Differences in heart rate responses to upright posture are associated with variations in the high-frequency power of heart rate variability.

High resting heart rate is a cardiovascular risk factor, but limited data exist on the underlying hemodynamics and reproducibility of supine-to-upright increase in heart rate. We recorded noninvasive hemodynamics in 574 volunteers [age, 44.9 yr; body mass index (BMI), 26.4 kg/m2; 49% male] during passive head-up tilt (HUT) using whole body impedance cardiography and radial artery tonometry. Heart rate regulation was evaluated using heart rate variability (HRV) analyses. Comparisons were made between quartiles of supine-to-upright heart rate changes, in which heart rate at rest ranged 62.6-64.8 beats/min (P = 0.285). The average upright increases in heart rate in the quartiles 1-4 were 4.7, 9.9, 13.5, and 21.0 beats/min, respectively (P < 0.0001). No differences were observed in the low-frequency power of HRV, whether in the supine or upright position, or in the high-frequency power of HRV in the supine position. Upright high-frequency power of HRV was highest in quartile 1 with lowest upright heart rate and lowest in quartile 4 with highest upright heart rate. Mean systolic blood pressure before and during HUT (126 vs. 108 mmHg) and the increase in systemic vascular resistance during HUT (650 vs. 173 dyn·s/cm5/m2) were highest in quartile 1 and lowest in quartile 4. The increases in heart rate during HUT on three separate occasions several weeks apart were highly reproducible (r = 0.682) among 215 participants. To conclude, supine-to-upright increase in heart rate is a reproducible phenotype with underlying differences in the modulation of cardiac parasympathetic tone and systemic vascular resistance. As heart rate at rest influences prognosis, future research should elucidate the prognostic significance of these phenotypic differences.NEW & NOTEWORTHY Subjects with similar supine heart rates are characterized by variable increases in heart rate during upright posture. Individual heart rate increases in response to upright posture are highly reproducible as hemodynamic phenotypes and present underlying differences in the modulation of cardiac parasympathetic tone and systemic vascular resistance. These results indicate that resting heart rate obtained in the supine position alone is not an optimal means of classifying people into groups with differences in cardiovascular function.

Presence of gastrointestinal symptoms in IgA nephropathy: a cross-sectional study.

BACKGROUND: Gastrointestinal (GI) symptoms are common in end-stage kidney disease. Mounting evidence indicates that the intestine plays an important role in the pathogenesis of IgA nephropathy (IgAN). However, no studies have addressed the obvious question; do IgAN patients suffer from GI symptoms? METHODS: Presence of GI symptoms and health-related quality of life were evaluated using the validated Gastrointestinal Symptom Rating Scale (GSRS) and Psychological General Well-Being (PGWB) questionnaires in 104 patients with kidney biopsy-verified IgAN and in 147 healthy controls. A person was regarded to experience 'increased GI symptoms' if the GSRS score exceeded plus 1 standard deviation of the mean of the corresponding score in the healthy controls. RESULTS: According to the GSRS total score, the IgAN patients had more GI symptoms than the healthy controls (2.0 vs. 1.7, p < 0.001). Female IgAN patients had higher GSRS total score than male patients (2.2 vs. 1.7, p = 0.001). More IgAN patients with preserved kidney function (eGFR > 60ml/min/1.73m2) suffered from increased symptoms of diarrhoea (76 vs. 25%, p = 0.028), constipation (81 vs. 19%, p = 0.046) and reflux (85 vs. 15%, p = 0.004) than did IgAN patients with reduced kidney function (eGFR < 60ml/min/1.73m2). CONCLUSIONS: IgAN patients and especially female IgAN patients experienced more GI symptoms than healthy controls. More prevalent GI symptoms were already observed before kidney function was clearly reduced. Systematic enquiry of GI symptoms might increase the standard of care among IgAN patients. Moreover, GI symptoms may provide clues for future studies that examine the pathophysiology of IgAN.

Plasma uric acid is related to large arterial stiffness but not to other hemodynamic variables: a study in 606 normotensive and never-medicated hypertensive subjects.

BACKGROUND: Elevated level of plasma uric acid (PUA) has been associated with cardiovascular disease, but whether uric acid is an independent risk factor or merely a marker remains controversial. METHODS: We investigated in a cross-sectional setting the association of PUA with hemodynamics in 606 normotensive and never-medicated hypertensive subjects (295 men, 311 women, age range 19-73 years) without cardiovascular disease or gout. In all except 15 individuals, PUA was within the normal range. Supine hemodynamics were recorded using whole-body impedance cardiography and radial tonometric pulse wave analysis. RESULTS: The mean concentrations of PUA in age, sex and body mass index adjusted quartiles were 234, 278, 314, and 373 µmol/l, respectively. The highest PUA quartile presented with higher aortic to popliteal pulse wave velocity (PWV) than the lowest quartile (8.7 vs. 8.2 m/s, p = 0.026) in analyses additionally adjusted for plasma concentrations of C-reactive protein, low density lipoprotein cholesterol, triglycerides, and mean aortic blood pressure. No differences in radial and aortic blood pressure, wave reflections, heart rate, cardiac output, and systemic vascular resistance were observed between the quartiles. In linear regression analysis, PUA was an independent explanatory factor for PWV (ß = 0.168, p < 0.001, R2 of the model 0.591), but not for systolic or diastolic blood pressure. When the regression analysis was performed separately for men and women, PUA was an independent predictor of PWV in both sexes. CONCLUSIONS: PUA concentration was independently and directly associated with large arterial stiffness in individuals without cardiovascular disease and PUA levels predominantly within the normal range. Trial registration ClinicalTrials.gov NCT01742702.

Genome-wide association study of white-coat effect in hypertensive patients.

Background: White-coat effect (WCE) confounds diagnosis and treatment of hypertension. The prevalence of white-coat hypertension is higher in Europe and Asia compared to other continents suggesting that genetic factors could play a role. Methods: To study genetic variation affecting WCE, we conducted a two-stage genome-wide association study involving 1343 Finnish subjects. For the discovery stage, we used Genetics of Drug Responsiveness in Essential Hypertension (GENRES) cohort (n = 206), providing the mean WCE values from up to four separate office/ambulatory recordings conducted on placebo. Associations with p values <1 × 10-5 were included in the replication step in three independent cohorts: Haemodynamics in Primary and Secondary Hypertension (DYNAMIC) (n = 182), Finn-Home study (n = 773) and Dietary, Lifestyle and Genetic Determinants of Obesity and Metabolic Syndrome (DILGOM) (n = 182). Results: No single nucleotide polymorphisms reached genome-wide significance for association with either systolic or diastolic WCE. However, two loci provided suggestive evidence for association. A known coronary artery disease risk locus rs2292954 in SPG7 associated with systolic WCE (discovery p value = 2.2 × 10-6, replication p value = 0.03 in Finn-Home, meta-analysis p value 2.6 × 10-4), and rs10033652 in RASGEF1B with diastolic WCE (discovery p value = 4.9 × 10-6, replication p value = 0.04 in DILGOM, meta-analysis p value = 5.0 × 10-3). Conclusion: This study provides evidence for two novel candidate genes, SPG7 and RASGEF1B, associating with WCE. Our results need to be validated in even larger studies carried out in other populations.

Genome-wide association study of nocturnal blood pressure dipping in hypertensive patients.

BACKGROUND: Reduced nocturnal fall (non-dipping) of blood pressure (BP) is a predictor of cardiovascular target organ damage. No genome-wide association studies (GWAS) on BP dipping have been previously reported. METHODS: To study genetic variation affecting BP dipping, we conducted a GWAS in Genetics of Drug Responsiveness in Essential Hypertension (GENRES) cohort (n = 204) using the mean night-to-day BP ratio from up to four ambulatory BP recordings conducted on placebo. Associations with P < 1 × 10- 5 were further tested in two independent cohorts: Haemodynamics in Primary and Secondary Hypertension (DYNAMIC) (n = 183) and Dietary, Lifestyle and Genetic determinants of Obesity and Metabolic Syndrome (DILGOM) (n = 180). We also tested the genome-wide significant single nucleotide polymorphism (SNP) for association with left ventricular hypertrophy in GENRES. RESULTS: In GENRES GWAS, rs4905794 near BCL11B achieved genome-wide significance (ß = - 4.8%, P = 9.6 × 10- 9 for systolic and ß = - 4.3%, P = 2.2 × 10- 6 for diastolic night-to-day BP ratio). Seven additional SNPs in five loci had P values < 1 × 10- 5. The association of rs4905794 did not significantly replicate, even though in DYNAMIC the effect was in the same direction (ß = - 0.8%, P = 0.4 for systolic and ß = - 1.6%, P = 0.13 for diastolic night-to-day BP ratio). In GENRES, the associations remained significant even during administration of four different antihypertensive drugs. In separate analysis in GENRES, rs4905794 was associated with echocardiographic left ventricular mass (ß = - 7.6 g/m2, P = 0.02). CONCLUSIONS: rs4905794 near BCL11B showed evidence for association with nocturnal BP dipping. It also associated with left ventricular mass in GENRES. Combined with earlier data, our results provide support to the idea that BCL11B could play a role in cardiovascular pathophysiology.

Central wave reflection is associated with peripheral arterial resistance in addition to arterial stiffness in subjects without antihypertensive medication.

BACKGROUND: Augmentation index, a marker of central wave reflection, is influenced by age, sex, height, blood pressure, heart rate, and arterial stiffness. However, the detailed haemodynamic determinants of augmentation index, and their relations, remain uncertain. We examined the association of augmentation index with vascular resistance and other haemodynamic and non-haemodynamic factors. METHODS: Background information, laboratory values, and haemodynamics of 488 subjects (239 men, 249 women) without antihypertensive medication were obtained. Indices of central wave reflection, systemic vascular resistance, cardiac function, and pulse wave velocity were measured using continuous radial pulse wave analysis and whole-body impedance cardiography. RESULTS: In a regression model including only haemodynamic variables, augmentation index in males and female subjects, respectively, was associated with systemic vascular resistance (ß = 0.425, ß = 0.336), pulse wave velocity (ß = 0.409, ß = 0.400) (P < 0.001 for all), stroke volume (ß = 0.256, ß = 0.278) (P = 0.001 for both) and heart rate (ß = -0.150, ß = -0.156) (P = 0.049 and P = 0.036). When age, height, weight, smoking habits, and laboratory values were included in the regression model, the most significant explanatory variables for augmentation index in males and females, respectively, were age (ß = 0.577, ß = 0.557) and systemic vascular resistance (ß = 0.437, ß = 0.295) (P < 0.001 for all). In the final regression model, pulse wave velocity was not a significant explanatory variable for augmentation index, probably due to the high correlation of this variable with age (Spearman's correlation ≥0.617). CONCLUSION: Augmentation index is strongly associated with systemic vascular resistance in addition to arterial stiffness. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01742702 .

The type of the functional cardiovascular response to upright posture is associated with arterial stiffness: a cross-sectional study in 470 volunteers.

BACKGROUND: In a cross-sectional study we examined whether the haemodynamic response to upright posture could be divided into different functional phenotypes, and whether the observed phenotypes were associated with known determinants of cardiovascular risk. METHODS: Volunteers (n = 470) without medication with cardiovascular effects were examined using radial pulse wave analysis, whole-body impedance cardiography, and heart rate variability analysis. Based on the passive head-up tilt induced changes in systemic vascular resistance and cardiac output, the principal determinants of blood pressure, a cluster analysis was performed. RESULTS: The haemodynamic response could be clustered into 3 categories: upright increase in vascular resistance and decrease in cardiac output were greatest in the first (+45 % and -27 %, respectively), smallest in the second (+2 % and -2 %, respectively), and intermediate (+22 % and -13 %, respectively) in the third group. These groups were named as 'constrictor' (n = 109), 'sustainer' (n = 222), and 'intermediate' (n = 139) phenotypes, respectively. The sustainers were characterized by male predominance, higher body mass index, blood pressure, and also by higher pulse wave velocity, an index of large arterial stiffness, than the other groups (p < 0.01 for all). Heart rate variability analysis showed higher supine and upright low frequency/high frequency (LF/HF) ratio in the sustainers than constrictors, indicating increased sympathovagal balance. Upright LF/HF ratio was also higher in the sustainer than intermediate group. In multivariate analysis, independent explanatory factors for higher pulse wave velocity were the sustainer (p < 0.022) and intermediate phenotypes (p < 0.046), age (p < 0.001), body mass index (p < 0.001), and hypertension (p < 0.001). CONCLUSIONS: The response to upright posture could be clustered to 3 functional phenotypes. The sustainer phenotype, with smallest upright decrease in cardiac output and highest sympathovagal balance, was independently associated with increased large arterial stiffness. These results indicate an association of the functional haemodynamic phenotype with an acknowledged marker of cardiovascular risk. TRIAL REGISTRATION: ClinicalTrials.gov NCT01742702.

Effect of fermented milk product containing lactotripeptides and plant sterol esters on haemodynamics in subjects with the metabolic syndrome--a randomised, double-blind, placebo-controlled study.

We investigated the effects of fermented milk product containing isoleucine-proline-proline, valine-proline-proline and plant sterol esters (Pse) on plasma lipids, blood pressure (BP) and its determinants systemic vascular resistance and cardiac output. In a randomised, double-blind, placebo-controlled study, 104 subjects with the metabolic syndrome (MetS) were allocated to three groups in order to receive fermented milk product containing (1) 5 mg/d lactotripeptides (LTP) and 2 g/d plant sterols; (2) 25 mg/d LTP and 2 g/d plant sterols; (3) placebo for 12 weeks. Plasma lipids and home BP were monitored. Haemodynamics were examined in a laboratory using radial pulse wave analysis and whole-body impedance cardiography in the supine position and during orthostatic challenge. There were no differences between the effects of the two treatments and placebo on the measurements of BP at home or on BP, systemic vascular resistance index and cardiac index in the laboratory, neither in the supine nor in the upright position. The changes in plasma LDL-cholesterol concentration were - 0.1 (95% CI - 0.3, 0.1 and - 0.3, 0.0) mmol/l in the 5 and 25 mg/d LTP groups, respectively, and +0.1 (95% CI - 0.1, 0.3) mmol/l during placebo (P= 0.024). Both at baseline and at week 12, the increase in systemic vascular resistance during head-up tilt was lower in the 25 mg/d LTP group than in the 5 mg/d LTP group (P< 0.01), showing persistent differences in cardiovascular regulation between these groups. In subjects with the MetS, intake of LTP and Pse in fermented milk product showed a lipid-lowering effect of borderline significance, while no antihypertensive effect was observed at home or in the laboratory.

Association of resting heart rate with cardiovascular function: a cross-sectional study in 522 Finnish subjects.

BACKGROUND: High resting heart rate (HR) is associated with increased cardiovascular risk in general populations, possibly due to elevated blood pressure (BP) or sympathetic over-activity. We studied the association of resting HR with cardiovascular function, and examined whether the hemodynamics remained similar during passive head-up tilt. METHODS: Hemodynamics were recorded using whole-body impedance cardiography and continuous radial pulse wave analysis in 522 subjects (age 20-72 years, 261 males) without medication influencing HR or BP, or diagnosed diabetes, coronary artery, renal, peripheral arterial, or cerebrovascular disease. Correlations were calculated, and results analysed according to resting HR tertiles. RESULTS: Higher resting HR was associated with elevated systolic and diastolic BP, lower stroke volume but higher cardiac output and work, and lower systemic vascular resistance, both supine and upright (p < 0.05 for all). Subjects with higher HR also showed lower supine and upright aortic pulse pressure and augmentation index, and increased resting pulse wave velocity (p < 0.001). Upright stroke volume decreased less in subjects with highest resting HR (p < 0.05), and cardiac output decreased less in subjects with lowest resting HR (p < 0.009), but clear hemodynamic differences between the tertiles persisted both supine and upright. CONCLUSIONS: Supine and upright hemodynamic profile associated with higher resting HR is characterized by higher cardiac output and lower systemic vascular resistance. Higher resting HR was associated with reduced central wave reflection, in spite of elevated BP and arterial stiffness. The increased cardiac workload, higher BP and arterial stiffness, may explain why higher HR is associated with less favourable prognosis in populations.

High activity of indoleamine 2,3-dioxygenase is associated with renal insufficiency in Puumala hantavirus induced nephropathia epidemica.

Nephropathia epidemica (NE) is a hemorrhagic fever with renal syndrome caused by Puumala hantavirus. The severity of NE varies greatly. The aim of the present study was to evaluate whether serum indoleamine 2,3-dioxygenase (IDO) activity is associated with the severity of NE. A prospectively collected cohort of 102 consecutive patients with acute serologically confirmed NE was examined. Serum kynurenine, tryptophan, creatinine, CRP, and blood cell count were measured for up to 5 consecutive days after admission. The kynurenine to tryptophan (kyn/trp) ratio reflecting IDO activity was calculated. A maximum kyn/trp ratio >202 µmol/mmol had a sensitivity of 85% and a specificity of 75% for detecting maximum serum creatinine values >250 µmol/L by receiver operating characteristic (ROC) analysis. A maximum kyn/trp ratio >202 µmol/mmol (high IDO level) was also associated with other parameters reflecting the severity of the disease and renal impairment. Patients with high IDO levels had higher maximum serum creatinine (379 vs. 102 µmol/L, P<0.001), plasma C-reactive protein (104.1 vs. 72.1 mg/L, P=0.029), and blood leukocyte values (11.9 vs. 9.0 × 10(9) /L, P<0.001) compared to patients with kyn/trp ratio ≤ 202 µmol/mmol. They also had lower minimum urinary output (1,100 vs. 1,900 ml/day, P<0.001) and longer hospital stays (8 vs. 5 days, P<0.001). In conclusion, high serum IDO activity was associated with increased disease severity and renal impairment in NE.

The Clinical Presentation of Puumala Hantavirus Induced Hemorrhagic Fever with Renal Syndrome Is Related to Plasma Glucose Concentration.

Puumala hantavirus (PUUV) causes a hemorrhagic fever with renal syndrome characterized by thrombocytopenia, increased capillary leakage, and acute kidney injury (AKI). As glucosuria at hospital admission predicts the severity of PUUV infection, we explored how plasma glucose concentration associates with disease severity. Plasma glucose values were measured during hospital care in 185 patients with PUUV infection. They were divided into two groups according to maximum plasma glucose concentration: P-Gluc < 7.8 mmol/L (n = 134) and P-Gluc ≥ 7.8 mmol/L (n = 51). The determinants of disease severity were analyzed across groups. Patients with P-Gluc ≥7.8 mmol/L had higher hematocrit (0.46 vs. 0.43; p < 0.001) and lower plasma albumin concentration (24 vs. 29 g/L; p < 0.001) than patients with P-Gluc < 7.8 mmol/L. They presented with higher prevalence of pulmonary infiltrations and pleural effusion in chest radiograph, higher prevalence of shock and greater weight change during hospitalization. Patients with P-Gluc ≥ 7.8 mmol/L were characterized by lower platelet count (50 vs. 66 × 109/L; p = 0.001), more severe AKI (plasma creatinine 272 vs. 151 µmol/L; p = 0.001), and longer hospital treatment (8 vs. 6 days; p < 0.001) than patients with P-Gluc < 7.8 mmol/L. Plasma glucose level is associated with the severity of capillary leakage, thrombocytopenia, inflammation, and AKI in patients with acute PUUV infection.

Individual changes of central blood pressure in response to upright posture: different hemodynamic phenotypes.

OBJECTIVES: Most studies about upright regulation of blood pressure have focused on orthostatic hypotension despite the diverse hemodynamic changes induced by orthostatic challenge. We investigated the effect of passive head-up tilt on aortic blood pressure. METHODS: Noninvasive peripheral and central hemodynamics in 613 volunteers without cardiovascular morbidities or medications were examined using pulse wave analysis, whole-body impedance cardiography and heart rate variability analysis. RESULTS: In all participants, mean aortic SBP decreased by -4 (-5 to -3) mmHg [mean (95% confidence intervals)] and DBP increased by 6 (5--6) mmHg in response to upright posture. When divided into tertiles according to the supine-to-upright change in aortic SBP, two tertiles presented with a decrease [-15 (-14 to -16) and -4 (-3 to -4) mmHg, respectively] whereas one tertile presented with an increase [+7 (7-- 8) mmHg] in aortic SBP. There were no major differences in demographic characteristics between the tertiles. In regression analysis, the strongest explanatory factors for upright changes in aortic SBP were the supine values of, and upright changes in systemic vascular resistance and cardiac output, and supine aortic SBP. CONCLUSION: In participants without cardiovascular disease, the changes in central SBP during orthostatic challenge are not uniform. One-third presented with higher upright than supine aortic SBP with underlying differences in the regulation of systemic vascular resistance and cardiac output. These findings emphasize that resting blood pressure measurements give only limited information about the blood pressure status.

The severity of Puumala hantavirus induced nephropathia epidemica can be better evaluated using plasma interleukin-6 than C-reactive protein determinations.

BACKGROUND: Nephropathia epidemica (NE) is a Scandinavian type of hemorrhagic fever with renal syndrome caused by Puumala hantavirus. The clinical course of the disease varies greatly in severity. The aim of the present study was to evaluate whether plasma C-reactive protein (CRP) and interleukin (IL)-6 levels associate with the severity of NE. METHODS: A prospectively collected cohort of 118 consecutive hospital-treated patients with acute serologically confirmed NE was examined. Plasma IL-6, CRP, and creatinine, as well as blood cell count and daily urinary protein excretion were measured on three consecutive days after admission. Plasma IL-6 and CRP levels higher than the median were considered high. RESULTS: We found that high IL-6 associated with most variables reflecting the severity of the disease. When compared to patients with low IL-6, patients with high IL-6 had higher maximum blood leukocyte count (11.9 vs 9.0 x 10(9)/l, P = 0.001) and urinary protein excretion (2.51 vs 1.68 g/day, P = 0.017), as well as a lower minimum blood platelet count (55 vs 80 x 10(9)/l, P < 0.001), hematocrit (0.34 vs 0.38, P = 0.001), and urinary output (1040 vs 2180 ml/day, P < 0.001). They also stayed longer in hospital than patients with low IL-6 (8 vs 6 days, P < 0.001). In contrast, high CRP did not associate with severe disease. CONCLUSIONS: High plasma IL-6 concentrations associate with a clinically severe acute Puumala hantavirus infection, whereas high plasma CRP as such does not reflect the severity of the disease.

The severity of acute Puumala hantavirus infection does not predict the long-term outcome of patients.

BACKGROUND/AIMS: We have found greater urinary protein excretion and higher glomerular filtration rate (GFR) and blood pressure in patients 6 years after acute nephropathia epidemica (NE) compared with seronegative controls. The present aim was to establish whether the long-term outcome is determined by the severity of acute illness. METHODS: Serial plasma interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), creatinine, C-reactive protein, blood cell count as well as 24-hour urinary protein and overnight α(1)-microglobulin and albumin excretions were measured in 37 patients with acute NE. Human leucocyte antigen (HLA)-B, HLA-DRB1, TNF-α(-308) and IL-6(-174) alleles were also analyzed. After 6 years, GFR, blood pressure and urinary protein excretion were examined. RESULTS: There were no associations between the clinical severity of acute NE or the genetic factors determined and the increased GFR, hypertension or 24-hour urinary protein excretion observed 6 years later. The degree of inflammation during the acute phase was higher in patients who had increased urinary excretion of α(1)-microglobulin 6 years later compared with those with no α(1)-microglobulin excretion. CONCLUSION: Neither the severity of acute NE nor the host genetic factors determined the predicted renal function, blood pressure or 24-hour urinary protein excretion 6 years later.

Team-based "Get-a-Grip" lifestyle management programme in the treatment of obesity.

This study examined weight loss during an extensive 1-year lifestyle programme in primary care in Finland in overweight subjects (n = 134, age 18-69 years; BMI > 30, or BMI > 25 with a comorbidity that would benefit from weight loss) between 2009 and 2013 in a single arm design. The programme included four medical doctor visits, five sessions by a dietitian (advice on diet and on-location shopping behaviour), cooking classes, exercise supervised by personal trainer, and group discussions. A motivational interview method was applied. Of the 134 participants, 92 (69%) completed the 1-year programme. Among the participants 44% lost ≥ 5%, while 21% lost ≥ 10% of their initial body weight. In intention-to-treat-analyses, the mean weight loss during one year was 4.8 kg (p < 0.001). Mean BMI decreased by 1.7 kg/m2 (p < 0.001) and waist circumference by 5.6 cm (p < 0.001). Mean muscle mass increased by 3.3% (p < 0.001), and body fat decreased by 5.0% (p < 0.001). After the programme mean visceral fat content was reduced by 6.4%, systolic blood pressure by 8 mmHg (p < 0.001), and diastolic blood pressure by 6 mmHg (p < 0.001). In conclusion, retention to the team-based lifestyle management programme resulted in moderate but significant weight loss with beneficial changes in body composition, and the trend to lose weight was maintained throughout the year. Trial registration: Clinicaltrials.gov identifier NCT04003259.

Adverse influence of bisoprolol on central blood pressure in the upright position: a double-blind placebo-controlled cross-over study.

Treatment with beta-blockers is characterized by inferior reduction of central versus peripheral blood pressure. We examined changes in blood pressure, cardiac function, and vascular resistance after 3 weeks of bisoprolol treatment (5 mg/day) during passive head-up tilt in 16 never-treated Caucasian males with grade I-II primary hypertension. A double-blind, randomized, placebo-controlled cross-over design was applied, and hemodynamics were recorded using continuous tonometric pulse wave analysis and whole-body impedance cardiography. Bisoprolol decreased blood pressure in the aorta (~8/10 mmHg, p ≤ 0.032) and radial artery (~10/9 mmHg, p ≤ 0.037), but upright aortic systolic blood pressure was not significantly reduced (p = 0.085). Bisoprolol reduced heart rate and left cardiac work, and increased subendocardial viability index in supine and upright positions (p ≤ 0.044 for all). Bisoprolol increased stroke volume in the supine (~11 ml, p = 0.02) but not in the upright position, while only upright (~1 l/min, p = 0.007) but not supine cardiac output was reduced. Upright elevation in systemic vascular resistance was increased 2.7-fold (p = 0.002), while upright pulse pressure amplification was decreased by ~20% (p = 0.002) after bisoprolol. Aortic augmentation index, augmentation pressure, and pulse pressure were not changed in the supine position but were increased in the upright position (from 9% to 17%, 3-6 mmHg, and 30-34 mmHg, respectively, p ≤ 0.016 for all). In conclusion, although bisoprolol treatment reduced peripheral blood pressure, central systolic blood pressure in the upright position was not decreased. Importantly, the harmful influences of bisoprolol on central pulse pressure and pressure wave reflection were manifested in the upright position.

Tubular proteinuria and glomerular filtration 6 years after puumala hantavirus-induced acute interstitial nephritis.

BACKGROUND/AIMS: We previously found increased urinary protein excretion, glomerular filtration rate (GFR) and blood pressure in a retrospective analysis of patients with previous nephropathia epidemica (NE). Here, we evaluated the long-term outcome after NE in a prospectively recruited patient group. METHODS: Proteinuria, GFR and ambulatory 24-hour blood pressure were assessed 4-7 years (mean 6) after acute NE in 37 patients, and these values were compared to those from 38 seronegative controls. RESULTS: Six years after NE, the prevalence of elevated urinary alpha(1)-microglobulin excretion was higher in the patients than controls (9/35 vs. 1/38; p = 0.005). The patients also had higher urinary protein excretion (0.17 +/- 0.05 vs. 0.14 +/- 0.04 g/day; p = 0.006), GFR (119 +/- 19 vs. 109 +/- 14 ml/min/1.73 m(2); p = 0.016) and mean systolic (123 +/- 11 vs. 117 +/- 9 mm Hg; p = 0.012), nighttime systolic (109 +/- 11 vs. 100 +/- 9 mm Hg; p = 0.001) and nighttime diastolic blood pressure (70 +/- 7 vs. 66 +/- 7 mm Hg; p = 0.035) than the controls. CONCLUSIONS: These results confirm our previous findings of a higher prevalence of tubular proteinuria and increased urinary protein excretion, GFR and systolic blood pressure 6 years after acute NE.

Glucosuria Predicts the Severity of Puumala Hantavirus Infection.

INTRODUCTION: Puumala hantavirus (PUUV) causes a mild type of hemorrhagic fever with renal syndrome characterized by acute kidney injury (AKI), increased capillary leakage, and thrombocytopenia. Albuminuria and hematuria in dipstick urine test at hospital admission are known to predict the severity of upcoming AKI. METHODS: We analyzed dipstick urine glucose in 195 patients with acute PUUV infection at hospital admission, and divided them into 2 categories according to the presence or absence of glucose in the dipstick urine test. Determinants of disease severity were analyzed in glucosuric and nonglucosuric patients. RESULTS: Altogether, 24 of 195 patients (12%) had glucosuria. The patients with glucosuria had more severe AKI than patients without glucosuria (median maximum creatinine concentration 459 µmol/l, range 78-1041 µmol/l vs. 166 µmol/l, range 51-1499 µmol/l; P < 0.001). The glucosuric patients had more severe thrombocytopenia (median minimum platelet count 41 × 109/l, range 5-102 × 109/l vs. 62 × 109/l, range 3-249 × 109/l; P = 0.006), and more pronounced signs of increased capillary leakage (change in weight, maximum plasma hematocrit, minimum plasma albumin). The glucosuric patients were more often in clinical shock at admission (20.8% vs. 1.2%; P < 0.001) and the length of hospital stay was longer (median 7.5 days, range 4-22 days vs. 6 days, range 2-30 days; P = 0.009). CONCLUSION: Glucosuria is relatively rare, but when present it predicts a more severe disease course in patients with acute PUUV infection.

Liquorice ingestion attenuates vasodilatation via exogenous nitric oxide donor but not via ß2-adrenoceptor stimulation.

We examined the effect of liquorice ingestion on haemodynamic responses to exogenous nitric oxide donor (nitroglycerin) and ß2-adrenoceptor agonist (salbutamol), and 11ß-hydroxysteroid dehydrogenase activity, in 21 volunteers and 21 reference subjects. Haemodynamic data was captured before and after sublingual nitroglycerin (0.25 mg) and inhaled salbutamol (400 µg) during orthostatic challenge utilising radial pulse wave analysis and whole-body impedance cardiography. The recordings were performed at baseline and following two weeks of liquorice intake (290-370 mg/d glycyrrhizin). Urinary cortisone and cortisol metabolites were examined. Liquorice intake elevated aortic systolic and diastolic blood pressure and systemic vascular resistance when compared with the reference group. Following research drug administration the liquorice-induced increase in systemic vascular resistance was observed in the presence of nitroglycerin (p<0.05) but no longer in the presence of salbutamol. Liquorice ingestion decreased cardiac chronotropic response to upright posture (p = 0.032) in unadjusted analysis, but when adjusted for age and sex the difference in the upright change in heart rate was no longer significant. The urinary cortisone to cortisol metabolite ratio decreased from 0.70 to 0.31 (p<0.001) after liquorice intake indicating significant inhibition of the 11ß-hydroxysteroid dehydrogenase type 2. In the reference group the haemodynamic variables remained virtually unchanged. These results suggest that liquorice exposure impaired vasodilatation in vivo that was induced by exogenous nitric oxide donor but not that induced by ß2-adrenoceptor stimulation. Trial registration: EU Clinical Trials Register 2006-002065-39 ClinicalTrials.gov NCT01742702.

Expanding targets of vitamin D receptor activation: downregulation of several RAS components in the kidney.

Vitamin D receptor (VDR) activation has a beneficial influence on the progression of experimental renal insufficiency, and reduced renal tissue renin expression may play a role in this process. Freundlich and co-workers now report that VDR activation also suppresses the expression of angiotensinogen, angiotensin II type 1 receptor, and renin receptor in the kidneys of 5/6 nephrectomized rats, effects associated with reduced blood pressure and urinary protein excretion and with alleviated renal tissue damage.