Frequency in hypertensives of alleles for a RFLP associated with the renin gene

The genetic basis of primary hypertension is not known. Renin is important in blood pressure and volume control and a HindIII restriction fragment length polymorphism (RFLP) is present within the human renin gene locus. To examine whether there is a relationship between this RFLP and primary hypertension, DNA and renin analyses were performed on leukocytes and plasma from hypertensive and normotensive individuals. In hypertensives the frequencies of alleles for the HindIII RFLP were found to be 0.55 and 0.45, compared with 0.60 and 0.40 in the total population of 231 subjects examined, a difference that was not statistically significant. There also appeared to be no significant difference in renin activity in plasma for hypertensive patients of each genotype, nor in their pre- or post-treatment blood pressures. We thus conclude that, within the limits of the present study, the suspected genetic abnormalities associated with primary hypertension in man do not appear to be related to a HindIII RFLP in the renin gene.

Scanning the genome for essential hypertension loci

1. Essential hypertension occurs in people with an underlying genetic predisposition who subject themselves to adverse environmental influences. The number of genes involved is unknown, as is the extent to which each contributes to final blood pressure and the severity of the disease. 2. In the past, studies of potential candidate genes have been performed by association (case-control) analysis of unrelated individuals or linkage (pedigree or sibpair) analysis of families. These studies have resulted in several positive findings but, as one may expect, also an enormous number of negative results. 3. In order to uncover the major genetic loci for essential hypertension, it is proposed that scanning the genome systematically in 100- 200 affected sibships should prove successful. 4. This involves genotyping sets of hypertensive sibships to determine their complement of several hundred microsatellite polymorphisms. Those that are highly informative, by having a high heterozygosity, are most suitable. Also, the markers need to be spaced sufficiently evenly across the genome so as to ensure adequate coverage. 5. Tests are performed to determine increased segregation of alleles of each marker with hypertension. The analytical tools involve specialized statistical programs that can detect such differences. Non- parametric multipoint analysis is an appropriate approach. 6. In this way, loci for essential hypertension are beginning to emerge.

Association of a low density lipoprotein receptor microsatellite variant with obesity

OBJECTIVE To determine whether a microsatellite polymorphism located towards the 3' end of the low density lipoprotein receptor gene (LDLR) is associated with obesity. DESIGN A cross-sectional case-control study. SUBJECTS One hundred and seven obese individuals, defined as a body mass index (BMI) ≤ 26 kg/m2, and 163 lean individuals, defined as a BMI < 26 kg/m2. MEASUREMENTS BMI, blood pressure, serum lipids, alleles of LDLR microsatellite (106 bp, 108 bp and 112 bp). RESULTS There was a significant association between variants of the LDLR microsatellite and obesity, in the overall tested population, due to a contributing effect in females (χ2 = 12.3, P = 0.002), but not in males (χ2 = 0.3, P = 0.87). In females, individuals with the 106 bp allele were more likely to be lean, while individuals with the 112 bp and/or 108 bp alleles tended to be obese. CONCLUSIONS These results suggest that in females, LDLR may play a role in the development of obesity.

Applying the ecological model of behavior change to a physical activity trial in retirement communities : description of the study protocol

Objectives To describe the intervention protocol for the first multilevel ecological intervention for physical activity in retirement communities that addresses individual, interpersonal and community influences on behavior change. Design A cluster randomized controlled trial design was employed with two study arms: a physical activity intervention and an attention control successful aging condition. Setting Sixteen continuing care retirement communities in San Diego County. Participants Three hundred twenty older adults, aged 65 years and older, are being recruited to participate in the trial. In addition, peer leaders are being recruited to lead some study activities, especially to sustain the intervention after study activities ceased. Intervention Participants in the physical activity trial receive individual, interpersonal and community intervention components. The individual level components include pedometers, goal setting and individual phone counseling. The interpersonal level components include group education sessions and peer-led activities. The community level components include resource audits and enumeration, tailored walking maps, and community improvement projects. The successful aging group receives individual and group attention about successful aging topics. Measurements The main outcome is light to moderate physical activity, measured objectively by accelerometry. Other objective outcomes included physical functioning, blood pressure, physical fitness, and cognitive functioning. Self report measures include depressive symptoms and health related quality of life. Results The intervention is being delivered successfully in the communities and compliance rates are high. Conclusion Ecological Models call for interventions that address multiple levels of the model. Previous studies have not included components at each level and retirement communities provide a model environment to demonstrate how to implement such an intervention.

Exposure to ambient heat and urolithiasis among outdoor workers in Guangzhou, China

Objectives: To assess the impact of exposure to ambient heat on urolithiasis among outdoor workers in a subtropical city of China. Methods: The 2003–2010 health check data of a shipbuilding company in Guangzhou, China were acquired. 190 cases and 760 matched controls were involved in this study. We assessed the relationship between exposure to ambient heat and urolithiasis for different occupations using conditional logistic regression. Results: Spray painters were most likely to develop urolithiasis (OR = 4.4; 95% CI: 1.7, 11.4), followed by smelter workers (OR = 4.0; 95% CI: 1.8, 9.2), welders (OR = 3.7; 95% CI: 1.9, 7.2), production security and quality inspectors (OR = 2.7; 95% CI: 1.4, 3.0), and assemblers (OR = 2.2; 95% CI: 1.1, 4.3). Overall, outdoor workers were more likely to present with urolithiasis compared with indoor employees (p b 0.05). In addition, workers with longer cumulative exposure time (OR = 1.5; 95% CI: 1.2, 1.8) and abnormal blood pressure (OR = 1.6; 95% CI: 1.0, 2.5) had higher risk for urolithiasis. Conclusions: Our findings demonstrate a significant association between exposure to ambient heat and urolithiasis among outdoor working populations. Public health intervention strategies should be developed to specifically target outdoor occupations.

Mapping eQTLs in the Norfolk Island genetic isolate identifies candidate genes for CVD risk traits

Cardiovascular disease (CVD) affects millions of people worldwide and is influenced by numerous factors, including lifestyle and genetics. Expression quantitative trait loci (eQTLs) influence gene expression and are good candidates for CVD risk. Founder-effect pedigrees can provide additional power to map genes associated with disease risk. Therefore, we identified eQTLs in the genetic isolate of Norfolk Island (NI) and tested for associations between these and CVD risk factors. We measured genome-wide transcript levels of blood lymphocytes in 330 individuals and used pedigree-based heritability analysis to identify heritable transcripts. eQTLs were identified by genome-wide association testing of these transcripts. Testing for association between CVD risk factors (i.e., blood lipids, blood pressure, and body fat indices) and eQTLs revealed 1,712 heritable transcripts (p < 0.05) with heritability values ranging from 0.18 to 0.84. From these, we identified 200 cis-acting and 70 trans-acting eQTLs (p < 1.84 × 10(-7)) An eQTL-centric analysis of CVD risk traits revealed multiple associations, including 12 previously associated with CVD-related traits. Trait versus eQTL regression modeling identified four CVD risk candidates (NAAA, PAPSS1, NME1, and PRDX1), all of which have known biological roles in disease. In addition, we implicated several genes previously associated with CVD risk traits, including MTHFR and FN3KRP. We have successfully identified a panel of eQTLs in the NI pedigree and used this to implicate several genes in CVD risk. Future studies are required for further assessing the functional importance of these eQTLs and whether the findings here also relate to outbred populations.

Determinants and treatment of hypertension in South Africans: The first demographic and health survey

Objectives: To identify the groups of patients with high prevalence and poor control of hypertension in South Africa. Methods: In the first national Demographic and Health Survey, 12 952 randomly selected South Africans, aged 15 years and older were surveyed. Trained interviewers completed questionnaires on socio-demographic characteristics, lifestyle and the management of hypertension. This cross-sectional survey also included blood pressure, height and weight measurements. Logistic regression analyses identified the determinants of hypertension and the treatment status in this dataset. Results: A high risk of hypertension was associated with less than tertiary education, older age groups, overweight and obese people, using alcohol in excess, and a family history of stroke and hypertension. Rural Africans had the lowest risk of hypertension, which was significantly higher in obese African women than in women with normal body mass index. Improved hypertension control was found in the wealthy, women, older persons, being Asian, and having medical insurance. Conclusions: Rural African people had lower hypertension prevalence rates than the other groups. The poorer, younger men, without health insurance had the worst level of hypertension control.

The primacy of vital signs – Acute care nurses’ and midwives’ use of physical assessment skills: A cross sectional study

BACKGROUND: Registered nurses and midwives play an essential role in detecting patients at risk of deterioration through ongoing assessment and action in response to changing health status. Yet, evidence suggests that clinical deterioration frequently goes unnoticed in hospitalised patients. While much attention has been paid to early warning and rapid response systems, little research has examined factors related to physical assessment skills. OBJECTIVES: To determine a minimum data set of core skills used during nursing assessment of hospitalised patients and identify nurse and workplace predictors of the use of physical assessment to detect patient deterioration. DESIGN: The study used a single-centre, cross-sectional survey design. SETTING and PARTICIPANTS: The study included 434 registered nurses and midwives (Grades 5-7) involved in clinical care of patients on acute care wards, including medicine, surgery, oncology, mental health and maternity service areas, at a 929-bed tertiary referral teaching hospital in Southeast Queensland, Australia. METHODS: We conducted a hospital-wide survey of registered nurses and midwives using the 133-item Physical Assessment Skills Inventory and the 58-item Barriers to Registered Nurses’ Use of Physical Assessment scale. Median frequency for each physical assessment skill was calculated to determine core skills. To explore predictors of core skill utilisation, backward stepwise general linear modelling was conducted. Means and regression coefficients are reported with 95% confidence intervals. A p value < .05 was considered significant for all analyses. RESULTS: Core skills used by most nurses every time they worked included assessment of temperature, oxygen saturation, blood pressure, breathing effort, skin, wound and mental status. Reliance on others and technology (F = 35.77, p < .001), lack of confidence (F = 5.52, p = .02), work area (F = 3.79, p = .002), and clinical role (F = 44.24, p < .001) were significant predictors of the extent of physical assessment skill use. CONCLUSIONS: The increasing acuity of the acute care patient plausibly warrants more than vital signs assessment; however, our study confirms nurses’ physical assessment core skill set is mainly comprised of vital signs. The focus on these endpoints of deterioration as dictated by early warning and rapid response systems may divert attention from and devalue comprehensive nursing assessment that could detect subtle changes in health status earlier in the patient's hospitalisation.

Hydrotherapy as a recovery strategy after exercise: A pragmatic controlled trial

Background Our aim was to evaluate the recovery effects of hydrotherapy after aerobic exercise in cardiovascular, performance and perceived fatigue. Methods A pragmatic controlled repeated measures; single-blind trial was conducted. Thirty-four recreational sportspeople visited a Sport-Centre and were assigned to a Hydrotherapy group (experimental) or rest in a bed (control) after completing a spinning session. Main outcomes measures including blood pressure, heart rate, handgrip strength, vertical jump, self-perceived fatigue, and body temperature were assessed at baseline, immediately post-exercise and post-recovery. The hypothesis of interest was the session*time interaction. Results The analysis revealed significant session*time interactions for diastolic blood pressure (P=0.031), heart rate (P=0.041), self perceived fatigue (P=0.046), and body temperature (P=0.001); but not for vertical jump (P=0.437), handgrip (P=0.845) or systolic blood pressure (P=0.266). Post-hoc analysis revealed that hydrotherapy resulted in recovered heart rate and diastolic blood pressure similar to baseline values after the spinning session. Further, hydrotherapy resulted in decreased self-perceived fatigue after the spinning session. Conclusions Our results support that hydrotherapy is an adequate strategy to facilitate cardiovascular recovers and perceived fatigue, but not strength, after spinning exercise. Trial registration ClinicalTrials.gov Identifier: NCT01765387 Keywords: Hydrotherapy; Heart rate; Fatigue; Strength; Blood pressure; Body temperature

Fatigue crack growth under pulsatile pressure and plaque rupture

Identification of vulnerable plaque pre-rupture is extremely important for patient risk stratification. The mechanism of plaque rupture is still not entirely clear, but it is thought to be a process involving multiple factors. From a biomechanical viewpoint, plaque rupture is usually seen as a structural failure when the plaque cannot resist the hemodynamic blood pressure and shear stress exerted on it. However, the cardiovascular system is naturally a cyclical hemodynamic environment, and myocardial infarction can be a symptomatically quiescent but potentially progressive process when plaque ruptures at stresses much lower than its strength. Therefore, fatigue accumulation is a possible mechanism for plaque rupture. In this study, a crack growth model was developed, and the previously-mentioned hypothesis was tested by conducting a comparative study between 18 symptomatic and 16 asymptomatic patients with carotid stenosis.

Impact of coronary tortuosity on coronary pressure: Numerical simulation study

Background: Coronary tortuosity (CT) is a common coronary angiographic finding. Whether CT leads to an apparent reduction in coronary pressure distal to the tortuous segment of the coronary artery is still unknown. The purpose of this study is to determine the impact of CT on coronary pressure distribution by numerical simulation. Methods: 21 idealized models were created to investigate the influence of coronary tortuosity angle (CTA) and coronary tortuosity number (CTN) on coronary pressure distribution. A 2D incompressible Newtonian flow was assumed and the computational simulation was performed using finite volume method. CTA of 30°, 60°, 90°, 120° and CTN of 0, 1, 2, 3, 4, 5 were discussed under both steady and pulsatile conditions, and the changes of outlet pressure and inlet velocity during the cardiac cycle were considered. Results: Coronary pressure distribution was affected both by CTA and CTN. We found that the pressure drop between the start and the end of the CT segment decreased with CTA, and the length of the CT segment also declined with CTA. An increase in CTN resulted in an increase in the pressure drop. Conclusions: Compared to no-CT, CT can results in more decrease of coronary blood pressure in dependence on the severity of tortuosity and severe CT may cause myocardial ischemia.

Shared common variants in prostate cancer and blood lipids

Background Epidemiological and clinical studies suggest comorbidity between prostate cancer (PCA) and cardiovascular disease (CVD) risk factors. However, the relationship between these two phenotypes is still not well understood. Here we sought to identify shared genetic loci between PCA and CVD risk factors. Methods We applied a genetic epidemiology method based on conjunction false discovery rate (FDR) that combines summary statistics from different genome-wide association studies (GWAS), and allows identification of genetic overlap between two phenotypes. We evaluated summary statistics from large, multi-centre GWA studies of PCA (n = 50 000) and CVD risk factors (n = 200 000) [triglycerides (TG), low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol, systolic blood pressure, body mass index, waist-hip ratio and type 2 diabetes (T2D)]. Enrichment of single nucleotide polymorphisms (SNPs) associated with PCA and CVD risk factors was assessed with conditional quantile-quantile plots and the Anderson-Darling test. Moreover, we pinpointed shared loci using conjunction FDR. Results We found the strongest enrichment of P-values in PCA was conditional on LDL and conditional on TG. In contrast, we found only weak enrichment conditional on HDL or conditional on the other traits investigated. Conjunction FDR identified altogether 17 loci; 10 loci were associated with PCA and LDL, 3 loci were associated with PCA and TG and additionally 4 loci were associated with PCA, LDL and TG jointly (conjunction FDR < 0.01). For T2D, we detected one locus adjacent to HNF1B. Conclusions We found polygenic overlap between PCA predisposition and blood lipids, in particular LDL and TG, and identified 17 pleiotropic gene loci between PCA and LDL, and PCA and TG, respectively. These findings provide novel pathobiological insights and may have implications for trials using targeting lipid-lowering agents in a prevention or cancer setting.

Expression and function of angiotensins in the regulation of intraocular pressure - an experimental study

Glaucoma is a multifactorial long-term ocular neuropathy associated with progressive loss of the visual field, retinal nerve fiber structural abnormalities and optic disc changes. Like arterial hypertension it is usually a symptomless disease, but if left untreated leads to visual disability and eventual blindness. All therapies currently used aim to lower intraocular pressure (IOP) in order to minimize cell death. Drugs with new mechanisms of action could protect glaucomatous eyes against blindness. Renin-angiotensin system (RAS) is known to regulate systemic blood pressure and compounds acting on it are in wide clinical use in the treatment of hypertension and heart failure but not yet in ophthalmological use. There are only few previous studies concerning intraocular RAS, though evidence is accumulating that drugs antagonizing RAS can also lower IOP, the only treatable risk factor in glaucoma. The main aim of this experimental study was to clarify the expression of the renin-angiotensin system in the eye tissues and to test its potential oculohypotensive effects and mechanisms. In addition, the possible relationship between the development of hypertension and IOP was evaluated in animal models. In conclusion, a novel angiotensin receptor type (Mas), as well as ACE2 enzyme- producing agonists for Mas, were described for the first time in the eye structures participating in the regulation of IOP. In addition, a Mas receptor agonist significantly reduced even normal IOP. The effect was abolished by a specific receptor antagonist. Intraocular, local RAS would thus to be involved in the regulation of IOP, probably even more in pathological conditions such as glaucoma though there was no unambiguous relationship between arterial and ocular hypertension. The findings suggest the potential as antiglaucomatous drugs of agents which increase ACE2 activity and the formation of angiotensin (1-7), or activate Mas receptors.

G-protein beta3 subunit gene (GNB3) variant in causation of essential hypertension

-Essential hypertensives display enhanced signal transduction through pertussis toxin-sensitive G proteins. The T allele of a C825T variant in exon 10 of the G protein beta3 subunit gene (GNB3) induces formation of a splice variant (Gbeta3-s) with enhanced activity. The T allele of GNB3 was shown recently to be associated with hypertension in unselected German patients (frequency=0.31 versus 0.25 in control). To confirm and extend this finding in a different setting, we performed an association study in Australian white hypertensives. This involved an extensively examined cohort of 110 hypertensives, each of whom were the offspring of 2 hypertensive parents, and 189 normotensives whose parents were both normotensive beyond age 50 years. Genotyping was performed by polymerase chain reaction and digestion with BseDI, which either cut (C allele) or did not cut (T allele) the 268-bp polymerase chain reaction product. T allele frequency in the hypertensive group was 0.43 compared with 0.25 in the normotensive group (chi2=22; P=0.00002; odds ratio=2.3; 95% CI=1.7 to 3.3). The T allele tracked with higher pretreatment blood pressure: diastolic=105+/-7, 109+/-16, and 128+/-28 mm Hg (mean+/-SD) for CC, CT, and TT, respectively (P=0.001 by 1-way ANOVA). Blood pressures were higher in female hypertensives with a T allele (P=0.006 for systolic and 0.0003 for diastolic by ANOVA) than they were in male hypertensives. In conclusion, the present study of a group with strong family history supports a role for a genetically determined, physiologically active splice variant of the G protein beta3 subunit gene in the causation of essential hypertension.