Greater Risk Of Incident Hypertension Research Articles

Abstract P474: Association Between Dietary Patterns and Incident Hypertension in Regards (REasons for Geographic And Regional Differences in Stroke) Participants

Background: The lifetime hypertension prevalence in the US is >70%. Dietary patterns may partially explain this overall risk. We sought to explore the association between dietary intake and risk of incident hypertension. Methods: REGARDS participants without hypertension at Visit 1 (2003-2007) were included, excluding those missing dietary data or Visit 2 follow-up (2013-2016). The exposure of interest was quartile of adherence to 5 dietary patterns previously determined among REGARDS participants using food frequency questionnaires and factor analysis: Convenience, Plant-Based, Sweets, Southern, and Alcohol/Salad (descriptions in Table 1). The outcome of interest was incident hypertension, defined as a blood pressure of ≥130/80 mmHg or the use of antihypertensive medication at follow up. Modified Poisson regression estimated risk ratios (RR), adjusting for demographics, socioeconomic factors, health behaviors, and medical conditions. Results: Of the 3,423 (mean [SD] age 61.6 [± 8.4] years, 58.5% women, 17.9% Black race), 42% (1,438) developed hypertension at median follow-up of 9 years. In unadjusted models, there was no clear association between Convenience, Plant-Based, or Sweets dietary patterns and incident hypertension (Table 1). High adherence to a Southern pattern was associated with incident hypertension. This association remained when adjusting for demographics, but not when adjusting for socioeconomic variables, health behaviors, and comorbid conditions. High adherence to the Alcohol/Salad dietary pattern also had no clear association with incident hypertension risk in the unadjusted model. However, in the fully adjusted model, there was greater risk of incident hypertension with greater adherence to the Alcohol/Salad pattern. Conclusions: Certain dietary patterns in REGARDS were associated with greater risk of incident hypertension. Future analyses to examine which food groups may be driving differential associations may help develop dietary strategies to reduce hypertension.

Cytokines, C-Reactive Protein, and Risk of Incident Hypertension in the REGARDS Study.

Hypertension is a highly prevalent cardiovascular disease risk factor that may be related to inflammation. Whether adverse levels of specific inflammatory cytokines relate to hypertension is unknown. The present study sought to determine whether higher levels of IL (interleukin)-1β, IL-6, TNF (tumor necrosis factor)-α, IFN (interferon)-γ, IL-17A, and CRP (C-reactive protein) are associated with a greater risk of incident hypertension. The REGARDS study (Reasons for Geographic and Racial Difference in Stroke) is a prospective cohort study that recruited 30 239 community-dwelling Black and White adults from the contiguous United States in 2003 to 2007 (visit 1), with follow-up 9 years later in 2013 to 2016 (visit 2). We included participants without prevalent hypertension who attended follow-up 9 years later and had available laboratory measures and covariates of interest. Poisson regression estimated the risk ratio of incident hypertension by level of inflammatory biomarkers. Among 1866 included participants (mean [SD] aged of 62 [8] years, 25% Black participants, 55% women), 36% developed hypertension. In fully adjusted models comparing the third to first tertile of each biomarker, there was a greater risk of incident hypertension for higher IL-1β among White (1.24 [95% CI, 1.01-1.53]) but not Black participants (1.01 [95% CI, 0.83-1.23]) and higher TNF-α (1.20 [95% CI, 1.02-1.41]) and IFN-γ (1.22 [95% CI, 1.04-1.42]) among all participants. There was no increased risk with IL-6, IL-17A, or CRP. Higher levels of IL-1β, TNF-α, and IFN-γ, representing distinct inflammatory pathways, are elevated in advance of hypertension development. Whether modifying these cytokines will reduce incident hypertension is unknown.

A longitudinal study of incident hypertension and its determinants in Indian adults aged 45 years and older: evidence from nationally representative WHO-SAGE study (2007-2015).

Hypertension (HT) is a leading cause of mortality and morbidity in developing countries. This study aimed to estimate the incidence of HT among adults aged 45 years and older in India and its associated risk factors. This study used longitudinal data from the Indian sample of the first and second waves of the World Health Organization Study on Global Ageing and Adult Health (WHO-SAGE). A bivariate analysis using Pearson's chi-square test was done to examine the associations of individual, lifestyle, and household characteristics with HT status reported in Wave 2. Incident HT changes were analyzed by adjusting for various covariates in the generalized estimating equation (logit link function) with an exchangeable correlation matrix and robust standard errors. The study found that during the 8-year period from 2007 to 2015, the incidence of HT in individuals aged 45 years and over was 20.8%. Pre-hypertensive individuals had an overall incidence rate of 31.1 per 1,000 [95% confidence interval (CI): 26.20-35.9] and a 2.24 times higher odds ratio: 2.24 (95% CI: 1.65-3.03) of developing incident HT compared to those who were normotensive. Adults aged 45 years and older, overweight/obese individuals, and women were more at risk of incident HT. One in five individuals had developed HT over 8 years, with a greater risk of incident HT among women than men. Pre-hypertensive individuals were at a greater risk of developing incident HT compared to normotensive individuals. The study recommends comprehensive and effective management of pre-HT to tackle the burden of HT.

Sex differences in Black Veterans with PTSD: women versus men have higher sympathetic activity, inflammation, and blunted cardiovagal baroreflex sensitivity.

Post-traumatic stress disorder (PTSD) is associated with greater risk of incident hypertension and cardiovascular disease (CVD). Inflammation and autonomic derangements are suggested as contributing mechanisms. Women and Black adults have higher CVD risk associated with stress; however, whether there is a sex difference in autonomic and inflammatory mechanisms among Black individuals with PTSD is not known. We hypothesized that Black women with PTSD have higher inflammation, sympathetic nervous system (SNS) activity and impaired baroreflex sensitivity (BRS). In 42 Black Veterans with PTSD (Women, N = 18 and Men, N = 24), we measured inflammatory biomarkers, continuous blood pressure (BP), heart rate (HR) and muscle sympathetic nerve activity (MSNA) at rest and during arterial BRS testing via the modified Oxford technique. Groups were matched for age and body mass index (BMI). Resting BP was similar between groups, but HR was higher (76 ± 12 vs. 68 ± 9 beats/min, p = 0.021) in women compared to men. Although women had lower PTSD symptoms severity (57 ± 17 vs. 68 ± 12 a.u.), resting MSNA (27 ± 13 vs. 16 ± 5 bursts/min, p = 0.003) was higher in women compared to men, respectively. Likewise, cardiovagal BRS was blunted (p = 0.002) in women (7.6 ± 4.3ms/mmHg) compared to men (15.5 ± 8.4ms/mmHg) while sympathetic BRS was not different between groups (p = 0.381). Black women also had higher (p = 0.020) plasma levels of interleukin-2 (IL-2). Black women with PTSD have higher resting HR and MSNA, greater impairment of cardiovagal BRS and possibly higher inflammation. These findings suggest a higher burden of autonomic and inflammatory derangements in Black women compared to Black men with PTSD.

Abstract P078: Excess Risk Of Hypertension Among Black Adults And The Mediating Effects Of Leptin: The Reasons For Geographic And Racial Differences In Stroke (REGARDS) Cohort Study

Background: Leptin is a hypertension-related adipokine. We previously found leptin to associate with greater risk of incident hypertension in non-obese adults. Relative to White adults, Black adults have higher circulating leptin concentration. As such, leptin may be a mediator of the excess burden of incident hypertension among Black adults. Methods: REGARDS recruited 30,239 Black or White adults aged ≥45 years from 48 US states. Leptin was measured from baseline samples among 4,400 participants who attended 2 visits 9 years apart. Modified Poisson regression estimated the relative risk (RR) of incident hypertension (≥140/90 mmHg or use of antihypertensives) of Black relative to White adults, adjusting for risk factors. Inverse odds ratio weighting estimated the % mediation by leptin of the excess hypertension RR among Black relative to White participants in 1,000 bootstrapped samples. Results: In 1,834 participants without prevalent hypertension (mean age 62, 56% women, 25% Black adults), incident hypertension developed in 47% of Black & 32% of White participants. The Table presents the RR for incident hypertension among Black relative to White adults. In the crude model, Black adults had a 52% greater risk of incident hypertension and leptin mediated 20% of this disparity. Similar associations were seen when adjusting for demographics, behaviors, and diseases. After adjusting for measures of adiposity, leptin no longer mediated the disparity. Conclusions: Leptin mediated approximately 20% of the Black-White disparity in hypertension incidence in crude and some adjusted models. These data support that this mediation acts through adiposity.

Abstract P092: Cell Adhesion Molecules And Incident Hypertension In Black And White Adults: The REasons For Geographic And Racial Differences In Stroke (REGARDS) Study

Background: High C-reactive protein (a nonspecific inflammatory biomarker) is a risk factor for incident hypertension. The role of specific inflammation pathways in hypertension’s origins are unresolved. E-selectin, ICAM-1, and VCAM are cell adhesion molecules expressed by endothelial cells that aid leukocyte adhesion during inflammation. Their association with incident hypertension is unclear. Objective: To determine risk of incident hypertension by level of E-selectin, ICAM-1, and VCAM. Methods: REGARDS enrolled 30,239 Black and White US adults aged ≥45 years from across the continental US in 2003-2006, with a second exam in 2013-2016. The Biomarkers as Mediators of Racial Disparities in Risk Factors (BioMedioR) study included 4,400 REGARDS participants who attended both exams. We excluded participants with hypertension or missing biomarkers of interest at baseline. Hypertension was defined using a 140/90 mm Hg threshold or self-reported use of blood pressure (BP) lowering medications. Modified Poisson regression estimated relative risk (RR) of incident hypertension by baseline E-Selectin, ICAM-1, and VCAM. Results: Among 1,923 normotensive participants (mean [SD] age 71 [8] years, 36% Black race, 51% women) with 9 years median follow up, 37% developed hypertension. Baseline E-selectin and ICAM-1 but not VCAM were higher among Black participants and obese participants. In multivariable adjusted models, higher E-selectin was associated with greater risk of incident hypertension among White but not Black adults (P interaction = 0.05) in all but the final model ( Table ). Higher ICAM-1 and VCAM were not associated with risk of hypertension in any model. Conclusion: In a prospective study of Black and White US adults, E-selectin was associated with incident hypertension among White adults except when adjusting for medical comorbidities, including baseline systolic BP. Modification of E-selectin through behavioral interventions or medical therapies might be tested to lower risk of hypertension development.

Abstract 056: Inflammatory Cytokines And Incident Hypertension In The REasons For Geographic And Racial Differences In Stroke (REGARDS) Study

Background: Higher C-reactive protein (CRP) is a risk factor for incident hypertension, but this non-specific inflammatory biomarker does not provide insight into specific immune pathways of hypertension. Here, we studied the role of selected cytokines in risk of incident hypertension to better elucidate these pathways. Objective: To determine the risk for incident hypertension disease among adults by level of IL-1β, IL-6, TNF-α, and IFN-γ. Methods: REGARDS recruited 30,239 Black and White adults aged ≥45 years from the 48 contiguous states in 2003-07. The Biomarkers as Mediators of Racial Disparities in Risk Factors (BioMedioR) substudy included 4,400 sex-race stratified REGARDS participants who also attendd a visit in 2013-16. We excluded those in BioMedioR with prevalent hypertension: 140/90 mm Hg threshold or self-reported antihypertensive medication use. Serum ELISAs assessed cytokines. Modified Poisson regression estimated relative risk (RR) of incident hypertension by detectable threshold (IL-1β; >0.06 pg/mL) or cytokine tertiles (tertile thresholds [33 rd & 66 th %iles] in pg/mL: IL-6, 0.56 & 0.94; TNF-α, 1.30 & 1.69; IFN-γ, 4.01 & 6.56). IL-1β was stratified on race because of a statistically significant interaction. Results: Among the 1,877 participants at risk for incident hypertension (mean [SD] age 62 [8] years, 36% Black race, 51% women), incident hypertension occurred in 31% of White adults and 45% of Black adults. With full adjustment ( Figure ), higher TNF-α and IFN-γ in everyone, and detectable IL-1β in White but not Black adults, were associated with greater incident hypertension risk. There was no association of higher IL-6 with incident hypertension. Conclusions: Among Black and White adults without prevalent hypertension, higher TNF-α, and IFN-γ, and detectable IL-1β (among White but not Black adults), were associated with greater risk of incident hypertension. Future basic and clinical research should study these inflammatory pathways toward developing hypertension prevention strategies.

Association of Resting Heart Rate With Blood Pressure and Incident Hypertension Over 30 Years in Black and White Adults: The CARDIA Study.

Few studies have assessed the association of resting heart rate (RHR) through young adulthood with incident hypertension by middle age. We investigated the association between RHR measured over 30 years with incident hypertension in a cohort of young Black and White men and women. A joint longitudinal time-to-event model consisting of a mixed random effects submodel, quadratic in follow-up time, and a survival submodel adjusted for confounders, was used to determine hazard ratios for a 10 bpm higher RHR. Race-sex specific effects were examined in a single joint model that included interactions of race-sex groups with longitudinal RHR. Out of 5115 participants enrolled in year 0 (1985-1986), after excluding prevalent cases of hypertension at baseline, 1615 men and 2273 women were included in the analytic cohort. Hypertension event rates per 1000 person-years were 42.5 and 25.7 in Black and White men, respectively, and 36.2 and 15.3 in Black and White women, respectively. The hazard ratios for a 10 bpm higher RHR were 1.47 (95% CI, 1.23-1.75), 1.51 (95% CI, 1.28-1.78), 1.48 (95% CI, 1.26-1.73), and 1.02, (95% CI, 0.89-1.17) for Black men, White men, White women, and Black women, respectively. Higher RHR during young adulthood is associated with a greater risk of incident hypertension by middle age. The association is similarly strong in Black men, White men, and White women, but absent in Black women, which may suggest racial differences in the effect of sympathetic nervous activity on hypertension among women.

Deportation Worry, Cardiovascular Disease Risk Factor Trajectories, and Incident Hypertension: A Community-Based Cohort Study.

BackgroundWorry about deportation has been associated with cardiovascular disease risk factors in cross‐sectional research. No research has evaluated this association longitudinally or examined the association between deportation worry and incident cardiovascular disease outcomes.Methods and ResultsWe used data from an ongoing community‐based cohort of 572 women primarily of Mexican origin. We estimated associations between self‐reported deportation worry and: (1) trajectories of blood pressure, body mass index, and waist circumference with linear mixed models, and (2) incident hypertension with Cox proportional hazards models. Nearly half (48%) of women reported “a lot,” 24% reported “moderate,” and 28% reported “not too much” deportation worry. Higher worry at baseline was associated with nonlinear systolic blood pressure and mean arterial pressure trajectories. For example, compared with not too much worry, a lot of worry was associated with a faster initial increase (β, interaction with linear year term: 4.10; 95% CI, 1.17–7.03) followed by a faster decrease in systolic blood pressure (β, interaction with quadratic year term: −0.80; 95% CI, −1.55 to −0.06). There was weak evidence of an association between deportation worry and diastolic blood pressure and no association with body mass index, waist circumference, or pulse pressure trajectories. Among 408 women without baseline hypertension, reporting a lot (hazard ratio, 2.17; 95% CI, 1.15–4.10) and moderate deportation worry (hazard ratio, 2.48; 95% CI, 1.17–4.30) were each associated with greater risk of incident hypertension compared with reporting not too much worry.ConclusionsDeportation worry may contribute to widening disparities in some cardiovascular disease risk factors and outcomes over time.

Symptom severity impacts sympathetic dysregulation and inflammation in post-traumatic stress disorder (PTSD)

Post-traumatic stress disorder (PTSD) is associated with a greater risk of incident hypertension and cardiovascular disease. Inflammation, impaired baroreflex sensitivity (BRS) decreased parasympathetic nervous system (PNS) and overactive sympathetic nervous system (SNS) activity are suggested as contributing mechanisms. Increasing severity of PTSD symptoms has been linked to greater cardiovascular risk; however, the impact of PTSD symptom severity on inflammation and autonomic control of blood pressure has not yet been explored. We hypothesized that increasing PTSD symptom severity is linked to higher inflammation, greater SNS activity, lower PNS reactivity and impaired BRS. Seventy Veterans participated in this study: 28 with severe PTSD ((Clinical Administered PTSD Scale (CAPS) > 60; S-PTSD), 16 with moderate PTSD (CAPS ≥ 45 ≤ 60; M-PTSD) and 26 Controls (CAPS < 45; NO-PTSD). We recorded continuous blood pressure (BP), heart rate (HR) via EKG, heart rate variability (HRV) markers reflecting PNS and muscle sympathetic nerve activity (MSNA) at rest, during arterial baroreflex sensitivity (BRS) testing via the modified Oxford technique, and during 3 min of mental stress via mental arithmetic. Blood samples were analyzed for 12 biomarkers of systemic and vascular inflammation. While BP was comparable between severity groups, HR tended to be higher (p = 0.055) in S-PTSD (76 ± 2 beats/min) than in Controls (67 ± 2 beats/min) but comparable to M-PTSD (70 ± 3 beats/min). There were no differences in resting HRV and MSNA between groups; however, cardiovagal BRS was blunted (p = 0.021) in S-PTSD (10 ± 1 ms/mmHg) compared to controls (16 ± 3 ms/mmHg) but comparable to M-PTSD (12 ± 2 ms/mmHg). Veterans in the S-PTSD group had a higher (p < 0.001) combined inflammatory score compared to both M-PTSD and NO-PTSD. Likewise, while mental stress induced similar SNS and cardiovascular responses between the groups, there was a greater reduction in HRV in S-PTSD compared to both M-PTSD and NO-PTSD. In summary, individuals with severe PTSD symptoms have higher inflammation, greater impairment of BRS, a trend towards higher resting HR and exaggerated PNS withdrawal at the onset of mental stress that may contribute to cardiovascular risk in severe PTSD.

C-reactive protein and incident hypertension in a worksite population of Japanese men.

Inflammation plays a key role in the pathogenesis of cardiovascular diseases via the development of atherosclerosis. Here, we evaluated the impact of serum C-reactive protein (CRP) and the white blood cell (WBC) count on the risk of hypertension in middle-aged Japanese men at a work site. We evaluated a total of 2991 Japanese male workers without hypertension who ranged in age from 18 to 64years (mean age 40.4±0.2years) at a worksite in 2010. The hazard ratio (HR) for incident hypertension was estimated according to quartile levels of serum high-sensitivity CRP (hs-CRP) or WBC count. These men were followed up for 5years from 2010 to 2015. During the follow-up period, 579 (19.4%) subjects developed hypertension. In a multivariable analysis, the risk of incident hypertension was significantly increased with higher hs-CRP levels: HR 1.00 (reference) for the lowest quartile, 1.39 (1.04-1.85) for the 2nd quartile, 1.46 (1.08-1.98) for the 3rd quartile, and 1.57 (1.17-2.11) for the highest quartile. In contrast, the WBC count was not associated with a greater risk of incident hypertension after multivariable adjustment. These findings suggest that higher levels of serum hs-CRP, but not the WBC count, are associated with the future incidence of hypertension in middle-aged Japanese men.

Initiation of Disease-Modifying Therapies in Rheumatoid Arthritis Is Associated With Changes in Blood Pressure.

This study reports the effect of disease-modifying therapies for rheumatoid arthritis (RA) on systolic and diastolic blood pressure (SBP, DBP) over 6 months and incident hypertension over 3 years in a large administrative database. We used administrative Veterans Affairs databases to define unique dispensing episodes of methotrexate, leflunomide, sulfasalazine, hydroxychloroquine, tumor necrosis factor inhibitors, and prednisone among patients with RA. Changes in SBP and DBP in the 6 months before disease-modifying antirheumatic drug initiation were compared with changes observed in the 6 months after initiation. The risk of incident hypertension within 3 years (new diagnosis code for hypertension and prescription for antihypertensive) was also assessed. Multivariable models and propensity analyses assessed the impact of confounding by indication. A total of 37,900 treatment courses in 21,216 unique patients contributed data. Overall, there were no changes in SBP or DBP in 6 months prior to disease-modifying antirheumatic drug initiation (all P > 0.62). In contrast, there was a decline in SBP (β = -1.08 [-1.32 to -0.85]; P < 0.0001) and DBP (β = -0.48 [-0.62 to -0.33]; P < 0.0001) over the 6 months following initiation. The greatest decline was observed among methotrexate and hydroxychloroquine users. Methotrexate users were 9% more likely to have optimal blood pressure (BP) after 6 months of treatment. Patients treated with leflunomide had increases in BP and a greater risk of incident hypertension compared with patients treated with methotrexate (hazard ratio, 1.53 [1.21-1.91]; P < 0.001). Blood pressure may improve with treatment of RA, particularly with methotrexate or hydroxychloroquine. Leflunomide use, in contrast, is associated with increases in BP and a greater risk of incident hypertension.

Vitamin D and hypertension: Prospective study and meta-analysis.

ObjectivesThe study sought to determine the link between vitamin D concentrations and incident hypertension in prospective study and meta-analysis.MethodsThe study was embedded in the Kailuan Study, a population-based cohort of adults that contains underground miners. In 2012, we studied 2,456 men and women free of prevalent hypertension, age 21 to 67 at baseline. Serum 25-hydroxyvitamin D was measured from previously frozen baseline samples using ELISA (Enzyme-Linked ImmunoadSorbent Assay). We use the logistic regression analysis to estimate the odd radio (ORs) 95% confidence intervals (CIs) for 25-hydroxyvitamin D [25(OH)D] concentrations with incident hypertension. To help place our new data in context, we conducted a systemic review and meta-analysis of previous prospective reports of vitamin D and hypertension.ResultsDuring a median follow-up of 2 years, 42.6% of the cohort (n = 1047) developed hypertension. Compared with the 25-hydroxyvitamin D >30ng/ml, 25-hydroxyvitamin D <20 ng/ml was associated with a greater hypertension risk (OR: 1.225 [95% CI: 1.010 to 1.485] p = 0.04), although the association was attenuated and not statistically significant after adjusting for potential confounders (OR: 1.092 [95% CI: 0.866 to 1.377] p = 0.456). This meta-analysis included seven prospective studies for 53,375 participants using adjusted HR founded a significant association between vitamin D deficiencies and incident hypertension (HRs = 1.235 (95% CI: 1.083 to 1.409, p = 0.002)).ConclusionLower serum 25-hydroxyvitamin D concentrations were not associated with a greater risk of incident hypertension. More research is needed to further determine the role of 25-hydroxyvitamin D in hypertension prevention and therapy.

Abstract 20: Fatty Liver is Associated with Greater Incidence of Cardiovascular Risk Factors

Introduction: Non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk for cardiovascular (CV) related-death. Prior studies have demonstrated a cross-sectional association between NAFLD and CV risk factors including hypertension, hyperlipidemia, and insulin resistance. Little is known about the relationship between NAFLD and incident CV risk factors in the American adult population. We hypothesized that, independent of overall adiposity, NAFLD is associated with incident CV risk factors. Methods: We conducted a longitudinal study of 1,645 Framingham Heart Study Third Generation Cohort participants (median age 44.0 years, 46.1% women) who attended examination 1 (2002-2005) and examination 2 (2008-2011) and participated in the multi-detector computed tomography (MDCT) sub-study (2002-2005). The median follow up duration was 6.2 years. We excluded participants with heavy alcohol use or with prevalent myocardial infarction and stroke at baseline. Liver fat was assessed using MDCT at the baseline examination. Odds ratios (OR) of incident CV risk factors per standard deviation increase of liver fat were estimated using logistic regression models with adjustment for multiple baseline covariates including BMI. Results: The prevalence of NAFLD was 16.6% in the present sample. In multivariable-adjusted models, liver fat was not associated with incident metabolic syndrome (OR 1.10, 95%CI: 0.88, 1.37), hypertriglyceridemia (OR 0.93, 95%CI: 0.75, 1.16), low high-density lipoprotein (OR 1.21, 95%CI: 0.88, 1.66), or prediabetes (OR 1.15, 95%CI: 0.95, 1.40). However, per standard deviation increase of liver fat, we observed a greater risk of incident hypertension (OR 1.22, 95%CI: 1.02-1.46, P-value=0.03) and incident type 2 diabetes (OR 1.45, 95%CI: 1.15-1.84, P-value=0.002). The association with liver fat and incident type 2 diabetes remained after additional adjustment for visceral adipose tissue volume (OR 1.42, 95%CI: 1.10-1.82, P-value=0.006). Conclusions: The present study demonstrates that higher level of liver fat is associated with increased incidence of hypertension and type 2 diabetes over 6 years. Future studies are needed to determine if interventions targeting individuals with NAFLD may reduce incident CV risk factors burden.

Association of 25-Hydroxyvitamin D and Parathyroid Hormone With Incident Hypertension: MESA (Multi-Ethnic Study of Atherosclerosis)

This study investigated whether lower 25-hydroxyvitamin D and higher parathyroid hormone concentrations are associated with incident hypertension. Disturbances in vitamin D metabolism are plausibly related to hypertension. MESA (Multi-Ethnic Study of Atherosclerosis) is a community-based, prospective cohort with baseline measurements obtained between 2000 and 2002. We studied 3,002 men and women free of prevalent cardiovascular disease and hypertension, age 45 to 84 years at baseline. Serum 25-hydroxyvitamin D and intact parathyroid hormone were measured from previously frozen baseline samples using liquid chromatography-mass spectroscopy and a 2-site immunoassay, respectively. We used a complementary log-log model with interval censoring to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for 25-hydroxyvitamin D and parathyroid hormone concentrations with incident hypertension through 2010. During a median follow-up of 9.0 years, 41% of the cohort (n = 1,229) developed hypertension. Mean serum 25-hydroxyvitamin D was 26.3 ± 11.2 ng/ml and mean parathyroid hormone was 41.2 ± 17.3 pg/ml. Compared with 25-hydroxyvitamin D ≥30 ng/ml, 25-hydroxyvitamin D <20 ng/ml was associated with a greater hypertension risk (HR: 1.28 [95% CI: 1.09 to 1.50]), although the association was attenuated and not statistically significant after adjusting for potential confounders (HR: 1.13 [95% CI: 0.96 to 1.33]). Compared with parathyroid hormone <33 pg/ml, parathyroid hormone ≥65 pg/ml was associated with a significantly greater risk of hypertension (HR: 1.27 [95% CI: 1.01 to 1.59]) after adjusting for potential confounders. Lower 25-hydroxyvitamin D concentrations were not associated with a greater risk of incident hypertension. Higher serum parathyroid hormone concentrations showed a significant, but statistically marginal, relationship to the development of hypertension. These findings will require further confirmation. (Multi-Ethnic Study of Atherosclerosis; NCT00005487).

Pre-Hypertension: Rationale for Pharmacotherapy

Pre-hypertension, defined as blood pressure 120-139/80-89mmHg, affects ~70 million people in the US. Blood pressures in the upper half of the pre-hypertensive range are linked with roughly threefold greater risk of incident hypertension than normal blood pressure <120/<80mmHg, with an incidence rate of 8-20% annually. Blood pressures in the upper half of the pre-hypertensive range also roughly double risk for cardiovascular events, even in the absence of progression to hypertension. Despite excess risk, guidelines recommend lifestyle interventions only for people with pre-hypertension in the absence of diabetes mellitus or clinical cardiovascular or chronic kidney disease. While efficacious, lifestyle changes have limited population effectiveness as Americans are heavier and their nutritional patterns less DASH-like than before DASH was published. Prevalent hypertension is higher in African Americans than Caucasians, but prevalent pre-hypertension is similar. African Americans experience a more rapid transition from pre-hypertension to hypertension than Caucasians with pre-hypertension. Interventions that normalize racial differences in incident hypertension could, over time, improve racial equity in prevalent hypertension and related clinical complications. Individuals with pre-hypertension can be safely treated with antihypertensive medications to significantly reduce incident hypertension. Given the evidence, practical clinical trials in African Americans with pre-hypertension to reduce and eliminate racial disparities in incident hypertension have merit. The results of these trials could provide the foundation for clinical guidelines to reduce racial disparities in prevalent hypertension and associated clinical cardiovascular and renal diseases.

The relationship between inflammation, obesity and risk for hypertension in the Multi-Ethnic Study of Atherosclerosis (MESA)

It has been suggested that inflammation is important in the aetiology of hypertension and that this may be most relevant among obese persons. To study this, we examined the independent relationships between obesity, inflammation-related proteins (interleukin-6 (IL-6), C-reactive protein (CRP) and fibrinogen) and risk for hypertension in the Multi-Ethnic Study of Atherosclerosis (MESA). Hypertension status, defined as a blood pressure ≥140/90 mm Hg or a history of hypertension and use of blood pressure medications, was determined at baseline and two subsequent exams over 5 years. Among 3543 non-hypertensives at baseline, 714 individuals developed incident hypertension by Exam 3. Cox proportional hazard models were used to determine the relationship between baseline levels of IL-6, CRP and fibrinogen and future risk of hypertension. One s.d. difference in baseline concentration of IL-6, CRP or fibrinogen was associated with 20-40% greater risk of incident hypertension. This risk was attenuated after accounting for other hypertension risk factors (hazard ratio (HR) IL-6: 1.13 (95% CI: 1.04-1.23); CRP: 1.11 (95% CI: 1.02-1.21); fibrinogen 1.0 (95% CI: 0.92-1.08)). Conversely, obesity was an independent risk factor for hypertension risk, minimally impacted by other covariates, including IL-6 and CRP (HR 1.72 (95% CI: 1.36-2.16)). IL-6 and CRP did not modify the relationship between obesity and hypertension, though an adjusted twofold greater risk was observed for obese individuals with a CRP >3 mg l⁻¹ compared with CRP <1 mg l⁻¹. The relationship between inflammation-related proteins and hypertension risk was predominantly explained by other hypertension risk factors. Obesity, independent of inflammation, remained a potent risk factor for future hypertension.

Abstract 5414: Serum Uric Acid Levels versus the Abdominal Obesity in Relation to Incident Hypertension in a Prospective Study in a Chinese Community

BACKGROUND: Most Caucasian-based epidemiological data have shown that hyperuricemia is associated with the risk of hypertension, but whether this association is independent of adiposity and other vascular risk factors remains unclear. Therefore, we evaluated the associations of serum uric acid versus abdominal obesity with incident hypertension in a large Chinese Han population. METHODS: We conducted a community-based prospective cohort study comprising 7220 participants (mean age 37 years; 74% men) in the Qingdao Health and Nutrition Examination Survey in China, who were free from hypertension at study entry in 1999–2000. During 4-year follow-up, 1370 men (19.0%) and 208 women (11.0%) had developed hypertension. RESULTS: After adjustment for age, body mass index, waist circumference, and other covariates, the relative risks (RR) of developing hypertension according to uric acid quartiles were 0.97, 1.23, and 1.39 [95% confidence interval (CI), 1.16–1.68; P trend=0.008] for men and 1.49, 1.58, 1.85 (95%CI, 1.06–3.24; P trend=0.007) for women. The associations of hypertension with serum uric acid increased with the component number of metabolic syndrome (none, one, two, or more), which is defined by the criteria of the modified Adult Treatment Panel III and an Asian-specific waist circumference cut-off point (≥90 cm in men, ≥80 in women). Given that abdominal obesity is an important underlying risk factor for metabolic syndrome, in joint analyses of waist circumference and serum uric acid, participants with abdominal obesity had a consistently higher risk than those without. Compared with those in the lowest uric acid quartile and without abdominal obesity, participants who were in the highest quartile and also had abdominal obesity had a 3.0-fold and 3.4-fold greater risk of incident hypertension in men (95%CI, 1.56–2.97) and in women (95%CI, 2.10–3.81), respectively. To minimize the bias from reverse causality due to subclinical hypertension, analyses after excluding the first 2 years of follow-up showed similar results. CONCLUSIONS: These data suggest a positive association between serum uric acid and incident hypertension during short-term follow-up in a Chinese population. The association was partly mediated through abdominal obesity. 1

Plasma Uric Acid and Hypertension in a Chinese Community: Prospective Study and Metaanalysis

Hyperuricemia has been positively associated with hypertension, but whether this association is independent of adiposity and other cardiovascular risk factors remains a matter of debate. We conducted a community-based prospective cohort study comprising 7220 participants (mean age 37 years; 73.8% men) in the Qingdao Port Health and Nutrition Examination Survey in China, who were free from hypertension at study entry in 1999-2000. During 4-year follow-up, 1370 men (19.0%) and 208 women (11.0%) had developed hypertension. After adjustment for age, body mass index, and other covariates, the relative risks (RRs) of developing hypertension comparing the highest and lowest uric acid quartiles were 1.55 (95% CI 1.10-2.19; P for trend <0.001) for men and 1.91 (1.12-3.25; P for trend <0.001) for women. After additional adjustment for abdominal obesity, the RRs comparing the participants in the highest and lowest quartiles of uric acid were 1.39 (1.16-1.68; P for trend 0.003) for men and 1.85 (1.06-3.24; P for trend 0.006) for women. In joint analysis, compared with those in the lowest uric acid quartile and without abdominal obesity, participants who were in the highest quartile and also had abdominal obesity had a 3.0- and 3.4-fold greater risk of incident hypertension (1.56-3.97 for men and 2.10-3.81 for women, respectively). These data suggest a positive association between plasma uric acid and incidence of hypertension during short-term follow-up in a Chinese population. The association between hyperuricemia and hypertension was partly mediated by abdominal obesity.

C-reactive protein concentration and incident hypertension in young adults: the CARDIA study.

There is increasing evidence that C-reactive protein (CRP) concentration, a measure of inflammation, is an independent risk factor for the development of hypertension in older adults. However, it is unknown whether a similar relationship exists in younger individuals. The Coronary Artery Risk Development in Young Adults (CARDIA) study was initiated in 1985-1986 to determine the factors that are associated with coronary risk development in young adults. C-reactive protein concentrations were measured in 3919 African American and white men and women enrolled in CARDIA using blood specimens from the year 7 examination (1992-1993), when the age of the cohort was 25 to 37 years, and the year 15 examination (2000-2001). In unadjusted analyses, CRP concentrations greater than 3 mg/L, compared with those less than 1 mg/L, was associated with a 79% greater risk of incident hypertension (odds ratio [OR], 1.79; 95% confidence interval [CI], 1.40-2.28). However, CRP concentration did not predict risk of incident hypertension after adjusting for year 7 body mass index (BMI) (OR, 1.14; 95% CI, 0.86-1.53) or year 7 BMI and other potential confounders (OR, 1.13; 95% CI, 0.83-1.52). In addition, year 7 CRP concentration was not associated with change in systolic or diastolic blood pressure after adjusting for BMI (P = .10 and P = .70, respectively). These findings were similar within each of the race- and sex-specific groups. C-reactive protein is associated with hypertension in young adults, but in contrast to the finding in older populations, the association is no longer present after adjusting for BMI.