Diabetes og kronisk nyresykdom.

Chronic kidney disease is one of the most serious complications of diabetes. One of the challenges in the follow-up of patients with diabetes is to discover signs of kidney disease. Recent research shows that several drugs have renal protective effects. In this clinical review article we present markers used in the follow-up of patients with diabetes and chronic kidney disease, and new treatment options.

Troponin T is a better predictor than creatine kinase-MB of long-term mortality after coronary artery bypass graft surgery.

BACKGROUND: Elevations of creatine kinase-MB (CK-MB) and cardiac troponin T (cTnT) have an uncertain long-term prognostic value after coronary artery bypass graft (CABG) surgery. We aimed to test the hypothesis that CK-MB and cTnT are predictors of long-term survival after CABG and to assess which of these 2 biomarkers is the better predictor. METHODS: A total of 1,350 consecutive patients undergoing isolated on-pump CABG had CK-MB and cTnT measured at 7, 20, and 44 hours, postoperatively. The end point was all-cause mortality, and during the median follow-up time of 6.1 years, 207 patients (15.3%) died. RESULTS: Both peak CK-MB and peak cTnT independently predicted long-term mortality (hazard ratio [HR] 1.003, 95% confidence interval [CI] 1.001-1.005, P = .007, and HR 1.31, 95% CI 1.17-1.46, P <.001, respectively) when analyzed in separate multivariate Cox models, adjusting for baseline demographic characteristics and perioperative risk factors. However, when analyzed simultaneously in the same Cox model, cTnT was a significant predictor (HR 1.31, 95% CI 1.13-1.51, P <.001), whereas CK-MB was not (P = .99). Similar results were found when the biomarkers were analyzed together in a Cox model adjusting for European System for Cardiac Operative Risk Evaluation. The differences in mortality between the biomarker groups were consistent also when analyzing strict quartiles of peak values of CK-MB and cTnT (P = .81 and P = .001, respectively). CONCLUSIONS: Both CK-MB and cTnT are predictors of mortality after CABG surgery; however, our data suggest that cTnT is a better predictor of long-term mortality after CABG surgery than CK-MB.

Impact of new-onset diabetes mellitus on development of atrial fibrillation and heart failure in high-risk hypertension (from the VALUE Trial).

Hypertension and diabetes mellitus (DM) are known risk factors for atrial fibrillation (AF). We investigated the influence of new-onset DM on developing AF in the VALUE trial population of high-risk hypertensive patients. Five thousand two hundred fifty patients of the 15,245 participants in the VALUE trial had DM at baseline and 1,298 of the initially nondiabetic patients developed DM during the average 4.2-year follow-up. The presence of AF was determined by central analyzed electrocardiograms at baseline and changes were assessed yearly. Patients without AF at baseline and with any AF by later electrocardiograms were defined as patients with new-onset AF. Patients with new-onset and baseline DM were compared with patients without DM by a Cox regression model with adjustment for prespecified covariates. Five hundred fifty-one patients developed new-onset AF during the trial. Patients with new-onset DM had a significantly higher event rate of new-onset AF with a hazard ratio of 1.49 (1.14 to 1.94, p = 0.0031) compared with patients without DM, and there was a trend toward more AF in patients with DM at baseline. Patients with new-onset DM had also more persistent AF (hazard ratio 1.87, 1.28 to 2.74, p = 0.0014). Patients with new-onset DM and AF had a hazard ratio of 3.56 for heart failure (2.86 to 4.44, p <0.0001) compared with patients with new-onset DM without AF. In conclusion, hypertensive patients who developed DM during the VALUE trial had more AF than did patients without DM, and this may explain some of their concomitant high risk of hospitalization for heart failure.

Decreased levels of asymmetric dimethylarginine during acute hyperinsulinemia.

Endothelial dysfunction is reflected by an impaired nitric oxide (NO)-mediated vasodilatation. Insulin resistance may be linked to endothelial dysfunction by several mechanisms, including disturbances in signaling pathways common to both insulin action and NO production. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, may contribute to endothelial dysfunction, and elevated ADMA levels have been associated with both insulin levels and the degree of insulin resistance. The direct link between insulin and ADMA, however, has not yet been established. In the present study, we aimed to investigate the effects of acute hyperinsulinemia on circulating ADMA and L-arginine levels and on forearm blood flow (FBF). Male volunteers, aged 21 to 24 years, with borderline hypertension were included in the study. The participants underwent a 90-minute hyperinsulinemic isoglycemic glucose clamp with insulin levels at the postprandial levels (n=20) or a saline infusion (control) (n=9). Fasting blood samples were drawn at baseline and after 90 minutes. Insulin infusion was accompanied by a reduction in ADMA (0.78 to 0.68 micromol/L, P<.01), which was significantly different (P=.001) from the increase seen in the saline control group (0.69 to 0.79 micromol/L, P<.05). The same profile was obtained for L-arginine with a significantly more pronounced decrease (P<.001) in the insulin clamp group (74 to 61 micromol/L, P<.001) than in the saline control group (59 to 57 micromol/L, P=.95). The FBF level and nitrate/nitrite (NOx) levels were not affected by any of the clamp procedures. Short-term administration of insulin was accompanied by a decrease in both ADMA and L-arginine levels, with no change in FBF, in our population of young men with borderline hypertension. The possible influence of insulin on ADMA levels in a chronic state of insulin resistance can, however, not be deduced from the present investigation.

The effect of antihypertensive agents on new-onset diabetes mellitus: time to amend the guidelines?

Recent large hypertension trials have shown great differences in incidence of new-onset diabetes mellitus among patients receiving different antihypertensive drug therapies. The incidence of diabetes is unchanged or increased by the use of thiazide diuretics and beta-adrenoceptor antagonists (beta-blockers) and unchanged or decreased by ACE inhibitors, calcium channel blockers (CCBs), and angiotensin II type 1 receptor antagonists (angiotensin receptor blockers). Recent results from ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial) showed superiority of the 'new' combination of CCBs and ACE inhibitors over the 'old' or 'conventional' combination of beta-blockers and diuretics. In this review, the results from some of the large hypertension trials are discussed, and the hypotheses on how different antihypertensive drug regimens can affect glucose homeostasis are considered. The question now is whether the results from these recent trials should affect the choice of antihypertensive treatment, particularly for special groups. However, the key goal is still to reduce BP, and this usually requires combinations of drugs.

Effects on plasma noradrenaline may explain some of the improved insulin sensitivity seen by AT-1 receptor blockade.

AIMS: We have previously found improved insulin sensitivity in hypertensives after additional treatment with angiotensin II-receptor blocker (ARB) compared with calcium-channel blocker (CCB) alone, despite similar blood pressure lowering effects. In this study, we compare the effect of these two principal different vasodilating agents on the autonomic nervous system in the same patients, and test whether potential differences in these variables might explain the difference seen in insulin sensitivity. METHODS: In a double-blind crossover study, 21 hypertensive patients were randomized to receive either 100 mg losartan (ARB) or 5 mg amlodipine (CCB) in addition to an open-labelled treatment of amlodipine 5 mg. The patients were treated for 8 weeks with either treatment regimens after a 4-week run-in and a 4-week washout period. Plasma catecholamines were measured using radioenzymatic technique and baroreflex sensitivity and heart rate variability was tested at rest and during 24-h ECG registration. RESULTS: Plasma noradrenaline was significantly lower after additional treatment with ARB compared with CCB alone (304+/-29 pg/ml vs 373+/-43 pg/ml, p = 0.022). Heart rate variability, baroreflex sensitivity or plasma adrenaline did not differ significantly between the two treatment regimens. CONCLUSION: The results may suggest that improvement of insulin sensitivity by ARB is related to decreased plasma noradrenaline and potential sympatholytic effects.

Cardiovascular protection for all individuals at high risk: evidence-based best practice.

Patients with cardiovascular risk factors are largely undertreated, for many reasons. Vulnerable individuals may not be aware of the risks they are facing or an individual's risk of cardiovascular disease may be underestimated, particularly among those at high risk. Furthermore, in individuals identified as being at high total cardiovascular risk, the full spectrum of therapeutic options may not be implemented or patients may not adhere to the treatment prescribed. We address these critical issues by summarizing the existing guidelines: our ultimate goal is to encourage the optimal management of individuals at high total cardiovascular risk according to evidence-based medicine, with the expectation that this will improve outcomes.

Complications of hypertension and the role of angiotensin receptor blockers in hypertension trials.

Hypertension is a high-prevalence disease that may affect several organs. In recent years, data have accumulated indicating that angiotensin II receptor blockers (ARBs) may have a supplementary effect beyond lowering blood pressure. The aim of this review is to evaluate the impact of ARBs on the most important complications of hypertension--heart, cerebrovascular and renal diseases, and metabolic complications--based on the findings from large clinical hypertension trials. The results may indicate that ARBs have a superior effect compared with placebo or other antihypertensive drugs in order to prevent left ventricular hypertrophy, atrial fibrillation, stroke, renal disease and diabetes mellitus, while there appears to be no blood pressure-independent superior effect of ARBs regarding prevention of myocardial infarction or heart failure.

Personality may influence reactivity to stress.

BACKGROUND: Possible mechanisms behind psychophysiological hyperreactivity may be located at a cognitive-emotional level. Several personality traits have been associated with increased cardiovascular reactivity. Subjects with white coat hypertension, which may constitute a kind of hyperreactivity, are found to suppress their emotions and adapt to the surroundings to a larger extent than controls.We hypothesized in this study that a) stress reactivity is related to personality, and that b) responses to cold pressor test (CPT) and mental stress test (MST) are associated with different personality traits. METHODS: 87 men were selected from the 1st, 50th and 99th percentile of a blood pressure screening. Cardiovascular and catecholamine responses to MST and CPT were recorded. Fifteen personality traits were assessed using the Karolinska Scale of Personality. Possible independent explanatory predictors for cardiovascular and catecholamine variables at baseline and during stress were analyzed in multiple linear regression analyses using a stepwise forward procedure. RESULTS: Multiple regression analyses showed that muscular tension (beta = 0.298, p = 0.004), irritability (beta = 0.282, p = 0.016), detachment (beta = 0.272, p = 0.017), psychasthenia (beta = 0.234, p = 0.031) and somatic anxiety (beta = 0.225, p = 0.046) were significant explanatory variables of reactivity to CPT. During MST, verbal aggression (beta = -0.252, 0.031) and detachment (beta = 0.253, p = 0.044) were significant predictors of norepinephrine and diastolic blood pressure response, respectively.Based on KSP-trait quartiles, delta (Delta) systolic (p = 0.025) and Delta diastolic blood pressure (p = 0.003) during MST were related to detachment score, with the highest reactivity in the 4th quartile, while Delta norepinephrine was significantly related to muscular tension (p = 0.033). Delta systolic and Delta diastolic blood pressure responses to CPT were dependent on detachment (p = 0.049 and p = 0.011, respectively) and psychasthenia (p = 0.020 and p = 0.015), while high verbal aggression was associated with lower reactivity measured by Delta norepinephrine (p = 0.037). CONCLUSION: The present study indicates that stress reactivity is clearly related to different personality traits, without any single trait being dominant over others. Furthermore, personality seems to have as much, or even more, importance of predicting responses to CPT than responses to MST.

N-terminal pro-B-type natriuretic peptide in risk stratification after acute myocardial infarction in patients on long-term beta-adrenergic receptor blocker therapy.

BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-proBNP) appears to be a strong risk marker of mortality in patients with acute coronary syndrome. However, little information is available on NT-proBNP as a predictor of long-term serious cardiovascular events beyond that of left ventricular ejection fraction in patients with acute myocardial infarction (AMI), most of them treated with an early invasive strategy and on a uniform optimal secondary preventive medication including long-term beta-adrenergic receptor blockade. OBJECTIVE: To assess the prognostic impact of plasma NT-proBNP in patients with AMI who received optimal medical treatment including long-term beta-adrenergic receptor blockade. METHODS: Plasma NT-proBNP was measured in 219 patients (age range 31-80 years) with AMI at baseline, and then followed for a median duration of 1.63 years. The first occurrences of a serious cardiovascular event including cardiac mortality, nonfatal MI, and congestive heart failure were registered. RESULTS: Ninety serious cardiovascular events occurred. Left ventricular ejection fraction and reperfusion therapy with thrombolysis or percutaneous coronary intervention were identified as confounders. When adjusting for these factors in multivariate analysis, NT-proBNP was a strong predictor of serious cardiovascular events in patients with a plasma NT-proBNP of >162.2 pmol/l and aged <60 years (p = 0.001). The incidence rate was related to increasing NT-proBNP (p = 0.0017). The risk of serious cardiovascular events was higher in patients with NT-proBNP levels in the highest quartile (> or =162.2 pmol/l) than in those with levels in the three lowest quartiles (rate ratio = 2.5, 95% confidence interval = 1.6-3.9, p = 0.0001). CONCLUSION: AMI patients with high plasma NT-proBNP seem to be at an increased risk of serious cardiovascular events, but only those < or =60 years of age.

A comparison of the two beta-blockers carvedilol and atenolol on left ventricular ejection fraction and clinical endpoints after myocardial infarction. a single-centre, randomized study of 232 patients.

BACKGROUND: beta-Blockers have been found to reduce mortality and morbidity in postmyocardial infarction patients. However, it is not fully understood whether all beta-blockers have similar favourable cardiovascular effects. The aim of this study was to compare the effects of carvedilol and atenolol on global and regional left ventricular ejection fraction (LVEF) and on predefined cardiovascular endpoints. METHODS: In a single-centre, randomized, open, endpoint-blinded, parallel group study, 232 patients with acute myocardial infarction were randomized to treatment with carvedilol or atenolol. LVEF was measured by gated blood pool scintigraphy during the first week and after 12 months. The treatment was given orally within 24 h. The mean dose was 36.2 and 72.1 mg in the carvedilol and atenolol groups, respectively. RESULTS: No significant difference was found between the two study groups in the mean global and regional LVEF. There tended to be fewer first serious cardiovascular events in the carvedilol compared with the atenolol group (RR = 0.83, 95% CI 0.56-1.23, p = 0.39). Cold hands and feet were observed less frequently in the carvedilol group (20 vs. 33%, p = 0.025). CONCLUSION: In patients following an acute myocardial infarction, no difference in either global or regional LVEF was observed between baseline and 12 months when treatment with carvedilol was compared with atenolol.