Hypertension in the United States, 1999 to 2012: progress toward Healthy People 2020 goals.

BACKGROUND: To reduce the cardiovascular disease burden, Healthy People 2020 established US hypertension goals for adults to (1) decrease the prevalence to 26.9% and (2) raise treatment to 69.5% and control to 61.2%, which requires controlling 88.1% on treatment. METHODS AND RESULTS: To assess the current status and progress toward these Healthy People 2020 goals, time trends in National Health and Nutrition Examination Surveys 1999 to 2012 data in 2-year blocks were assessed in adults ≥18 years of age age-adjusted to US 2010. From 1999 to 2000 to 2011 to 2012, prevalent hypertension was unchanged (30.1% versus 30.8%, P=0.32). Hypertension treatment (59.8% versus 74.7%, P<0.001) and proportion of treated adults controlled (53.3%-68.9%, P=0.0015) increased. Hypertension control to <140/<90 mm Hg rose every 2 years from 1999 to 2000 to 2009 to 2010 (32.2% versus 53.8%, P<0.001) before declining to 51.2% in 2011 to 2012. Modifiable factor(s) significant in multivariable logistic regression modeling include: (1) increasing body mass index with prevalent hypertension (odds ratio [OR], 1.44); (2) lack of health insurance (OR, 1.68) and <2 healthcare visits per year (OR, 4.24) with untreated hypertension; (3) healthcare insurance (OR, 1.69), ≥2 healthcare visits per year (OR, 3.23), and cholesterol treatment (OR, 1.90) with controlled hypertension. CONCLUSIONS: The National Health and Nutrition Examination Survey 1999 to 2012 analysis suggests that Healthy People 2020 goals for hypertension ([1] prevalence shows no progress, [2] treatment was exceeded, and [3] control) have flattened below target. Findings are consistent with evidence that (1) obesity prevention and treatment could reduce prevalent hypertension, and (2) healthcare insurance, ≥2 healthcare visits per year, and guideline-based cholesterol treatment could improve hypertension control.

Selective cyclooxygenase-2 inhibitor suppresses renal thromboxane production but not proliferative lesions in the MRL/lpr murine model of lupus nephritis.

INTRODUCTION: Proliferative lupus nephritis (LN) is marked by increased renal thromboxane (TX) A2 production. Targeting the TXA2 receptor or TXA2 synthase effectively improves renal function in humans with LN and improves glomerular pathology in murine LN. This study was designed to address the following hypotheses: (1) TXA2 production in the MRL/MpJ-Tnfrsf6(lpr)/J (MRL/lpr) model of proliferative LN is cyclooxygenase (COX)-2 dependent and (2) COX2 inhibitor therapy improves glomerular filtration rate (GFR), proteinuria, markers of innate immune response and glomerular pathology. METHODS: Twenty female MRL/lpr and 20 BALB/cJ mice were divided into 2 equal treatment groups: (1) SC-236, a moderately selective COX2 inhibitor or (2) vehicle. After treatment from the age of 10 to 20 weeks, the effectiveness of inhibition of TXA2 was determined by measuring urine TXB2. Response endpoints measured at the age of 20 weeks were renal function (GFR), proteinuria, urine nitrate + nitrite (NO(x)) and glomerular histopathology. RESULTS: SC-236 therapy reduced surrogate markers of renal TXA2 production during early, active glomerulonephritis. When this pharmacodynamic endpoint was reached, therapy improved GFR. Parallel reductions in markers of the innate immune response (urine NO(x)) during therapy were observed. However, the beneficial effect of SC-236 therapy on GFR was only transient, and renal histopathology was not improved in late disease. CONCLUSIONS: These data demonstrate that renal TXA2 production is COX2 dependent in murine LN and suggest that NO production is directly or indirectly COX2 dependent. However, COX2 inhibitor therapy in this model failed to improve renal pathology, making COX2 inhibition a less attractive approach for treating LN.

Geographical patterns of end-stage renal disease incidence and risk factors in rural and urban areas of South Carolina.

To assess the geographical patterns of end-stage renal disease (ESRD) incidence and to identify the risk factors on the regional differences, the authors conducted an ecological study on incidence of ESRD and related risk factors in the 46 counties of South Carolina (SC). Age and gender adjusted, race specific incidence rates for each county in SC were calculated for the 11,346 ESRD patients of all ages who registered in the United States Renal Data Systems Network 6 from 1990 to 1999. County level exposure measures on population physician density, hospitalization rates of diabetes and hypertension, per capita income, percent college degree, and percent below poverty were evaluated. There was a significant increase in mean incidence rates of ESRD from 1990 to 1999 in SC (p<0.0001). The incidence rates were consistently higher in rural than in urban counties. Population physician density (relative risk (RR) 0.49, 95% confidence interval (95%Cl, 0.41-0.58) and rural residence (adjusted RR 1.66, 95%Cl 1.59-1.74) were significantly associated with ESRD incidence. The strong relationship between ESRD and physician density suggests that access to adequate treatment of diabetes and hypertension is of paramount importance for ESRD prevention, and has important public policy implications.

Glomerular filtration rate can be accurately predicted using lean mass measured by dual-energy X-ray absorptiometry.

BACKGROUND: Accurate assessment of renal function is important in the management of patients with kidney disease yet is often difficult to obtain. Formulae, designed for clinical use, have been developed to predict glomerular filtration rate (GFR) utilizing serum creatinine (Scr). Additional parameters are included in these formulae to account for variations in Scr due to differences in total body lean mass in kg (LM). Therefore, the purpose of this study was to derive a simple formula to predict GFR based on Scr and direct quantification of LM. METHODS: Ten subjects with a wide range of renal function had GFRs determined by [125I]iothalamate clearance and LM determined by dual-energy X-ray absorptiometry as well as fasting measurements of Scr, serum and 24 h urine urea nitrogen, and albumin. RESULTS: The following formula was derived using LM (kg) and Scr (mg/dl): predicted GFR=(2.4xLM)-(0.75xLMxScr). The correlation coefficient for this formula was 0.97, when compared with [125I]iothalamate clearances, and similar to the MDRD formulae (R=0.87-0.95). CONCLUSION: Although further validation is necessary, these findings suggest that total body non-invasive measurement of LM along with Scr can be used to accurately predict GFR.

Ethnic differences in blood pressure control among men at Veterans Affairs clinics and other health care sites.

BACKGROUND: Differential access to health care may contribute to lower blood pressure (BP) control rates to under 140/90 mm Hg in African American compared with white hypertensive patients, especially men (26.5% vs 36.5% of all hypertensive patients in the National Health and Nutrition Examination Survey 1999-2000). The Department of Veterans Affairs (VA) system, which provides access to health care and medications across ethnic and economic boundaries, may reduce disparities in BP control. METHODS: To test this hypothesis, BP treatment and control groups were compared between African American (VA, n = 4379; non-VA, n = 2754) and white (VA, n = 7987; non-VA, n = 4980) hypertensive men. RESULTS: In both groups, whites were older than African Americans (P<.05), had lower BP (P<.001), and had BP controlled to below 140/90 mm Hg more often on their last visit (P<.01). Blood pressure control to below 140/90 mm Hg was comparable among white hypertensive men at VA (55.6%) and non-VA (54.2%) settings (P = .12). In contrast, BP control was higher among African American hypertensive men at VA (49.4%) compared with non-VA (44.0%) settings (P<.01), even after controlling for age, numerous comorbid conditions, and rural-urban classification. African American hypertensive men received a comparable number of prescriptions for BP medications at VA sites (P = .18) and more prescriptions at non-VA sites than did whites (P<.001). African Americans had more visits in the previous year at VA sites (P<.001) and fewer visits at non-VA sites (P<.001) compared with whites. CONCLUSIONS: The ethnic disparity in BP control between African Americans and whites was approximately 40% less at VA than at non-VA health care sites (6.2% vs 10.2%; P<.01). Ensuring access to health care could constitute one constructive component of a national initiative to reduce ethnic disparities in BP control and cardiovascular risk.

Mechanisms of angiotensin II-induced expression of B2 kinin receptors.

Although the primary roles of the kallikreinkinin system and the renin-angiotensin system are quite divergent, they are often intertwined under pathophysiological conditions. We examined the effect of ANG II on regulation of B(2) kinin receptors (B2KR) in vascular cells. Vascular smooth muscle cells (VSMC) were treated with ANG II in a concentration (10(-9)-10(-6) M)- and time (0-24 h)-dependent manner, and B2KR protein and mRNA levels were measured by Western blots and PCR, respectively. A threefold increase in B2KR protein levels was observed as early as 6 h, with a peak response at 10(-7) M. ANG II (10(-7) M) also increased B2KR mRNA levels twofold 4 h after stimulation. Actinomycin D suppressed the increase in B2KR mRNA and protein levels induced by ANG II. To elucidate the receptor subtype involved in mediating this regulation, VSMC were pretreated with losartan (AT(1) receptor antagonist) and/or PD-123319 (AT(2) receptor antagonist) at 10 microM for 30 min, followed by ANG II (10(-7) M) stimulation. Losartan completely blocked the ANG II-induced B2KR increase, whereas PD-123319 had no effect. In addition, expression of B2KR mRNA levels was decreased in AT(1A) receptor knockout mice. Finally, to determine whether ANG II stimulates B2KR expression via activation of the MAPK pathway, VSMC were pretreated with an inhibitor of p42/p44(mapk) (PD-98059) and/or an inhibitor of p38(mapk) (SB-202190), followed by ANG II (10(-7) M) for 24 h. Selective inhibition of the p42/p44(mapk) pathway significantly blocked the ANG II-induced increase in B2KR expression. These findings demonstrate that ANG II regulates expression of B2KR in VSMC and provide a rationale for studying the interaction between ANG II and bradykinin in the pathogenesis of vascular dysfunction.