Heritability, determinants and reference values of renal length: a family-based population study

OBJECTIVES: In this population-based study, reference values were generated for renal length, and the heritability and factors associated with kidney length were assessed. METHODS: Anthropometric parameters and renal ultrasound measurements were assessed in randomly selected nuclear families of European ancestry (Switzerland). The adjusted narrow sense heritability of kidney size parameters was estimated by maximum likelihood assuming multivariate normality after power transformation. Gender-specific reference centiles were generated for renal length according to body height in the subset of non-diabetic non-obese participants with normal renal function. RESULTS: We included 374 men and 419 women (mean ± SD, age 47 ± 18 and 48 ± 17 years, BMI 26.2 ± 4 and 24.5 ± 5 kg/m(2), respectively) from 205 families. Renal length was 11.4 ± 0.8 cm in men and 10.7 ± 0.8 cm in women; there was no difference between right and left renal length. Body height, weight and estimated glomerular filtration rate (eGFR) were positively associated with renal length, kidney function negatively, age quadratically, whereas gender and hypertension were not. The adjusted heritability estimates of renal length and volume were 47.3 ± 8.5 % and 45.5 ± 8.8 %, respectively (P < 0.001). CONCLUSION: The significant heritability of renal length and volume highlights the familial aggregation of this trait, independently of age and body size. Population-based references for renal length provide a useful guide for clinicians. KEY POINTS: • Renal length and volume are heritable traits, independent of age and size. • Based on a European population, gender-specific reference values/percentiles are provided for renal length. • Renal length correlates positively with body length and weight. • There was no difference between right and left renal lengths in this study. • This negates general teaching that the left kidney is larger and longer.

Acute Stroke: Present and Future of Catheter-Based Interventions

Acute ischemic stroke is a major cause of morbidity and mortality in industrialized nations. The sequel of stroke ranges from mild to severe disability and even death. Since the impairment may be permanent, the costs to society from work incapacity and the need for long-term care can be high. Additionally, the burden of suffering associated with the disease may have devastating effects on individuals and families.Following the occlusion of a cerebral vessel, the full extent of the infarction may not become clinically and radiologically apparent until days after. By then, the surrounding watershed zone, or penumbra, either survives or succumbs to necrosis over time. The natural history of this "tissue at risk" is determined by two factors: the collateralization from other vascular territories and the possible occurrence of spontaneous recanalization of the occluded vessel. The current treatment options for acute ischemic stroke are aiming at an early and sustained restoration of flow to the penumbra. The effect of the treatment is therefore time-dependent and the neurologic outcome is a function of the time span between onset of symptoms and recanalization therapy as well as of the recanalization rate associated with a specific treatment.This report summarizes the results of the major trials on catheter-based interventions, either using thrombolytic drugs or novel mechanical approaches being developed to treat patients with acute ischemic stroke.

Internet-Based Interventions for Social Anxiety Disorder - an Overview

Internet-based interventions hold specific advantages and disadvantages in the treatment of social anxiety disorder (SAD). The present review examines different approaches in the internet-based treatment of SAD and reviews their efficacy and effectiveness. 21 studies investigated the potential of guided and unguided internetbased cognitive-behavioral treatments (ICBT) for SAD, comprising a total of N = 1,801 socially anxious individuals. The large majority of these trials reported substantial reductions of social anxiety symptoms through ICBT programs. Within effect sizes were mostly large and comparisons to waitlist and more active control groups were positive. Treatment gains were stable from 3 months to 5 years after treatment termination. In conclusion, ICBT is effective in the reduction of social anxiety symptoms. At the same time, not all participants benefit from these treatments to a sufficient degree. Future research should focus on what makes these interventions work in which patient populations, and at the same time, examine ways to implement internet-based treatment in the routine care for socially anxious patients

Epidemiology of masked and white-coat hypertension: the family-based SKIPOGH study

Objective We investigated factors associated with masked and white-coat hypertension in a Swiss population-based sample. Methods The Swiss Kidney Project on Genes in Hypertension is a family-based cross-sectional study. Office and 24-hour ambulatory blood pressure were measured using validated devices. Masked hypertension was defined as office blood pressure<140/90 mmHg and daytime ambulatory blood pressure≥135/85 mmHg. White-coat hypertension was defined as office blood pressure≥140/90 mmHg and daytime ambulatory blood pressure<135/85 mmHg. Mixed-effect logistic regression was used to examine the relationship of masked and white-coat hypertension with associated factors, while taking familial correlations into account. High-normal office blood pressure was defined as systolic/diastolic blood pressure within the 130–139/85–89 mmHg range. Results Among the 652 participants included in this analysis, 51% were female. Mean age (±SD) was 48 (±18) years. The proportion of participants with masked and white coat hypertension was respectively 15.8% and 2.6%. Masked hypertension was associated with age (odds ratio (OR) = 1.02, p = 0.012), high-normal office blood pressure (OR = 6.68, p<0.001), and obesity (OR = 3.63, p = 0.001). White-coat hypertension was significantly associated with age (OR = 1.07, p<0.001) but not with education, family history of hypertension, or physical activity. Conclusions Our findings suggest that physicians should consider ambulatory blood pressure monitoring for older individuals with high-normal office blood pressure and/or who are obese.

Reference Values and Factors Associated With Renal Resistive Index in a Family-Based Population Study

Increased renal resistive index (RRI) has been recently associated with target organ damage and cardiovascular or renal outcomes in patients with hypertension and diabetes mellitus. However, reference values in the general population and information on familial aggregation are largely lacking. We determined the distribution of RRI, associated factors, and heritability in a population-based study. Families of European ancestry were randomly selected in 3 Swiss cities. Anthropometric parameters and cardiovascular risk factors were assessed. A renal Doppler ultrasound was performed, and RRI was measured in 3 segmental arteries of both kidneys. We used multilevel linear regression analysis to explore the factors associated with RRI, adjusting for center and family relationships. Sex-specific reference values for RRI were generated according to age. Heritability was estimated by variance components using the ASSOC program (SAGE software). Four hundred women (mean age±SD, 44.9±16.7 years) and 326 men (42.1±16.8 years) with normal renal ultrasound had mean RRI of 0.64±0.05 and 0.62±0.05, respectively (P<0.001). In multivariable analyses, RRI was positively associated with female sex, age, systolic blood pressure, and body mass index. We observed an inverse correlation with diastolic blood pressure and heart rate. Age had a nonlinear association with RRI. We found no independent association of RRI with diabetes mellitus, hypertension treatment, smoking, cholesterol levels, or estimated glomerular filtration rate. The adjusted heritability estimate was 42±8% (P<0.001). In a population-based sample with normal renal ultrasound, RRI normal values depend on sex, age, blood pressure, heart rate, and body mass index. The significant heritability of RRI suggests that genes influence this phenotype.

CYP17A1 Enzyme Activity Is Linked to Ambulatory Blood Pressure in a Family-Based Population Study

BACKGROUND Genome-wide association studies have linked CYP17A1 coding for the steroid hormone synthesizing enzyme 17α-hydroxylase (CYP17A1) to blood pressure (BP). We hypothesized that the genetic signal may translate into a correlation of ambulatory BP (ABP) with apparent CYP17A1 activity in a family-based population study and estimated the heritability of CYP17A1 activity. METHODS In the Swiss Kidney Project on Genes in Hypertension, day and night urinary excretions of steroid hormone metabolites were measured in 518 participants (220 men, 298 women), randomly selected from the general population. CYP17A1 activity was assessed by 2 ratios of urinary steroid metabolites: one estimating the combined 17α-hydroxylase/17,20-lyase activity (ratio 1) and the other predominantly 17α-hydroxylase activity (ratio 2). A mixed linear model was used to investigate the association of ABP with log-transformed CYP17A1 activities exploring effect modification by urinary sodium excretion. RESULTS Daytime ABP was positively associated with ratio 1 under conditions of high, but not low urinary sodium excretion (P interaction <0.05). Ratio 2 was not associated with ABP. Heritability estimates (SE) for day and night CYP17A1 activities were 0.39 (0.10) and 0.40 (0.09) for ratio 1, and 0.71 (0.09) and 0.55 (0.09) for ratio 2 (P values <0.001). CYP17A1 activities, assessed with ratio 1, were lower in older participants. CONCLUSIONS Low apparent CYP17A1 activity (assessed with ratio 1) is associated with elevated daytime ABP when salt intake is high. CYP17A1 activity is heritable and diminished in the elderly. These observations highlight the modifying effect of salt intake on the association of CYP17A1 with BP.

The InterHerz project--a web-based psychological treatment for cardiac patients with depression: study protocol of a randomized controlled trial

Patients with heart disease often suffer from difficulties in psychological adaptation during cardiac rehabilitation. Mood disorders such as depression are known to be highly prevalent in cardiac patients and to have a negative impact on the progression of coronary heart disease. However, cardiac patients have difficulties to get psychological treatments due to low availability and motivational difficulties. Web-based interventions have been proven to be effective in treating depressive symptoms. Deprexis is a promising web-based psychological treatment which was devised for depressed patients. The aim of the study InterHerz is to examine if Deprexis is an effective psychological treatment to reduce stress and depression in cardiac patients.

Retention in care under universal antiretroviral therapy for HIV-infected pregnant and breastfeeding women ('Option B+') in Malawi

OBJECTIVE To explore the levels and determinants of loss to follow-up (LTF) under universal lifelong antiretroviral therapy (ART) for pregnant and breastfeeding women ('Option B+') in Malawi. DESIGN, SETTING, AND PARTICIPANTS We examined retention in care, from the date of ART initiation up to 6 months, for women in the Option B+ program. We analysed nationwide facility-level data on women who started ART at 540 facilities (n = 21 939), as well as individual-level data on patients who started ART at 19 large facilities (n = 11 534). RESULTS Of the women who started ART under Option B+ (n = 21 939), 17% appeared to be lost to follow-up 6 months after ART initiation. Most losses occurred in the first 3 months of therapy. Option B+ patients who started therapy during pregnancy were five times more likely than women who started ART in WHO stage 3/4 or with a CD4 cell count 350 cells/μl or less, to never return after their initial clinic visit [odds ratio (OR) 5.0, 95% confidence interval (CI) 4.2-6.1]. Option B+ patients who started therapy while breastfeeding were twice as likely to miss their first follow-up visit (OR 2.2, 95% CI 1.8-2.8). LTF was highest in pregnant Option B+ patients who began ART at large clinics on the day they were diagnosed with HIV. LTF varied considerably between facilities, ranging from 0 to 58%. CONCLUSION Decreasing LTF will improve the effectiveness of the Option B+ approach. Tailored interventions, like community or family-based models of care could improve its effectiveness.

Physical activity interventions in schools for improving lifestyle in European countries

Background: In the last decades, children’s and adolescents’ obesity and overweight have increased in European Countries. Unhealthy eating habits and sedentary lifestyle have been recognized to determine such an epidemic. Schools represent an ideal setting to modify harmful behaviors, and physical activity could be regarded as a potential way to avoid the metabolic risks related to obesity. Methods: A systematic review of the literature was carried out to summarize the evidence of school-based interventions aimed to promote, enhance and implement physical activity in European schools. Only randomized controlled trials were included, carried out in Europe from January 2000 to April 2014, universally delivered and targeting pupils aged between 3 and 18 years old. Results: Forty-seven studies were retrieved based either on multicomponent interventions or solely physical activity programs. Most aimed to prevent obesity and cardiovascular risks among youths. While few studies showed a decrease in BMI, positive results were achieved on other outcomes, such as metabolic parameters and physical fitness. Conclusion: Physical activity in schools should be regarded as a simple, non-expensive and enjoyable way to reach all the children and adolescents with adequate doses of moderate to vigorous physical activity.

Inactive Matrix Gla-Protein Is Associated With Arterial Stiffness in an Adult Population-Based Study

Increased pulse wave velocity (PWV) is a marker of aortic stiffness and an independent predictor of mortality. Matrix Gla-protein (MGP) is a vascular calcification inhibitor that needs vitamin K to be activated. Inactive MGP, known as desphospho-uncarboxylated MGP (dp-ucMGP), can be measured in plasma and has been associated with various cardiovascular markers, cardiovascular outcomes, and mortality. In this study, we hypothesized that high levels of dp-ucMGP are associated with increased PWV. We recruited participants via a multicenter family-based cross-sectional study in Switzerland. Dp-ucMGP was quantified in plasma by sandwich ELISA. Aortic PWV was determined by applanation tonometry using carotid and femoral pulse waveforms. Multiple regression analysis was performed to estimate associations between PWV and dp-ucMGP adjusting for age, renal function, and other cardiovascular risk factors. We included 1001 participants in our analyses (475 men and 526 women). Mean values were 7.87±2.10 m/s for PWV and 0.43±0.20 nmol/L for dp-ucMGP. PWV was positively associated with dp-ucMGP both before and after adjustment for sex, age, body mass index, height, systolic and diastolic blood pressure (BP), heart rate, renal function, low- and high-density lipoprotein, glucose, smoking status, diabetes mellitus, BP and cholesterol lowering drugs, and history of cardiovascular disease (P≤0.01). In conclusion, high levels of dp-ucMGP are independently and positively associated with arterial stiffness after adjustment for common cardiovascular risk factors, renal function, and age. Experimental studies are needed to determine whether vitamin K supplementation slows arterial stiffening by increasing MGP carboxylation.

Sociodemographic, behavioral and genetic determinants of allostatic load in a Swiss population-based study.

Allostatic load (AL) is a marker of physiological dysregulation which reflects exposure to chronic stress. High AL has been related to poorer health outcomes including mortality. We examine here the association of socioeconomic and lifestyle factors with AL. Additionally, we investigate the extent to which AL is genetically determined. We included 803 participants (52% women, mean age 48±16years) from a population and family-based Swiss study. We computed an AL index aggregating 14 markers from cardiovascular, metabolic, lipidic, oxidative, hypothalamus-pituitary-adrenal and inflammatory homeostatic axes. Education and occupational position were used as indicators of socioeconomic status. Marital status, stress, alcohol intake, smoking, dietary patterns and physical activity were considered as lifestyle factors. Heritability of AL was estimated by maximum likelihood. Women with a low occupational position had higher AL (low vs. high OR=3.99, 95%CI [1.22;13.05]), while the opposite was observed for men (middle vs. high OR=0.48, 95%CI [0.23;0.99]). Education tended to be inversely associated with AL in both sexes(low vs. high OR=3.54, 95%CI [1.69;7.4]/OR=1.59, 95%CI [0.88;2.90] in women/men). Heavy drinking men as well as women abstaining from alcohol had higher AL than moderate drinkers. Physical activity was protective against AL while high salt intake was related to increased AL risk. The heritability of AL was estimated to be 29.5% ±7.9%. Our results suggest that generalized physiological dysregulation, as measured by AL, is determined by both environmental and genetic factors. The genetic contribution to AL remains modest when compared to the environmental component, which explains approximately 70% of the phenotypic variance.

1D.03: Inactive Matrix Gla Protein is Assocated with Renal Resistive Index in a Population-Based Study

OBJECTIVE Renal resistive index (RRI) varies directly with renal vascular stiffness and pulse pressure. RRI correlates positively with arteriolosclerosis in damaged kidneys and predicts progressive renal dysfunction. Matrix Gla-protein (MGP) is a vascular calcification inhibitor that needs vitamin K to be activated. Inactive MGP, known as desphospho-uncarboxylated MGP (dp-ucMGP), can be measured in plasma and has been associated with various cardiovascular (CV) markers, CV outcomes and mortality. In this study we hypothesize that increased RRI is associated with high levels of dp-ucMGP. DESIGN AND METHOD We recruited participants via a multi-center family-based cross-sectional study in Switzerland exploring the role of genes and kidney hemodynamics in blood pressure regulation. Dp-ucMGP was quantified in plasma samples by sandwich ELISA. Renal doppler sonography was performed using a standardized protocol to measure RRIs on 3 segmental arteries in each kidney. The mean of the 6 measures was reported. Multiple regression analysis was performed to estimate associations between RRI and dp-ucMGP adjusting for sex, age, pulse pressure, mean pressure, renal function and other CV risk factors. RESULTS We included 1035 participants in our analyses. Mean values were 0.64 ± 0.06 for RRI and 0.44 ± 0.21 (nmol/L) for dp-ucMGP. RRI was positively associated with dp-ucMGP both before and after adjustment for sex, age, body mass index, pulse pressure, mean pressure, heart rate, renal function, low and high density lipoprotein, smoking status, diabetes, blood pressure and cholesterol lowering drugs, and history of CV disease (P < 0.001). CONCLUSIONS RRI is independently and positively associated with high levels of dp-ucMGP after adjustment for pulse pressure and common CV risk factors. Further studies are needed to determine if vitamin K supplementation can have a positive effect on renal vascular stiffness and kidney function.