Long-term aircraft noise exposure and risk of hypertension in the Nurses' Health Studies.

BACKGROUND: Aircraft noise can affect populations living near airports. Chronic exposure to aircraft noise has been associated with cardiovascular disease, including hypertension. However, previous studies have been limited in their ability to characterize noise exposures over time and to adequately control for confounders. OBJECTIVES: The aim of this study was to examine the association between aircraft noise and incident hypertension in two cohorts of female nurses, using aircraft noise exposure estimates with high spatial resolution over a 20-year period. METHODS: We obtained contour maps of modeled aircraft noise levels over time for 90 U.S. airports and linked them with geocoded addresses of participants in the Nurses' Health Study (NHS) and Nurses' Health Study II (NHS II) to assign noise exposure for 1994-2014 and 1995-2013, respectively. We used time-varying Cox proportional hazards models to estimate hypertension risk associated with time-varying noise exposure (dichotomized at 45 and 55 dB(A)), adjusting for fixed and time-varying confounders. Results from both cohorts were pooled via random effects meta-analysis. RESULTS: In meta-analyses of parsimonious and fully-adjusted models with aircraft noise dichotomized at 45 dB(A), hazard ratios (HR) for hypertension incidence were 1.04 (95% CI: 1.00, 1.07) and 1.03 (95% CI: 0.99, 1.07), respectively. When dichotomized at 55 dB(A), HRs were 1.10 (95% CI: 1.01, 1.19) and 1.07 (95% CI: 0.98, 1.15), respectively. After conducting fully-adjusted sensitivity analyses limited to years in which particulate matter (PM) was obtained, we observed similar findings. In NHS, the PM-unadjusted HR was 1.01 (95% CI: 0.90, 1.14) and PM-adjusted HR was 1.01 (95% CI: 0.89, 1.14); in NHS II, the PM-unadjusted HR was 1.08 (95% CI: 0.96, 1.22) and the PM-adjusted HR was 1.08 (95% CI: 0.95, 1.21). Overall, in these cohorts, we found marginally suggestive evidence of a positive association between aircraft noise exposure and hypertension.

Postanesthesia ultrasound facilitates creation of more preferred accesses without affecting access survival.

OBJECTIVE: The results of preoperative ultrasound (pre-US) vein mapping for hemodialysis access creation can be affected by environmental and clinical factors, such as ambient temperature, acute illness, recent phlebotomy, and hypovolemia. These factors may inadvertently exclude otherwise viable veins as options for access creation. We hypothesized that repeating the ultrasound vein mapping immediately preoperatively after anesthesia administration (post-US) identifies additional veins not appreciated by pre-US, thereby altering the operative plan and producing more preferred accesses, particularly more forearm accesses. METHODS: We performed a retrospective cohort study of patients (N = 323) at one institution who underwent pre-US followed by creation of a permanent dialysis access (fistula or graft) between January 2008 and December 2013. By applying the Silva criteria to pre-US vein mapping reports, a preoperative surgical plan was established. There were 99 patients who underwent only pre-US (group I); an additional post-US was performed in 224 patients (group II). Using multivariable logistic regression, we tested the association of post-US (group II) with pre-US alone (group I) with a change in operative plan and placement of a more preferred access (ie, more distal and autogenous). We also analyzed access survival using multivariable Cox proportional hazards regression and determined maturation rates for accesses in groups I and II. RESULTS: In group II, there were more changes in operative plan after controlling for potential confounders (adjusted odds ratio, 1.96; 95% confidence interval, 1.18-3.25), and more preferred accesses were created (adjusted odds ratio, 1.82; 95% confidence interval, 1.01-3.27). In addition, more autogenous accesses were created in group II when initially only upper arm graft options had been identified (P = .01); overall, more forearm accesses were created in group II (P = .03). There was no significant difference in access maturation and patency in comparing accesses in group I and group II, despite creation of autogenous accesses in group II that are usually associated with higher rates of access failure. In fact, forearm radial-cephalic autogenous accesses created in group II had secondary patency rates of 91% at 2 years. CONCLUSIONS: Our study supports the hypothesis that the use of post-US in addition to pre-US leads to placement of more preferred accesses while maintaining maturation and patency rates. Ultrasound evaluation after anesthesia should be considered a step in the process of care for hemodialysis access creation to improve outcomes.

Diet-dependent acid load and type 2 diabetes: pooled results from three prospective cohort studies.

AIMS/HYPOTHESIS: Studies suggest a potential link between low-grade metabolic acidosis and type 2 diabetes. A western dietary pattern increases daily acid load but the association between diet-dependent acid load and type 2 diabetes is still unclear. This study aimed to assess whether diet-dependent acid load is associated with the risk of type 2 diabetes. METHODS: We examined the association between energy-adjusted net endogenous acid production (NEAP), potential renal acid load (PRAL) and animal protein-to-potassium ratio (A:P) on incident type 2 diabetes in 67,433 women from the Nurses' Health Study, 84,310 women from the Nurses' Health Study II and 35,743 men from the Health Professionals' Follow-up Study who were free from type 2 diabetes, cardiovascular disease and cancer at baseline. Study-specific HRs were estimated using Cox proportional hazards models with time-varying covariates and were pooled using a random effects meta-analysis. RESULTS: We documented 15,305 cases of type 2 diabetes during 4,025,131 person-years of follow-up. After adjustment for diabetes risk factors, dietary NEAP, PRAL and A:P were positively associated with type 2 diabetes (pooled HR [95% CI] for highest (Q5) vs lowest quintile (Q1): 1.29 [1.22, 1.37], p trend <0.0001; 1.29 [1.22, 1.36], p trend <0.0001 and 1.32 [1.24, 1.40], p trend <0.0001 for NEAP, PRAL and A:P, respectively). These results were not fully explained by other dietary factors including glycaemic load and dietary quality (HR [95% CI] for Q5 vs Q1: 1.21 [1.09, 1.33], p trend <0.0001; 1.19 [1.08, 1.30] and 1.26 [1.17, 1.36], p trend <0.0001 for NEAP, PRAL and A:P, respectively). CONCLUSIONS/INTERPRETATION: This study suggests that higher diet-dependent acid load is associated with an increased risk of type 2 diabetes. This association is not fully explained by diabetes risk factors and overall diet quality.

Hypertension, use of antihypertensive medications, and risk of epithelial ovarian cancer.

Few studies have examined the associations of hypertension and antihypertensive medications with ovarian cancer. In particular, beta-blockers, one of the most commonly prescribed medications to treat hypertension, may reduce ovarian cancer risk by inhibiting beta-adrenergic signaling. We prospectively followed 90,384 women in the Nurses' Health Study (NHS) between 1988-2012 and 113,121 NHSII participants between 1989-2011. Hypertension and use of antihypertensive medications were self-reported biennially. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). We documented 948 ovarian cancer cases during follow-up. Similar results were observed in the two cohorts. While hypertension was not associated with ovarian cancer risk (Pooled HR = 1.01; 95% CI = 0.88, 1.16), current use of any antihypertensive medication was associated with slightly increased risk compared to never users (Pooled HR = 1.18; 95% CI: 1.02, 1.37). This increased risk was primarily due to use of thiazide diuretics (Pooled HR = 1.37; 95% CI: 1.13, 1.68). No associations were observed for beta-blockers or angiotensin-converting-enzyme inhibitors. Calcium channel blockers (CCBs) were associated with suggestively reduced risk (NHS HR = 0.73; 95% CI: 0.53, 1.01), after adjusting for all antihypertensive medications. Associations were similar among hypertensive women and stronger for longer use of thiazide diuretics and CCBs. In conclusion, our results provided no evidence that beta-blockers were associated with reduced ovarian cancer risk. In contrast, we observed an increased risk for use of thiazide diuretics that should be confirmed in other studies.

Association of short sleep duration and rapid decline in renal function.

The kidney is influenced by circadian rhythms and is entrained to the sleep-wake cycle allowing anticipation of the metabolic and physiological demands of the kidney throughout a 24-hour cycle. Although sleep disruption has been studied extensively in cardiovascular and metabolic disease, its association with chronic kidney disease has not been shown. We examined this in a prospective cohort study of 4238 participants from the Nurses' Health Study and analyzed the association of self-reported sleep duration with decline in renal function over an 11-year period (1989 to 2000). Individuals who reported shorter sleep duration were more likely to experience a rapid decline in estimated glomerular filtration rate (30% or more). Compared with sleeping 7 to 8 hours per night, the adjusted odds ratios for a rapid decline in renal function were a significant 1.79 (95% CI, 1.06-3.03) for 5 hours or less sleep per night, a significant 1.31 (95% CI, 1.01-1.71) for 6 hours sleep per night, but an insignificant 0.88 (95% CI, 0.50-1.57) for 9 or more hours sleep per night. Similarly, there was a significant trend in the adjusted annualized decline in estimated glomerular filtration rate of 1.2 ml/min/1.73 m(2)/year, 0.9 ml/min/1.73 m(2)/year, 0.8 ml/min/1.73 m(2)/year, and 0.8 ml/min/1.73 m(2)/year for individuals sleeping 5 hours or less per night, 6 hours per night, 7 to 8 hours per night, and 9 hours or more per night, respectively. Thus, shorter sleep duration is prospectively and independently associated with faster decline in renal function.

Antihypertensive medication use and incident breast cancer in women.

The purpose of this study was to evaluate whether antihypertensive medication use, including long-term use, is associated with increased breast cancer incidence in women. We studied 210,641 U.S. registered nurses participating in the Nurses' Health Study (NHS) and Nurses' Health Study II (NHS II). Information on antihypertensive medication use was collected on biennial questionnaires in both cohorts, and breast cancer cases were ascertained during this period. Multivariable-adjusted Cox proportional hazard models were used to estimate relative risks of invasive breast cancer over follow-up (1988-2012 in NHS, 1989-2011 in NHS II) across categories of overall antihypertensive medication use and use of specific classes (diuretics, beta blockers, calcium channel blockers, and angiotensin-converting enzyme inhibitors). During follow-up, 10,012 cases of invasive breast cancer developed (6718 cases in NHS and 3294 in the NHS II). Overall, current use of any antihypertensive medication was not associated with breast cancer risk compared with past/never use in NHS (multivariable-adjusted relative risk = 1.00, 95 % CI = 0.95-1.06) or NHS II (multivariable-adjusted relative risk = 0.94, 95 % CI = 0.86-1.03). Furthermore, no specific class of antihypertensive medication was consistently associated with breast cancer risk. Results were similar when we considered hypertensive women only, and when we evaluated consistency and duration of medication use over time. Overall, antihypertensive medication use was largely unrelated to the risk of invasive breast cancer among women in the NHS cohorts.

Joint association between birth weight at term and later life adherence to a healthy lifestyle with risk of hypertension: a prospective cohort study.

BACKGROUND: Low birth weight and unhealthy lifestyles in adulthood have been independently associated with an elevated risk of hypertension. However, no study has examined the joint effects of these factors on incidence of hypertension. METHODS: We followed 52,114 women from the Nurses' Health Study II without hypercholesterolemia, diabetes, cardiovascular disease, cancer, prehypertension, and hypertension at baseline (1991-2011). Women born preterm, of a multiple pregnancy, or who were missing birth weight data were excluded. Unhealthy adulthood lifestyle was defined by compiling status scores of body mass index, physical activity, alcohol consumption, the Dietary Approaches to Stop Hypertension diet, and the use of non-narcotic analgesics. RESULTS: We documented 12,588 incident cases of hypertension during 20 years of follow-up. The risk of hypertension associated with a combination of low birth weight at term and unhealthy lifestyle factors (RR, 1.95; 95 % CI, 1.83-2.07) was more than the addition of the risk associated with each individual factor, indicating a significant interaction on an additive scale (P interaction <0.001). The proportions of the association attributable to lower term birth weight alone, unhealthy lifestyle alone, and their joint effect were 23.9 % (95 % CI, 16.6-31.2), 63.7 % (95 % CI, 60.4-66.9), and 12.5 % (95 % CI, 9.87-15.0), respectively. The population-attributable-risk for the combined adulthood unhealthy lifestyle and low birth weight at term was 66.3 % (95 % CI, 56.9-74.0). CONCLUSION: The majority of cases of hypertension could be prevented by the adoption of a healthier lifestyle, though some cases may depend on simultaneous improvement of both prenatal and postnatal factors.

Visit-to-visit variability in blood pressure and kidney and cardiovascular outcomes in patients with type 2 diabetes and nephropathy: a post hoc analysis from the RENAAL study and the Irbesartan Diabetic Nephropathy Trial.

BACKGROUND: Increased systolic blood pressure variability between outpatient visits is associated with increased incidence of cardiovascular end points. However, few studies have examined the association of visit-to-visit variability in systolic blood pressure with clinically relevant kidney disease outcomes. We analyzed the association of systolic blood pressure visit-to-visit variability with renal and cardiovascular morbidity and mortality among individuals with diabetes and nephropathy. STUDY DESIGN: Observational analysis of IDNT (Irbesartan Diabetic Nephropathy Trial) and the RENAAL (Reduction of End Points in Non-Insulin-Dependent Diabetes With the Angiotensin II Antagonist Losartan) Study. SETTING & PARTICIPANTS: 2,739 participants with type 2 diabetes and nephropathy with at least 1 year of blood pressure measurements available. PREDICTORS: Systolic blood pressure visit-to-visit variability was calculated from the SD of the systolic blood pressure from 4 visits occurring 3-12 months postrandomization. OUTCOMES: The kidney disease outcome was defined as time to confirmed doubling of serum creatinine level, end-stage renal disease, or death; the cardiovascular outcome was defined as time to cardiovascular death, myocardial infarction, stroke, hospitalization for heart failure, or revascularization. RESULTS: Mean visit-to-visit variability in systolic blood pressure from 3 to 12 months postrandomization was 12.0±6.8(SD)mmHg. Following this ascertainment period, there were 954 kidney disease and 542 cardiovascular events. Greater systolic blood pressure visit-to-visit variability was associated independently with increased risk of the composite kidney disease end point (HR per 1-SD increment, 1.08 [95%CI, 1.01-1.16]; P=0.02) and end-stage renal disease, but not with the cardiovascular outcome. LIMITATIONS: Observational study with the potential for confounding. CONCLUSIONS: In diabetic individuals with nephropathy, systolic blood pressure visit-to-visit variability is associated independently with hard kidney disease outcomes.

Association between sodium intake and change in uric acid, urine albumin excretion, and the risk of developing hypertension.

BACKGROUND: A high-sodium diet has little short-term effect on blood pressure in nonhypertensive individuals but, for unclear reasons, is associated with hypertension if consumed long term. We hypothesized that a chronically high sodium intake would be associated with increases in biomarkers of endothelial dysfunction, specifically serum uric acid (SUA) and urine albumin excretion (UAE), and that high sodium intake would be associated with incident hypertension among those with higher SUA and UAE. METHODS AND RESULTS: We prospectively analyzed the associations between sodium intake and the change in SUA (n=4062) and UAE (n=4146) among participants of the Prevention of Renal and Vascular End Stage Disease (PREVEND) study who were not taking antihypertensive medications. We also examined the association of sodium intake with the incidence of hypertension (n=5556) among nonhypertensive participants. After adjustment for confounders, each 1-g-higher sodium intake was associated with a 1.2-µmol/L increase in SUA (P=0.01) and a 4.6-mg/d increase in UAE (P<0.001). The relation between sodium intake and incident hypertension varied according to SUA and UAE. For each 1-g-higher sodium intake, the adjusted hazard ratio for developing hypertension was 0.98 (95% confidence interval, 0.89-1.08) among those in the lowest tertile of SUA and 1.09 (1.02-1.16) among those in the highest tertile. Corresponding hazard ratios were 0.99 (confidence interval, 0.93-1.06) among participants whose UAE was <10 mg/d and 1.18 (confidence interval, 1.07-1.29) among those whose UAE was >15 mg/d. CONCLUSIONS: Over time, higher sodium intake is associated with increases in SUA and UAE. Among individuals with higher SUA and urine UAE, a higher sodium intake is an independent risk factor for developing hypertension.

Association of nocturnal melatonin secretion with insulin resistance in nondiabetic young women.

Exogenous melatonin ameliorates insulin resistance in animals, while among humans, polymorphisms in the melatonin receptor gene are associated with insulin resistance. We aimed to investigate the association of endogenous nocturnal melatonin secretion with insulin resistance in humans. We analyzed the association between endogenous nocturnal melatonin secretion, estimated by measuring the main melatonin metabolite, 6-sulfatoxymelatonin, from the first morning urinary void, and the prevalence of insulin resistance based on fasting blood samples collected in a cross-sectional study of 1,075 US women (1997-1999) without diabetes, hypertension, or malignancy. Urinary 6-sulfatoxymelatonin level was standardized to urinary creatinine level; insulin resistance was defined as an insulin sensitivity index value (using the McAuley formula) less than 7.85. Logistic regression models included adjustment for age, body mass index, smoking, physical activity, alcohol intake, dietary glycemic index, family history of diabetes mellitus, blood pressure, plasma total cholesterol, uric acid, and estimated glomerular filtration rate. Higher nocturnal melatonin secretion was inversely associated with insulin levels and insulin resistance. In fully adjusted models, the odds ratio for insulin resistance was 0.45 (95% confidence interval: 0.28, 0.74) among women in the highest quartile of urinary 6-sulfatoxymelatonin:creatinine ratio compared with women in the lowest quartile. Nocturnal melatonin secretion is independently and inversely associated with insulin resistance.

Melatonin secretion and the incidence of type 2 diabetes.

IMPORTANCE: Loss-of-function mutations in the melatonin receptor are associated with insulin resistance and type 2 diabetes. Additionally, in a cross-sectional analysis of persons without diabetes, lower nocturnal melatonin secretion was associated with increased insulin resistance. OBJECTIVE: To study the association between melatonin secretion and the risk of developing type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS: Case-control study nested within the Nurses' Health Study cohort. Among participants without diabetes who provided urine and blood samples at baseline in 2000, we identified 370 women who developed type 2 diabetes from 2000-2012 and matched 370 controls using risk-set sampling. MAIN OUTCOME MEASURES: Associations between melatonin secretion at baseline and incidence of type 2 diabetes were evaluated with multivariable conditional logistic regression controlling for demographic characteristics, lifestyle habits, measures of sleep quality, and biomarkers of inflammation and endothelial dysfunction. RESULTS: The median urinary ratios of 6-sulfatoxymelatonin to creatinine were 28.2 ng/mg (5%-95% range, 5.5-84.2 ng/mg) among cases and 36.3 ng/mg (5%-95% range, 6.9-110.8 ng/mg) among controls. Women with lower ratios of 6-sulfatoxymelatonin to creatinine had increased risk of diabetes (multivariable odds ratio, 1.48 [95% CI, 1.11-1.98] per unit decrease in the estimated log ratio of 6-sulfatoxymelatonin to creatinine). Compared with women in the highest ratio category of 6-sulfatoxymelatonin to creatinine, those in the lowest category had a multivariable odds ratio of 2.17 (95% CI, 1.18-3.98) of developing type 2 diabetes. Women in the highest category of melatonin secretion had an estimated diabetes incidence rate of 4.27 cases/1000 person-years compared with 9.27 cases/1000 person-years in the lowest category. CONCLUSIONS AND RELEVANCE: Lower melatonin secretion was independently associated with a higher risk of developing type 2 diabetes. Further research is warranted to assess if melatonin secretion is a modifiable risk factor for diabetes within the general population.

Associations between long-term aircraft noise exposure, cardiovascular disease, and mortality in US cohorts of female nurses.

There is limited research examining aircraft noise and cardiovascular disease (CVD) risk. The objective of this study was to investigate associations of aircraft noise with CVD among two US cohorts, the Nurses' Health Study (NHS) and Nurses' Health Study II (NHSII). Methods: Between 1994 and 2014, we followed 57,306 NHS and 60,058 NHSII participants surrounding 90 airports. Aircraft noise was modeled above 44 A-weighted decibels (dB(A)) and linked to geocoded addresses. Based on exposure distributions, we dichotomized exposures at 50 dB(A) and tested sensitivity of this cut-point by analyzing aircraft noise as categories (<45, 45-49, 50-54, ≥55) and continuously. We fit cohort-specific Cox proportional hazards models to estimate relationships between time-varying day-night average sound level (DNL) and CVD incidence and CVD and all-cause mortality, adjusting for fixed and time-varying individual- and area-level covariates. Results were pooled using random effects meta-analysis. Results: Over 20 years of follow-up, there were 4529 CVD cases and 14,930 deaths. Approximately 7% (n = 317) of CVD cases were exposed to DNL ≥50 dB(A). In pooled analyses comparing ≥50 with <50 dB(A), the adjusted hazard ratio for CVD incidence was 1.00 (95% confidence interval: 0.89, 1.12). The corresponding adjusted hazard ratio for all-cause mortality was 1.02 (95% confidence interval: 0.96, 1.09). Patterns were similar for CVD mortality in NHS yet underpowered. Conclusions: Among participants in the NHS and NHSII prospective cohorts who generally experience low exposure to aircraft noise, we did not find adverse associations of aircraft noise with CVD incidence, CVD mortality, or all-cause mortality.

You are what you eat: dietary salt intake and renin-angiotensin blockade in diabetic nephropathy.

Interactions between sodium intake, the renin-angiotensin system, and renal and cardiovascular outcomes are incompletely understood. The analysis by Lambers Heerspink et al. shows that angiotensin receptor blockade improves diabetic nephropathy and cardiovascular disease more when dietary sodium intake is low, and suggests possible harm when sodium intake is high. These findings highlight dietary salt as a modifiable cardiovascular and renal risk factor and emphasize the need for detailed mechanistic studies.

Vitamin D and vascular disease: the current and future status of vitamin D therapy in hypertension and kidney disease.

Over the past decade, vitamin D has generated considerable interest as potentially having important effects on the vasculature and the kidney. Animal and human data indicate that vitamin D suppresses the activity of the renin-angiotensin system and improves endothelial function. Observational studies in humans suggest that low 25-hydroxyvitamin D (25[OH]D) levels are associated with a higher risk of hypertension. However, findings from randomized trials of vitamin D supplementation (with cholecalciferol or ergocalciferol) to lower blood pressure are inconsistent, possibly stemming from variability in study population, sample size, vitamin D dose, and duration. Supplementation with activated vitamin D (i.e., 1,25-dihydroxyvitamin D or analogues) in patients with chronic kidney disease reduces urine albumin excretion, an important biomarker for future decline in renal function. These studies are reviewed, with special emphasis on recent findings. Definitive studies are warranted to elucidate the effects of vitamin D supplementation on mechanisms of hypertension and kidney disease.

Sleep Restriction and Recurrent Circadian Disruption Differentially Affects Blood Pressure, Sodium Retention, and Aldosterone Secretion.

Prolonged exposure to chronic sleep restriction (CSR) and shiftwork are both associated with incident hypertension and cardiovascular disease. We hypothesized that the combination of CSR and shiftwork's rotating sleep schedule (causing recurrent circadian disruption, RCD) would increase blood pressure, renal sodium retention, potassium excretion, and aldosterone excretion. Seventeen healthy participants were studied during a 32-day inpatient protocol that included 20-h "days" with associated scheduled sleep/wake and eating behaviors. Participants were randomly assigned to restricted (1:3.3 sleep:wake, CSR group) or standard (1:2 sleep:wake, Control group) ratios of sleep:wake duration. Systolic blood pressure during circadian misalignment was ∼6% higher in CSR conditions. Renal sodium and potassium excretion showed robust circadian patterns; potassium excretion also displayed some influence of the scheduled behaviors (sleep/wake, fasting during sleep so made parallel fasting/feeding). In contrast, the timing of renal aldosterone excretion was affected predominately by scheduled behaviors. Per 20-h "day," total sodium excretion increased, and total potassium excretion decreased during RCD without a change in total aldosterone excretion. Lastly, a reduced total renal sodium excretion was found despite constant oral sodium consumption and total aldosterone excretion, suggesting a positive total body sodium balance independent of aldosterone excretion. These findings may provide mechanistic insight into the observed adverse cardiovascular and renal effects of shiftwork.

The Fok1 vitamin D receptor gene polymorphism is associated with plasma renin activity in Caucasians.

OBJECTIVES: 25-Hydroxyvitamin D (25(OH)D) deficiency and excess activity of the renin-angiotensin system (RAS) are both associated with cardiovascular disease. Vitamin D interacts with the vitamin D receptor (VDR) to negatively regulate renin expression in mice; however, human studies linking genetic variation in the VDR with renin are lacking. We evaluated (i) whether genetic variation in the VDR at the Fok1 polymorphism was associated with plasma renin activity (PRA) in a population of hypertensives and a separate population of normotensives and (ii) whether the association between Fok1 genotype and PRA was independent of 25(OH)D levels. DESIGN/PATIENTS/MEASUREMENTS: Genetic association study, assuming an additive model of inheritance, of 375 hypertensive and 146 normotensive individuals from the HyperPATH cohort, who had PRA assessments after 1 week of high dietary sodium balance (HS) and l week of low dietary sodium balance (LS). RESULTS: The minor allele (T) at the Fok1 polymorphism was significantly associated with lower PRA in hypertensives (LS: ß = -0·22, P < 0·01; HS: ß = -0·19, P < 0·01); when repeated in normotensives, a similar relationship was observed (LS: ß = -0·17, P < 0·05; HS: ß = -0·18, P = 0·14). In multivariable analyses, both higher 25(OH)D levels and the T allele at Fok1 were independently associated with lower PRA in hypertensives; however, 25(OH)D was not associated with PRA in normotensives. CONCLUSIONS: Genetic variation at the Fok1 polymorphism of the VDR gene, in combination with 25(OH)D levels, was associated with PRA in hypertension. These findings support the vitamin D-VDR complex as a potential regulator of renin activity in humans.

The association of plasma resistin with dietary sodium manipulation, the renin-angiotensin-aldosterone system, and 25-hydroxyvitamin D3 in human hypertension.

OBJECTIVE: Both resistin and vitamin D have been associated with the renin-angiotensin-aldosterone system (RAAS). We investigated the association between resistin and the RAAS, and resistin and vitamin D under controlled dietary sodium conditions. DESIGN: Retrospective cross-sectional study of subjects from the HyperPATH Consortium, who were maintained in high dietary sodium (HS) and low dietary sodium (LS) balance for 1 week each. PATIENTS: Caucasian subjects with hypertension (n=177). MEASUREMENTS: 25-Hydroxyvitamin D (25[OH]D) levels were used to assess vitamin D status. Plasma resistin and RAAS measures were evaluated on each dietary intervention. RESULTS: Resistin levels were significantly higher in LS, where RAAS activity was high, when compared with HS balance, where RAAS activity was suppressed (6.36 vs 5.86 µg/l, P < 0.0001); however, resistin concentrations were not associated with plasma renin activity or serum aldosterone on either diet. 25(OH)D levels were positively and independently associated with resistin in both dietary conditions (HS: ß=0.400, P-trend=0.027; LS: ß=0.540, P-trend=0.014). CONCLUSIONS: Dietary sodium loading reduced resistin levels, possibly by suppressing the RAAS; however, circulating RAAS components were not related to resistin concentrations within each specific dietary sodium condition. 25(OH)D was positively associated with resistin and may be involved in resistin regulation through an unknown mechanism. Further studies to understand resistin regulation in human hypertension better are warranted.

Primary care management of chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) causes substantial morbidity and mortality; however, there are limited data to comprehensively assess quality of care in this area. OBJECTIVE: To assess quality of care for CKD according to patient risk and identify correlates of improved care delivery. DESIGN: Retrospective cohort. SETTING: Fifteen health centers within a multi-site group practice in eastern Massachusetts. PARTICIPANTS: 166 primary care physicians caring for 11,774 patients with stages 3 or 4 CKD defined as two estimated glomerular filtration rates (eGFR) between 15 and 60. MAIN MEASURES: Two measures of kidney disease monitoring, five measures of cardiovascular disease management, four measures of metabolic bone disease and anemia management, and one measure of drug safety were extracted from the electronic health record. Primary care recognition of CKD was assessed as a problem list diagnosis, and nephrology co-management was assessed as at least one visit with a nephrologist in the prior 12 months. KEY RESULTS: Overall, 46% of patients were high risk for death based on the presence of diabetes, proteinuria, or an eGFR <45. Seventy percent of patients lacked annual urine protein testing, 46% had a blood pressure ≥130/80 mmHg and 25% were not receiving appropriate angiotensin blockade. Appropriate screening for anemia was common (76%), while screening rates for metabolic bone disease were low. Use of potentially harmful drugs was common (26%). Primary care physician recognition and nephrology co-management were both associated with improved quality of care, though rates of both were low (24% and 10%, respectively). CONCLUSIONS: Significant deficiencies in the quality of CKD care exist. Opportunities for improvement include increasing physician recognition of CKD and improving collaborative care with nephrology.

Lyme disease-associated glomerulonephritis.

We report two cases of Lyme disease-associated glomerulonephritis. A 57-year-old female presented with rash, volume overload, hypertension and rapidly progressive glomerulonephritis. Biopsy confirmed an immune complex-mediated, membranoproliferative lesion. She was treated successfully with steroids and antibiotics. In a second case, a 40-year-old male, with a previously known microscopic hematuria, presented with rash, arthralgias, new proteinuria and gross hematuria following a tick bite. Biopsy revealed focal proliferative IgA nephropathy. Treatment with steroids and antibiotics resulted in rapid resolution of findings. Acute Lyme disease may contribute to the development of de novo, or activation of previously quiescent, immune-mediated glomerular disease.

Plasma resistin levels associate with risk for hypertension among nondiabetic women.

Emerging evidence suggests a role for resistin in inflammation and vascular dysfunction, which may contribute to the pathogenesis of hypertension, but the association between resistin levels and incident hypertension is unknown. We examined the association between plasma resistin levels and the risk for incident hypertension among 872 women without a history of hypertension or diabetes from the Nurses' Health Study. We identified 361 incident cases of hypertension during 14 years of follow-up. After adjustment for potential confounders, resistin levels in the highest tertile conferred a 75% higher risk for hypertension than the lowest tertile (relative risk [RR] 1.75; 95% confidence interval [CI] 1.19 to 2.56). Further adjustment for other adipokines did not change the RR substantially. In stratified analysis, resistin levels in the highest tertile significantly increased the risk for hypertension among women aged >or=55 years (adjusted RR 2.40; 95% CI 1.55 to 3.73) but not among women aged <55 years (adjusted RR 0.64; 95% CI 0.25 to 1.62). In a subset analysis of 362 women who also had measurements of inflammatory and endothelial biomarkers, plasma resistin levels significantly correlated with IL-6, soluble TNF receptor 2, intercellular adhesion molecule 1, vascular adhesion molecule 1, and E-selectin after controlling for age and body mass index. After further adjustment for these biomarkers and C-reactive protein, resistin levels remained significantly associated with incident hypertension. In conclusion, higher plasma resistin levels independently associate with an increased risk for incident hypertension among women without diabetes.