Helga Gudmundsdottir

Arterial plasma noradrenaline predicts left ventricular mass independently of blood pressure and body build in men who develop hypertension over 20 years

Background Increased sympathetic activity may be an underlying mechanism in cardiovascular disease. It has been hypothesized that the degree of left ventricular (LV) hypertrophy is partly related to the blood pressure level, and partly to neurohormonal factors. The aim of this study was to investigate predictors of LV mass, including arterial plasma noradrenaline as an index of sympathetic activity, with particular emphasis on subjects who developed hypertension over a period of 20 years. Methods In a 20-year prospective study of middle-aged men, sustained hypertensives (n = 22), new hypertensives (crossovers) (n = 17) and sustained normotensives (controls) (n = 17) were examined both at baseline and after 20 years of follow-up (at ages 42.1 ± 0.5 and 62.3 ± 0.6 years, respectively). Relationships between arterial plasma catecholamines, blood pressure and body mass index at baseline to left ventricular parameters by echocardiography at follow-up were investigated. Results Groups were homogeneous regarding age, gender, race and body build. The group of sustained hypertensives had significantly more LV hypertrophy (P = 0.025) and diastolic dysfunction (P = 0.010). Among the crossovers, LV mass index was positively correlated to arterial plasma noradrenaline (r = 0.50, P = 0.043) and body mass index (BMI) (r = 0.51, P = 0.039) and showed a positive trend with systolic blood pressure (SBP) at baseline. Arterial plasma noradrenaline (β = 0.47) was found to predict LV mass index after 20 years independently of BMI (β = 0.45) and SBP (β = 0.22) at baseline (R2 adjusted = 0.345, P = 0.037). Such a relationship was not found in the controls or in the sustained hypertensives, of which 16 were treated with antihypertensive drugs. Conclusions Arterial plasma noradrenaline at baseline, as an index of sympathetic activity, predicts LV mass at follow-up independently of systolic blood pressure and body build in middle-aged men who developed hypertension over a period of 20 years.

Hypertension in women: latest findings and clinical implications:

Cardiovascular disease claims more women’s lives than any other disease. Hypertension is an important risk factor for cardiovascular disease in women but is often underestimated and undiagnosed and there is an ongoing misperception that women are at a lower risk of cardiovascular disease than men. The attainment of clinical blood pressure goals can markedly reduce cardiovascular morbidity and mortality, yet approximately two-thirds of treated hypertensive women have uncontrolled blood pressure. Furthermore, there are special risk factors that are unique for women that needs acknowledgement in order to help prevent the great number of hypertension-related events in women. Guidelines for treatment of hypertension are similar for men and women. More studies on the interaction between gender and response to antihypertensive drugs would be of interest.

Treatment of isolated systolic hypertension in diabetes mellitus type 2

Age‐related arterial stiffness is more pronounced in diabetics compared to non‐diabetics, which could explain the prevalence of isolated systolic hypertension (ISH, systolic blood pressure ≥140 mmHg and diastolic blood pressure <90 mmHg) being approximately twice that of the general population without diabetes. Large‐scale interventional outcome trials have also shown that diabetics usually have higher pulse pressure and higher systolic blood pressure than non‐diabetics. Advanced glycation end‐product formation has been implicated in vascular and cardiac complications of diabetes including loss of arterial elasticity, suggesting possibilities for new therapeutic options. With increasing age, there is a shift to from diastolic to systolic blood pressure and pulse pressure as predictors of cardiovascular disease. This may affect drug treatment as different antihypertensive drugs may have differential effects on arterial stiffness that can be dissociated from their effects on blood pressure. While thiazide diuretics are associated with little or no change in arterial stiffness despite a robust antihypertensive effect, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers and calcium‐channel blockers have been shown to reduce arterial stiffness. However, combination therapy is nearly always necessary to obtain adequate blood pressure control in diabetics. There are no randomized controlled trials looking specifically at treatment of ISH in diabetics. Recommendations regarding treatment of ISH in diabetes mellitus type 2 are based on extrapolation from studies in non‐diabetics, post‐hoc analyses and prespecified subgroup analysis in large‐scale studies, and metaanalysis. These analyses have clearly demonstrated that blood pressure lowering in ISH confers improved prognosis and reduced cardiovascular and renal outcomes in both diabetics and non‐diabetics.

Controlling systolic blood pressure is difficult in patients with diabetic kidney disease exhibiting moderate-to-severe reductions in renal function.

This study compared the use of antihypertensive treatment and blood pressure (BP) controls between patients with diabetic kidney disease (DK+) and patients with non‐diabetic kidney disease (DK−) exhibiting moderate‐to‐severe chronic renal failure who did not need renal replacement therapy. A cross‐sectional survey included all renal patients with s‐creatinine at ⩾200 µmol/l attending regular control sessions at six renal units in Norway. Of the 351 patients included, 73 (20.8%) were DK+. The proportion reaching a BP goal of <130/80 mmHg was similar in DK+ and DK− (14.1% vs 13.6%, p = 0.92), while 38% and 39% achieved a BP of <140/90 mmHg, respectively. The systolic BP goal was more difficult to achieve than the diastolic BP goal in DK+ patients (35% vs 15%) despite a mean of three different types of drugs being used. Loop diuretics and beta‐adrenergic‐receptor antagonists were the most frequently prescribed drugs, and the use of angiotensin‐converting enzyme inhibitors or angiotensin‐II‐receptor antagonists declined when renal function deteriorated, from 80% to 0% and from 66% to 20% in the DK+ and DK− groups, respectively (p = 0.001). Thus, despite the use of multiple antihypertensive drugs, controlling BP – especially the systolic BP – is difficult in high‐risk patients with chronic renal failure caused by diabetic kidney disease.

Self-perceived quality of sleep and mortality in Norwegian dialysis patients

Sleep complaints are prevalent and associated with poor health‐related quality of life (HRQoL), depression and possibly mortality in dialysis patients. This study aimed to explore possible associations between sleep quality, daytime sleepiness and mortality in dialysis patients. In this study, 301 dialysis patients were followed up to 4.3 years. HRQoL was evaluated at baseline with the Kidney Disease and Quality of Life—Short Form (KDQoL‐SF), depression with Beck Depression Inventory (BDI), sleep quality with Pittsburgh Sleep Quality Index and daytime sleepiness with Epworth Sleepiness Scale. The single item “on a scale from 0–10, how would you evaluate your sleep?” in the sleep subscale in KDQoL‐SF was used to identify poor (0–5) and good sleepers (6–10). A total of 160 patients (53.3%) were characterized as poor sleepers. They were younger (r = 0.241, P < 0.001), had more depression (BDI: 8.72 ± 6.79 vs. 13.60 ± 8.04, P < 0.001), a higher consumption of hypnotics and antidepressants and reduced HRQoL (Mental Component Summary score: 45.4 ± 11.0 vs. 50.0 ± 10.4, P < 0.001. Physical Component Summary score: 35.0 ± 9.9 vs. 38.5 ± 10.5, P = 0.004). In multivariate analyses, poor sleepers had nearly a twofold increase in mortality risk (hazard ratio [HR] 1.92, confidence interval [CI] 1.10‐3.35, P = 0.022). Daytime sleepiness was not related to mortality (HR 1.01, CI 0.95‐1.08, P = 0.751). Sleep complaints predicted increased mortality risk in dialysis patients and should therefore be routinely assessed. Further studies are needed to find suitable treatment options for poor sleep in dialysis patients as it may affect both HRQoL and survival.

Varicella Infection in a Renal Transplant Recipient Associated with Abdominal Pain, Hepatitis, and Glomerulonephritis

A 36-year-old renal transplant patient developed 9 years after a successful transplantation a fatal secondary varicella infection. The disseminated varicella infection was associated with hepatitis with liver necrosis, disseminated intravascular coagulation and fibrinolysis and glomerulonephritis. To our knowledge this is the first description of glomerulonephritis associated with varicella infection in a renal transplanted patient. The autopsy showed morphologically a mesangial glomerulonephritis with minor proliferative activity and extensive deposits by electronmicroscopy, mainly in the mesangium. The ongoing immunosuppression may have modified the mesangial cell response to the deposition of immune complexes.A 36-year-old renal transplant patient developed 9 years after a successful transplantation a fatal secondary varicella infection. The disseminated varicella infection was associated with hepatitis with liver necrosis, disseminated intravascular coagulation and fibrinolysis and glomerulonephritis. To our knowledge this is the first description of glomerulonephritis associated with varicella infection in a renal transplanted patient. The autopsy showed morphologically a mesangial glomerulonephritis with minor proliferative activity and extensive deposits by electronmicroscopy, mainly in the mesangium. The ongoing immunosuppression may have modified the mesangial cell response to the deposition of immune complexes.

Blood pressure development and hypertensive retinopathy: 20-year follow-up of middle-aged normotensive and hypertensive men

Screening for hypertensive organ damage is important in assessing cardiovascular risk in hypertensive individuals. In a 20-year follow-up of normotensive and hypertensive men, signs of end-organ damage were examined, focusing on hypertensive retinopathy. In all, 56 of the original 79 men were reexamined for hypertensive organ damage, including by digital fundus photography. The diameters of the central retinal artery equivalent (CRAE) and vein were estimated and the artery-to-vein diameter ratio calculated. Components of metabolic syndrome were assessed. Fifty percent of the normotensive men developed hypertension during follow-up. Significant differences appeared in CRAE between the different blood pressure groups (P=0.025) while no differences were observed for other markers of hypertensive organ damage. There were significant relationships between CRAE and blood pressure at baseline (r=–0.466, P=0.001) and at follow-up (r=–0.508, P<0.001). A linear decrease in CRAE was observed with increasing number of components of the metabolic syndrome (β=–3.947, R2=0.105, P=0.023). Retinal vascular diameters were closely linked to blood pressures and risk factors of the metabolic syndrome. The diversity in the development of hypertensive organ damage, with changes in retinal microvasculature preceding other signs of damage, should encourage more liberal use of fundus photography in assessing cardiovascular risk in hypertensive individuals.

Clinical aspects of a nationwide epidemic of severe haemolytic uremic syndrome (HUS) in children.

BackgroundReport a nationwide epidemic of Shiga toxin-producing E. coli (STEC) O103:H25 causing hemolytic uremic syndrome (D+HUS) in children.MethodsDescription of clinical presentation, complications and outcome in a nationwide outbreak.ResultsTen children (median age 4.3 years) developed HUS during the outbreak. One of these was presumed to be a part of the outbreak without microbiological proof. Eight of the patients were oligoanuric and in need of dialysis. Median need for dialysis was 15 days; one girl did not regain renal function and received a kidney transplant. Four patients had seizures and/or reduced consciousness. Cerebral oedema and herniation caused the death of a 4-year-old boy. Two patients developed necrosis of colon with perforation and one of them developed non-autoimmune diabetes.ConclusionThis outbreak of STEC was characterized by a high incidence of HUS among the infected children, and many developed severe renal disease and extrarenal complications. A likely explanation is that the O103:H25 (eae and stx2 -positive) strain was highly pathogen, and we suggest that this serotype should be looked for in patients with HUS caused by STEC, especially in severe forms or outbreaks.

Do screening blood pressure and plasma catecholamines predict development of hypertension? Twenty‐year follow‐up of middle‐aged men

Objectives. The sympathetic nervous system is implicated in the development and maintenance of hypertension. However, the predictive impact of arterial plasma catecholamines has never been reported. We investigated arterial catecholamines and blood pressures (BPs) prospectively over 20 years in a group of well‐characterized middle‐aged men. Methods. Fifty‐six of original 79 men were available for the follow‐up. Multiple regression analysis was done with mean BP at follow‐up as a dependent variable, and arterial plasma catecholamines and BP at baseline as independent variables. Results. Half of the originally normotensive men developed hypertension during follow‐up. There were significant differences in the screening BP values measured at baseline between the new hypertensives and the sustained normotensives. Multiple regression analysis revealed arterial adrenaline at baseline as an independent predictor of mean BP at follow‐up in the new hypertensives (β = 0.646, R2 = 0.42, p = 0.007). Furthermore, arterial noradrenaline at baseline was a negative independent predictor of mean BP at follow‐up in the sustained normotensives (β = −0.578, R2 = 0.334, p = 0.020). Noradrenaline increased with age in the group as a whole (1318±373 vs 1534±505 pmol/l, p = 0.010) while adrenaline did not change. Conclusion. Our data suggest that arterial adrenaline is involved in the development of hypertension over 20 years in middle‐aged men. Men with sustained normotension may have an inherent protection against sympathetic overactivity. Furthermore, screening BP at baseline in normotensive men differentiated between those who developed hypertension and those who remained normotensive at follow‐up.

Increased hematocrit before blood pressure in men who develop hypertension over 20 years

We have previously demonstrated that neurohormonal activity can predict left ventricular (LV) mass in men who developed hypertension over 20 years. The aim of the study was to investigate early markers of cardiac and hemorheological changes at baseline in these men, i.e., before a rise in blood pressure. Fifty-six middle-aged men were followed for 20 years; 22 were sustained hypertensives, 17 developed hypertension, and 17 were sustained normotensives. They were compared at baseline (42 years) and follow-up (62 years). We investigated Cornell voltage product and Sokolow-Lyon voltage, hematocrit (Hct), and echocardiographic LV parameters. There was no sign of LV hypertrophy by electrocardiography (ECG) at baseline. Baseline Hct discriminated between the groups (P= .015) and correlated to diastolic blood pressure (DBP) at baseline (r = 0.37, P= .006) and follow-up (r = 0.31, P= .020). Regression analysis identified baseline Hct as an independent correlate of DBP in the cohort at baseline when they were untreated (beta = .33, P= .013, R(2) = 0.25), and of borderline significance at follow-up (beta = .26, P= .060, R(2) = 0.12) despite possible interference by antihypertensive drugs. Hct was elevated at baseline compatible with the hypothesis that pathogenic hemorheological processes could be activated at the outset and prior to cardiac changes in men who later develop hypertension.