160.3 +/- 9 to 145.3 +/- 8.1 mm Hg; supine DBP: 96.3 +/- 5.7 to 86.3 +/- 5.8 (P = .0001). Nifedipine induced an orthostatic decline in SBP values; there was an 8.7 +/- 4.8 mm Hg difference between supine and 5 minutes standing values (P = .0005) without change in diastolic values. An orthostatic decline in SBP of > or = 10 mm Hg occurred in 13 patients, and there was a drop of > or = 20 mm Hg in six patients. The cross-over of enalapril and nifedipine reproduced the hypotensive effect and reversed the postural effect. (P = .0002 nifedipine vs enalapril) CONCLUSIONS: Enalapril and nifedipine were equipotent in reducing supine blood pressure levels. Enalapril also reduced the number of orthostatic episodes significantly, whereas nifedipine aggravated this phenomenon.

Hepatic periportal tracking associated with severe acute pyelonephritis.

The computed tomographic appearance of hepatic perivascular halos has been described in a variety of disorders. We observed three cases with sepsis due to acute pyelonephritis who presented with anasarca and had identical computed tomographic features of periportal edema associated with ascites, pleural effusion, a thickened gallbladder wall, and a dilated inferior vena cava. None of the three patients had an underlying disease process that was previously described as an etiology for an altered hepatic lymphatic dynamics. Acute severe pyelonephritis should be included in the differential diagnosis of extrahepatic diseases that cause hepatic perivascular lucencies.

Oxidation of low-density lipoprotein in normotensive type 2 diabetic patients. Comparative effects of enalapril versus nifedipine: a randomized cross-over over study.

The role of lipoprotein oxidation in promoting atherosclerosis is gaining recognition as its spectrum of effects is being unveiled. Accelerated atherosclerosis is a major cause of morbidity and mortality in diabetic patients. Treatment with ACE inhibitors reduces oxidation of low-density lipoprotein (LDL-ox) in hypertensive subjects, however, their effect on LDL-ox in diabetic patients is yet obscure. To evaluate the effect of the ACE inhibitor enalapril and the calcium channel blocker nifedipine on LDL oxidation in normotensive type 2 diabetic patients. A randomized single blinded cross-over study was conducted on 24 nonobese, metabolically stable, normotensive patients with type 2 diabetes who were randomly allocated to receive either enalapril, 10 mg/day, or nifedipine, 30 mg/day, for 4 weeks followed by a 2-week washout period. They were then crossed over to a 4-week course with the alternate drug. The oxidation of LDL was evaluated by three methods: dialdehyde analysis using the thiobarbituric acid reactive substances assay with and without the addition of CuSO(4) as well as determination of conjugated dienes in the LDL lipid extract. The propensity of the serum to oxidize LDL was reduced by enalapril by 17-28% depending on the laboratory method used (P=0.0001). Treatment with nifedipine resulted in a rise in LDL-ox of 7-11% as compared to baseline (P<0.05). The difference between the effects of enalapril and nifedipine was statistically significant with all three laboratory methods used (P=0.0001). Both drugs were equally effective in reducing systolic and diastolic blood pressure without affecting HbA(1c) levels and lipid profile. The albumin excretion rate was significantly reduced during treatment with enalapril returning to baseline levels during the washout period and the nifedipine treatment course. Our findings suggest that oxidation of LDL is attenuated by ACE inhibition and augmented by some calcium channel blockers. This observation may contribute insight into the underlying mechanism of the therapeutic effects of ACE inhibition in diabetic patients.

Risk factors for nephropathy in type 2 diabetes mellitus.

The main risk factors for diabetic nephropathy are hypertension, hyperlipidemia, and hyperglycemia. Nephropathy heralds the downhill course of arteriosclerosis. Early and intensive blood pressure and glucose control will attenuate the course of nephropathy and significantly reduce cardiovascular events and stroke.

Lung metastasis invading the left atrium--CT diagnosis.

A case of metastatic colonic adenocarcinoma invading the left atrium is reported in a patient with clinical signs of cardiac tamponade. The intracavitary extension of the tumour was clearly demonstrated by contrast enhanced CT. As CT plays an important role in the evaluation of patients with intrathoracic masses, intravenous contrast medium is recommended in those cases with associated clinical symptoms of heart disease or pericardial effusion. Its use may establish the diagnosis of cardiac involvement.

Effect of an alpha-adrenergic blocker, and ACE inhibitor and hydrochlorothiazide on blood pressure and on renal function in type 2 diabetic patients with hypertension and albuminuria. A randomized cross-over study.

alpha-Adrenergic blockers are potential alternative antihypertensive agents for diabetic patients. Data on their relative efficacy and their effect on kidney function and albuminuria are very limited however. 76 patients with diabetes type 2, hypertension (>/=140/90 mm Hg) and albuminuria (>/=30 mg/24 h) were randomized into three groups to receive cilazapril (2.5-10 mg), doxazosin (2-8 mg) or both. Patients of the first and second groups received a single agent for 4 months, the agents were then crossed for an additional period of 4 months followed by the addition of hydrochlorothiazide (25 mg) for a third 4-month period. Blood pressure was monitored monthly, creatinine clearance and HbA1c were measured before and at the end of each treatment period. Patients of the third group received reduced doses of cilazapril and doxazosin for 4 months. Hydrochlorothiazide was then added for the subsequent 4 months. There was a significant decline in blood pressure values during the first period in all groups. Cilazapril: systolic blood pressure (SBP) 160 +/- 6 to 149 +/- 5 mm Hg; diastolic blood pressure (DBP): 101 +/- 3 to 94 +/- 3 mm Hg (p = 0.001). Albuminuria declined from 350 +/- 105 to 205 +/- 96 mg/24 h (p = 0.001), creatinine clearance (CrCl) was unchanged. Doxazosin: SBP: 160 +/- 7 to 151 +/- 6 mm Hg; DBP: 97 +/- 4 to 90 +/- 4 mm Hg (p = 0.001). Albuminuria 373 +/- 121 to 322 +/- 107 mg/24 h (p = 0.065) and CrCl 87 +/- 7 to 91 +/- 6 ml/min. The combination of both agents at half doses was equipotent or superior to either drug alone. Cross-over of cilazapril and doxazosin reproduced the hypotensive effect and reversed the antialbuminuric effect. The addition of hydrochlorothiazide resulted in a further decline of 6-14 mm Hg in SBP and 3-11 mm Hg in DPB.