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Background: Anthropometry is emerging as a useful tool in assessing the future risk of chronic diseases such as type 2 diabetes mellitus (and diabetic nephropathy, diabetic neuropathy, diabetic retinopathy), hypercholesterolemia, atherosclerosis, coronary artery diseases, nonalcoholic fatty liver disease (NAFLD). Body mass index (BMI) and waist-hip ratio (WHR) are used extensively in the forecast of cardio-vascular diseases. The main risk factor for such diseases is hypertension and the correlation of hypertension with BMI and/or WHR gives one the ability to forecast the diseases as risk assessment from a young age and proper techniques can be utilized to delay them. The aim of this study was to correlate BMI and WHR with hypertension in young adults and adolescents. Material and methods: A cross sectional, record-based study of adolescents from age group 17-19 (n = 946) was done and analyzed. Results: Data of a total of 465 males and 481 females (n = 946) were analyzed. In both males and females, mean blood pressure [both systolic (SBP) and diastolic blood pressure (DBP)] showed a positive correlation with increasing ranges of BMI and WHR. Values of Pearson correlation coefficient and p-value: Males: SBP -> BMI = 0.236 (p < 0.0001); DBP -> BMI = 0.187 (p < 0.0001); Males: SBP -> WHR = 0.194 (p < 0.0001); DBP -> WHR = 0.148 (p < 0.0001); Females: SBP -> BMI = 0.249 (p <0.0001); DBP -> BMI = 0.267 (p < 0.0001); Females: SBP -> WHR = 0.090 (p < 0.0001); DBP -> WHR= 0.116 (p < 0.0001). The correlation between BMI and WHR in males was 0.234 (p < 0.0001) and in females, it was 0.172 (p < 0.0001). Conclusion: A steady increase in SBP and DBP is correlated with an increase in BMI and WHR. This leads to the efficacy of these methods in assessing future risks. It was found that hypertension was correlated with BMI and WHR; there was also a correlation between BMI and WHR. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MS) and its components are associated with greater cardiovascular risk. A number of studies found a positive association between MS and vascular damage, but few observational studies evaluated the predictive role of MS on arterial stiffening (AS). Therefore, the aim of this study was to estimate the ability of MS and its components to predict the risk of AS in an 8-year follow-up of a sample of adult men (Olivetti Heart Study). The analysis included 778 men without AS (pulse pressure >60 mmHg) at baseline. A positive diagnosis of MS was made by recognized criteria, if at least three components were present. At the end of the follow-up period, there was an incidence of 11% in AS. The percentage of participants that developed AS was greater in the MS group than those without MS, also after adjustment for main confounders (odds ratio: 2.5, 95% confidence interval: 1.3–4.9). The risk of AS also increased with increase in the numbers of MS elements (p for trend <.01). In addition, the analysis of the predictive role of the single MS component showed that high blood pressure (HBP) was the strongest predictor. The results of this prospective study indicate a predictive role of MS on AS, independently of main confounders. In addition, HBP seems the strongest predictor of AS among MS components. [ABSTRACT FROM AUTHOR]

BACKGROUND We investigated proximal and distal renal tubular sodium handling, as assessed by fractional excretion of lithium (FELi) and fractional distal reabsorption rate of sodium (FDRNa), in relation to environmental and genetic factors in untreated patients. METHODS Our study participants were suspected hypertensive patients being off antihypertensive medication for ≥2 weeks and referred for 24-hour ambulatory blood pressure monitoring. We collected serum and 24-hour urine for measurement of sodium, creatinine, and lithium concentration, and calculated FELi and FDRNa. We genotyped 19 single-nucleotide polymorphisms associated with renal sodium handling or blood pressure using the ABI SNapShot method. RESULTS The 1,409 participants (664 men, 47.1%) had a mean (±SD) age of 51.0 ± 10.5 years. After adjustment for host factors, both FELi and FDRNa were significantly (P ≤ 0.01) associated with season and humidity, explaining ~1.3% and ~3.5% of the variance, respectively. FELi was highest in autumn and lowest in summer and intermediate in spring and winter (P = 0.007). FDRNa was also highest in autumn but lowest in winter and intermediate in spring and summer (P < 0.001). Neither FELi nor FDRNa was associated with outdoor temperature or atmospheric pressure (P ≥ 0.13). After adjustment for host and environmental factors and Bonferroni multiple testing, among the 19 studied genetic variants, only rs12513375 was significantly associated with FELi and FDRNa (P ≤ 0.004) and explained about 1.7% of the variance. CONCLUSIONS Renal sodium handling as measured by endogenous lithium clearance was sensitive to major environmental and genetic factors. Our finding is toward the use of these indexes for the definition of renal tubular dysfunction. [ABSTRACT FROM AUTHOR]

BACKGROUND Insulin resistance and renal tubular sodium handling influence arterial structure and function and play an essential role in salt-sensitive forms of hypertension. METHODS In a population with prevailing sodium consumption, we assessed the relationship between cardiovascular phenotypes (peripheral and central blood pressures, elastic properties of large arteries, the left ventricular structure) and sodium handling parameters (daily urinary sodium excretion, fractional urinary lithium excretion in proximal—FELi and distal tubules), as a function of insulin sensitivity—measured by homeostasis model assessment–insulin resistance (HOMA-IR), leptin-to-adiponectin (L/A) ratio, and homeostasis model assessment–adiponectin (HOMA-AD). RESULTS In patients with FELi below the median value (corresponding to the group with increased proximal sodium reabsorption) and higher insulin resistance as measured by HOMA-IR, pulse wave augmentation indexes were significantly higher—AIxP (99.4% vs. 86.2%; P = 0.007), AIxC1 (159.4% vs. 144.2%; P = 0.04), and AIxC2 (36.1% vs. 28.3%; P = 0.02), than in patients with lower insulin resistance. The same trend was observed in relation to L/A ratio—AIxP (98.7% vs. 87.1%; P = 0.005), AIxC1 (158.6% vs. 144.5%; P = 0.02), and AIxC2 (35.6% vs. 28.5%; P = 0.01) and HOMA-AD—AIxP (99.7% vs. 83.8%; P = 0.001), AIxC1 (160.5% vs. 140.3%; P = 0.007), and AIxC2 (36.6% vs. 26.3%; P = 0.003). Such relationships were not observed in patients with FELi above the median value. CONCLUSIONS In the hypertensive population with prevailing sodium intake, insulin resistance and increased sodium reabsorption in proximal tubules may affect arterial wall function. [ABSTRACT FROM AUTHOR]

Objective:The prevailing focus regarding eating behaviour is on restriction, concern, worry and pathology. In contrast, the purpose of the present studies was to focus on a positive relationship with eating in non-clinical samples from Germany, the USA and India. Design:In Study 1, the Positive Eating Scale (PES) was tested and validated in a large longitudinal sample (T1:N = 772; T2:N = 510). In Study 2, the PES was tested in online samples from the USA, India and Germany (totalN = 749). Main Outcome Measures:Health risk status was measured in Study 1 with objective health parameters (fasting serum glucose, triglycerides, high-density lipoprotein cholesterol, blood pressure, waist circumference, BMI). Results:Study 1 revealed acceptable psychometric properties of the PES, internal consistency (α = .87), as well as test–retest reliability after six months (r = .67). Importantly, a positive relationship with eating was associated with decreased health risk factors six months later. In Study 2, the structure of the PES was confirmed for German, Indian and US-American adults, suggesting validity across remarkably different eating environments. Conclusion:A positive relationship with eating might be a fruitful starting point for prevention and intervention programmes promoting physical and psychological health. [ABSTRACT FROM AUTHOR]

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Renal tubular sodium (Na) handling plays a key role in blood pressure (BP) regulation. Several cross-sectional studies reported a positive association between higher proximal tubule fractional reabsorption of Na and BP, but no prospective investigation has been reported of this possible association. Hence, the purpose of this study was to estimate the predictive role of renal Na handling on the risk of incident hypertension and the changes in BP occurring in the 8-year follow-up observation of a sample of initially normotensive men (The Olivetti Heart Study). The study included 294 untreated normotensive non-diabetic men with normal renal function examined twice (1994–95 and 2002–04). Renal tubular Na handling was estimated by exogenous lithium clearance. Fractional reabsorption of Na in proximal and distal tubules was calculated and included in the analysis. At baseline, there was no association between BP and either proximal or distal fractional reabsorption of Na. At the end of the 8-year follow-up, direct associations were observed between baseline proximal (but not distal) Na fractional reabsorption and the changes occurred in systolic and diastolic BP over time (+2.79 and +1.53 mmHg, respectively, per 1SD difference in proximal Na-FR; p<0.01). Also multivariable analysis showed a direct association between baseline proximal Na fractional reabsorption and risk of incident hypertension, independently of potential confounders (OR: 1.34, 95%CI:1.06–1.70). The results of this prospective investigation strongly suggest a causal relationship between an enhanced rate of Na reabsorption in the proximal tubule and the risk of incident hypertension in initially normotensive men. [ABSTRACT FROM AUTHOR]

Sodium plays an important pathophysiological role in blood pressure (BP) values and in the development of hypertension, and epidemiological studies such as the Intersalt Study have shown that the increase in BP occurring with age is determined by salt intake. Recently, a meta-analysis of 13 prospective studies has also shown the close relationship between excess sodium intake and higher risk of stroke and total cardiovascular events. However, the BP response to changing salt intake displayed a marked variability, as first suggested by Kawasaki et al. (The effect of high-sodium and low-sodium intakes on blood pressure and other related variables in human subjects with idiopathic hypertension. Am J Med 1978; 64: 193-198) and later by Weinberger et al. (Definitions and characteristics of sodium sensitivity and blood pressure resistance. Hypertension 1986; 8: II127-II134), who recognized the heterogeneity of the BP response to salt and developed the concept of salt sensitivity. We have a large body of evidence in favour of a major role of metabolic and neuro-hormonal factors in determining BP salt sensitivity in association with the effect of genetic variation. There is evidence that salt sensitivity influences the development of organ damage, even independently--at least in part--of BP levels and the occurrence of hypertension. In addition, several observational studies indicate that salt sensitivity is clearly associated with a higher rate of cardiovascular events and mortality, independently of BP levels and hypertension. A cluster of factors with well-known atherogenic potential such as hyperinsulinaemia, dyslipidaemia and microalbuminuria--all known to be prevalent in salt-sensitive hypertension--might at least partially explain the increased cardiovascular risk observed in salt sensitive individuals. The gold standard for the evaluation of BP salt sensitivity is the BP response to a moderate reduction of salt intake for several weeks; nevertheless, these protocols often suffer of poor patient compliance to dietary instructions. To overcome this problem, short-term tests have been proposed that evaluate either large differences in salt intake for a few days or the response to intravenous administration of saline solution and short-acting diuretics. Recently, the use of ambulatory BP measurement has been proposed for the clinical assessment of BP salt sensitivity. Noteworthy, BP salt sensitivity, in whomever or however assessed, behaves as a continuous variable but salt sensitivity is used as a categorical parameter, with salt-sensitive individuals being defined as those with a difference in BP between low- and high-sodium intake >10%, and salt-resistant subjects those in whom BP does not increase or shows an increase <5% under sodium loading. The general conclusion that can and should be drawn from the above considerations is that the paradigm of salt sensitivity, despite its important pathophysiological meaning, is not helpful, so far, to the practising physician in clinical practice nor is it relevant or useful to the design and implementation of a population-based strategy of salt intake reduction; however, further studies are warranted for an accurate assessment of the salt-sensitivity phenotype in clinical practice. In the absence of a population strategy for salt intake reduction, the aim should be the generation of a 'low sodium environment' allowing for a dietary salt intake tailored on true human requirements and not on deleterious lifestyle habits. [ABSTRACT FROM AUTHOR]

In a population with high sodium consumption, we assessed relation between brachial and central blood pressures, elastic properties of large arteries, echocardiographic left ventricular diastolic function and sodium reabsorption as fractional urinary lithium excretion in proximal (FELi) and fractional sodium reabsorption in distal tubules assessed using the endogenous lithium clearance. Mean±s.d. age of 131 treated hypertensive patients (66 men and 65 women) was 61.9±7.5 years. We found significant interaction between left ventricular diastolic function and FELi with respect to the values of brachial blood pressure: systolic (SBP), diastolic (DBP) and mean blood pressure (MBP) (all PINT<0.03). In patients with FELi below the median value and impaired left ventricular diastolic function, the values of SBP (149.3 vs 132.5 mm Hg; P=0.005), DBP (85.1 vs 76.1 mm Hg; P=0.001), MBP (106.5 vs 94.9 mm Hg; P=0.001), central SBP (SBPC) (137.4 vs 122.0 mm Hg; P=0.01), central DBP (DBPC) (84.8 vs 76.0 mm Hg; P=0.003), central MBP (MBPC) (106.9 vs 95.9 mm Hg; P=0.007), aortic pulse wave augmentation (18.0 vs 13.5 mm Hg; P=0.03), pulse wave velocity (14.6 vs 12.5 m s−1; P=0.02) and central aortic pulse wave augmentation index (155.7% vs 140.9%; P=0.01) were significantly higher than in patients with normal left ventricular diastolic function. Such relationships were not observed in the entire group and patients with FELi above the median value. In the hypertensive population with high sodium intake, increased sodium reabsorption in proximal tubules may affect blood pressure parameters and arterial wall damage, thus contributing to the development of left ventricular diastolic function impairment. [ABSTRACT FROM AUTHOR]

Hypertension remains an important cause of morbidity and mortality in patients with chronic kidney disease. It both contributes to and is a consequence of chronic renal dysfunction. There is a high prevalence of hypertension in chronic kidney disease, and rates of control remain sub-optimal. Numerous studies have highlighted the benefit of treating hypertension in reducing the overall mortality as well as progression of renal disease in this population. Non-pharmacologic treatment strategies remain the primary intervention in all patients but are insufficient on their own to control hypertension in most cases. Pharmacologic treatment recommendations, however, vary depending on the specific etiology of disease as well as patient characteristics. Though most classes of anti-hypertensive drugs can be used to lower blood pressure in chronic kidney disease, therapy needs to be selected based on the presence of specific co-morbidities as well as the etiology of the kidney disease. Most patients will require multi-drug therapy for achieving target blood pressure goals. This review discusses the pharmacologic options in management of hypertension in various forms of chronic kidney disease. [ABSTRACT FROM AUTHOR]

BACKGROUND Although groups of African descent are particularly sensitive to blood pressure (BP) effects of salt intake, the role of obesity and insulin resistance in mediating this effect is uncertain. We determined whether obesity or insulin resistance is independently associated with urinary Na+/K+–BP relationships in a community sample of African ancestry. METHODS We measured 24-hour urinary Na+/K+, homeostasis model assessment of insulin resistance (HOMA-IR), and nurse-derived conventional and 24-hour ambulatory BP in 331 participants from a South African community sample of black African descent not receiving treatment for hypertension. RESULTS With adjustments for diabetes mellitus and the individual terms, an interaction between waist circumference and urinary Na+/K+ was associated with day diastolic BP (P < 0.05) and an interaction between log HOMA-IR and urinary Na+/K+ was associated with 24-hour and day systolic (P < 0.05) and 24-hour, day, and night diastolic (P < 0.002; P < 0.001) BP. The multivariable-adjusted relationship between urinary Na+/K+ and night diastolic BP increased across tertiles of HOMA-IR (tertile 1: β-coefficient = −0.79±0.47; tertile 2: β-coefficient = 0.65±0.35; tertile 3: β-coefficient = 1.03±0.46; P < 0.05 tertiles 3 and 2 vs. 1). The partial correlation coefficients for relationships between urinary Na+/K+ and 24-hour (partial r = 0.19; P < 0.02), day (partial r = 0.17; P < 0.05), and night (partial r = 0.18; P < 0.02) diastolic BP in participants with log HOMA-IR greater than or equal to the median were greater than those for relationships between urinary Na+/K+ and 24-hour (partial r = −0.08; P = 0.29), day (partial r = −0.10; P < 0.22), and night (partial r = −0.06; P = 0.40) diastolic BP in participants with log HOMA-IR less than the median (comparisons of r values: P < 0.05). CONCLUSIONS Insulin resistance may modify the relationship between salt intake, indexed by urinary Na+/K+, and ambulatory BP in groups of African descent. [ABSTRACT FROM AUTHOR]

Obesity is a risk factor for type 2 diabetes mellitus (DM) and is associated with chronic kidney disease. Activation of the renin-angiotensin-aldosterone system (RAAS) is common in obesity. The RAAS is an important mediator of hypertension. Mechanisms involved in activation of the RAAS in obesity include sympathetic stimulation, synthesis of adipokines in the RAAS by visceral fat, and hemodynamic alterations. The RAAS is known for its role in regulating blood pressure and fluid and electrolyte homeostasis. The role of local/tissue RAAS in specific tissues has been a focus of research. Urinary angiotensinogen (UAGT) provides a specific index of the intrarenal RAAS. Investigators have demonstrated that sex steroids can modulate the expression and activity of the different components of the intrarenal RAAS and other tissues. Our data suggest that obese women without DM and hypertension have significantly higher levels of UAGT than their male counterparts. These differences existed without any background difference in the ratio of microalbumin to creatinine in the urine or the estimated glomerular filtration rate, raising a question about the importance of baseline gender differences in the endogenous RAAS in the clinical spectrum of cardiovascular diseases and the potential utility of UAGT as a marker of the intrarenal RAAS. Animal studies have demonstrated that modifying the amount of angiotensin, the biologically active component of the RAAS, directly influences body weight and adiposity. This article reviews the role of the RAAS in renal injury seen in obesity and the metabolic syndrome. [ABSTRACT FROM AUTHOR]

Background. Recent experimental findings demonstrate vascular endothelial growth factor C (VEGF-C)-mediated water-free storage of salt in the interstitium, which prevents a salt-sensitive blood pressure state. It is unknown whether this mechanism plays a role in salt homeostasis and regulation of blood pressure in humans as well. Therefore, we investigated circulating VEGF-C levels and blood pressure during different well-controlled salt intake in chronic kidney disease (CKD) patients and in healthy subjects. Methods. In two crossover studies, non-diabetic proteinuric CKD patients (n = 32) and healthy subjects (n = 31) were treated with consecutively a low-sodium diet (LS, aim 50 mmol Na+/day) and a high-sodium diet (HS, aim 200 mmol Na+/day) in random order, during two 6-week (CKD patients) and two 1-week periods (healthy subjects). Results. We found that VEGF-C levels are higher during HS than during LS in CKD patients (P = 0.034) with a trend towards higher VEGF-C in healthy subjects as well (P = 0.070). In CKD patients, HS was associated with higher NT-proBNP levels (P = 0.005) and body weight (P = 0.013), consistent with extracellular volume (ECV) expansion and with higher blood pressure (P < 0.001), indicating salt sensitivity. In healthy subjects, blood pressure was not affected by dietary salt (P = 0.14), despite a rise in ECV (P = 0.023). Discussion. Our findings support a role for VEGF-C-mediated salt homeostasis in humans. Considering the salt sensitivity of blood pressure, this buffering mechanism appears to be insufficient in proteinuric CKD patients. Future studies are needed to provide causality and to substantiate the clinical and therapeutic relevance of this VEGF-C regulatory mechanism in humans. [ABSTRACT FROM PUBLISHER]

The aim of this study was to evaluate the arterial blood pressure and renal function of female rats in persistent estrus. Twenty-five female Wistar-Hannover rats were randomly divided into two groups: Group I (control, n = 15) and experimental (persistent estrus, n = 10). A tail-cuff system was used to measure blood pressure at 12 weeks of life. Parameters to evaluate renal function were taken into consideration. A significant increase in arterial pressure and a significant decrease in fractional sodium excretion were found in the androgenized animals compared to controls. There was no difference between the two groups with respect to glomerular filtration rate or in fractional potassium excretion. An increase in blood pressure and a reduction in fractional sodium excretion occur in female rats in persistent estrus. [ABSTRACT FROM AUTHOR]

WNK1 - a serine/threonine kinase involved in electrolyte homeostasis and blood pressure (BP) control - is an excellent candidate gene for essential hypertension (EH). We and others have previously reported association between WNK1 and BP variation. Using tag SNPs (tSNPs) that capture 100% of common WNK1 variation in HapMap, we aimed to replicate our findings with BP and to test for association with phenotypes relating to WNK1 function in the British Genetics of Hypertension (BRIGHT) study case-control resource (1700 hypertensive cases and 1700 normotensive controls). We found multiple variants to be associated with systolic blood pressure, SBP (7/28 tSNPs min-p = 0.0005), diastolic blood pressure, DBP (7/28 tSNPs min-p = 0.002) and 24 hour urinary potassium excretion (10/28 tSNPs min-p = 0.0004). Associations with SBP and urine potassium remained significant after correction for multiple testing (p= 0.02 and p = 0.01 respectively). The major allele (A) of rs765250, located in intron 1, demonstrated the strongest evidence for association with SBP, effect size 3.14 mmHg (95%CI:1.23-4.9), DBP 1.9 mmHg (95%CI:0.7-3.2) and hypertension, odds ratio (OR: 1.3 [95%CI: 1.0-1.7]).We genotyped this variant in six independent populations (n= 14,451) and replicated the association between rs765250 and SBP in a meta-analysis (p = 7×10-3, combined with BRIGHT data-set p = 2610-4, n = 17,851). The associations of WNK1 with DBP and EH were not confirmed. Haplotype analysis revealed striking associations with hypertension and BP variation (global permutation p<10-7). We identified several common haplotypes to be associated with increased BP and multiple low frequency haplotypes significantly associated with lower BP (>10 mmHg reduction) and risk for hypertension (OR<0.60). Our data indicates that multiple rare and common WNK1 variants contribute to BP variation and hypertension, and provide compelling evidence to initiate further genetic and functional studies to explore the role of WNK1 in BP regulation and EH. [ABSTRACT FROM AUTHOR]

This study tested the hypothesis that inducing hyperinsulinemia and hyperglycemia in dogs, by infusing glucose chronically intravenously, would increase tubular sodium reabsorption and cause hypertension. Glucose was infused for 6 days (14 mg·kg-1min-1 iv) in five uninephrectomized (UNX) dogs. Mean arterial pressure (MAP) and renal blood flow (RBF) were measured 18 h/day using DSI pressure units and Transonic flow probes, respectively. Urinary sodium excretion (UNaV) decreased significantly on day I and remained decreased over the 6 days, coupled with a significant, sustained increase in RBF, averaging ~20% above control on day 6. Glomerular filtration rate and plasma renin activity (PRA) also increased. However, although MAP tended to increase, this was not statistically significant. Therefore, the glucose infusion was repeated in six dogs with 70% surgical reduction in kidney mass (RKM) and high salt intake. Blood glucose and plasma insulin increased similar to the UNX dogs, and there was significant sodium retention, but MAP still did not increase. Interestingly, the increases in PRA and RBF were prevented in the RKM dogs. The decrease in UNaY, increased RBF, and slightly elevated MAP show that glucose infusion in dogs caused a sustained increase in tubular sodium reabsorption by a mechanism independent of pressure natriuresis. The accompanying increase in PRA, together with the failure of either RBF or PRA to increase in the RKIVI dogs, suggests the site of tubular reabsorption was before the macula densa. However, the volume retention and peripheral edema suggest that systemic vasodilation offsets any potential renal actions to increase MAP in this experimental model in dogs. [ABSTRACT FROM AUTHOR]

Background Serum uric acid levels in humans are influenced by diet, cellular breakdown, and renal elimination, and correlate with blood pressure, metabolic syndrome, diabetes, gout, and cardiovascular disease. Recent genome-wide association scans have found common genetic variants of SLC2A9 to be associated with increased serum urate level and gout. The SLC2A9 gene encodes a facilitative glucose transporter, and it has two splice variants that are highly expressed in the proximal nephron, a key site for urate handling in the kidney. We investigated whether SLC2A9 is a functional urate transporter that contributes to the longstanding association between urate and blood pressure in man. Methods and Findings We expressed both SLC2A9 splice variants in Xenopus laevis oocytes and found both isoforms mediate rapid urate fluxes at concentration ranges similar to physiological serum levels (200-500 lM). Because SLC2A9 is a known facilitative glucose transporter, we also tested whether glucose or fructose influenced urate transport. We found that urate is transported by SLC2A9 at rates 45- to 60-fold faster than glucose, and demonstrated that SLC2A9-mediated urate transport is facilitated by glucose and, to a lesser extent, fructose. In addition, transport is inhibited by the uricosuric benzbromarone in a dose-dependent manner (Ki = 27 μM). Furthermore, we found urate uptake was at least 2-fold greater in human embryonic kidney (HEK) cells overexpressing SLC2A9 splice variants than nontransfected kidney cells. To confirm that our findings were due to SLC2A9, and not another urate transporter, we showed that urate transport was diminished by SLC2A9-targeted siRNA in a second mammalian cell line. In a cohort of men we showed that genetic variants of SLC2A9 are associated with reduced urinary urate clearance, which fits with common variation at SLC2A9 leading to increased serum urate. We found no evidence of association with hypertension (odds ratio 0.98, 95% confidence interval [CI] 0.9 to 1.05, p . 0.33) by meta-analysis of an SLC2A9 variant in six case-control studies including 11,897 participants. In a separate meta-analysis of four population studies including 11,629 participants we found no association of SLC2A9 with systolic (effect size-0.12 mm Hg, 95% CI-0.68 to 0.43, p=0.664) or diastolic blood pressure (effect size -0.03 mm Hg, 95% CI -0.39 to 0.31, p = 0.82). Conclusions This study provides evidence that SLC2A9 splice variants act as high-capacity urate transporters and is one of the first functional characterisations of findings from genome-wide association scans. We did not find an association of the SLC2A9 gene with blood pressure in this study. Our findings suggest potential pathogenic mechanisms that could offer a new drug target for gout. [ABSTRACT FROM AUTHOR]

The article comments on the salty connection between metabolic syndrome and blood pressure. It was inferred that many pathophysiological factors, including genetic polymorphisms, were implicated in salt sensitivity of blood pressure. Further, reports have supported a role of insulin resistance in salt-sensitive hypertension not necessarily associated with overt hyperinsulinemia. Indeed, pharmacogenomic research may disclose useful strategies to treat the metabolic syndrome and its complications.

The article comments on a meta-analysis on salt-sensitivity of blood pressure. It states that the study compared the efficacy of different classes of antihypertensive agents in adult patients with salt-sensitive hypertension and without concomitant diseases, and mentions that main findings indicated a greater BP effect of the calcium antagonist-diuretic combination, whereas the calcium antagonist-metformin association was most effective in obese patients.

Hypertension is the leading risk factor for premature death worldwide. The identification of modifiable causes of hypertension remains an imperative task. We aimed to investigate associations between 79 proteins implicated in cardiovascular disease and longitudinal blood pressure (BP) changes in three Swedish prospective cohorts. In a discovery phase, we investigated associations between baseline circulating protein levels assessed with a proximity extension assay and BP stage progression at follow-up 5 years later among persons without BP-lowering drugs at baseline in two independent community-based cohorts from the Prospective Investigation of the Vasculature in Uppsala Seniors study (PIVUS) and the Uppsala Longitudinal Study of Adult Men (ULSAM). We used an independent cohort, the Malmö Diet and Cancer Study (MDC), for replication. The primary outcome of BP stage progression was defined as per the 2017 AHA/ACC (American Heart Association/ American College of Cardiology) Guideline BP categories. We also investigated associations of protein levels with changes in BP on a continuous scale, and meta-analyzed all three cohorts. Levels of renin were associated with BP stage progression with a 5% false discovery rate (FDR) in the ULSAM (n = 238) and PIVUS (n = 566) cohorts, but we could not replicate this association in the MDC cohort (n = 2659). The association in the discovery cohorts was modest, with an odds ratio for BP stage progression over 5 years of 1.33 (95% confidence interval 1.14 to 1.56) per standard deviation of baseline renin. In conclusion, we could not find any novel robust associations with longitudinal BP increase in a proximity extension assay-based proteomics investigation in three cohorts. [ABSTRACT FROM AUTHOR]