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BackgroundOnly a handful of genetic discovery efforts in apparent treatment-resistant hypertension (aTRH) have been described.MethodsWe conducted a case-control genome-wide association study of aTRH among persons treated for hypertension, using data from 10 cohorts of European ancestry (EA) and 5 cohorts of African ancestry (AA). Cases were treated with 3 different antihypertensive medication classes and had blood pressure (BP) above goal (systolic BP ≥ 140 mm Hg and/or diastolic BP ≥ 90 mm Hg) or 4 or more medication classes regardless of BP control (nEA = 931, nAA = 228). Both a normotensive control group and a treatment-responsive control group were considered in separate analyses. Normotensive controls were untreated (nEA = 14,210, nAA = 2,480) and had systolic BP/diastolic BP < 140/90 mm Hg. Treatment-responsive controls (nEA = 5,266, nAA = 1,817) had BP at goal (

BACKGROUND The association with cardiovascular disease (CVD) is stronger for mean systolic blood pressure (SBP) estimated using ambulatory blood pressure monitoring (ABPM) vs. office measurements. Determining whether this is due to ABPM providing more measurement reliability or greater ecological validity can inform its use. METHODS We estimated the association of mean SBP based on 2 office measurements and 2, 5, 10, and 20 measurements on ABPM with incident CVD in the Jackson Heart Study (n  = 773). Hazard ratios (HRs) for CVD were estimated per standard deviation higher mean SBP. CVD events were defined by incident fatal or non-fatal stroke, non-fatal myocardial infarction, or fatal coronary heart disease. RESULTS There were 80 CVD events over a median of 15 years. The adjusted HRs for incident CVD were 1.03 (95% CI: 0.90–1.19) for mean office SBP and 1.30 (95% CI: 1.12–1.50), 1.34 (95% CI: 1.15–1.56), 1.36 (95% CI: 1.17–1.59), and 1.38 (95% CI: 1.17–1.63) for mean SBP using the first 2, 5, 10, and 20 ABPM readings. The difference in the HRs for incident CVD ranged from 0.26 (95% CI: 0.07–0.46) to 0.35 (95% CI: 0.15–0.54) when comparing mean office SBP vs. 2, 5, 10, or 20 sequential ABPM readings. The association with incident CVD was also stronger for mean SBP based on 2, 5, 10, and 20 randomly selected ABPM readings vs. 2 office readings. CONCLUSIONS Mean SBP based on 2 ABPM readings vs. 2 office measurements had a stronger association with CVD events. The increase in the strength of the association with more ABPM readings was small. [ABSTRACT FROM AUTHOR]

Introduction Stroke and ischemic heart disease are the most common causes of death in adults worldwide (1). Whereas myocardial infarction is primarily caused by coronary artery atherosclerosis, ischemic stroke (IS) [...], Protease-activated receptor 4 (PAR4) (gene F2RL3) harbors a functional dimorphism, rs773902 A/G (encoding Thr120/Ala120, respectively) and is associated with greater platelet aggregation. The A allele frequency is more common in Black individuals, and Black individuals have a higher incidence of ischemic stroke than White individuals. However, it is not known whether the A allele is responsible for worse stroke outcomes. To directly test the in vivo effect of this variant on stroke, we generated mice in which F2rl3 was replaced by F2RL3, thereby expressing human PAR4 (hPAR4) with either Thr120 or Ala120. Compared with hPAR4 Ala120 mice, hPAR4 Thr120 mice had worse stroke outcomes, mediated in part by enhanced platelet activation and platelet-neutrophil interactions. Analyses of 7,620 Black subjects with 487 incident ischemic strokes demonstrated the AA genotype was a risk for incident ischemic stroke and worse functional outcomes. In humanized mice, ticagrelor with or without aspirin improved stroke outcomes in hPAR4 Ala120 mice, but not in hPAR4 Thr120 mice. P selectin blockade improved stroke outcomes and reduced platelet-neutrophil interactions in hPAR4 Thr120 mice. Our results may explain some of the racial disparity in stroke and support the need for studies of nonstandard antiplatelet therapies for patients expressing PAR4 Thr120.

This article discusses the issue of low adherence to antihypertensive medication and its impact on blood pressure control and cardiovascular outcomes. It highlights the potential benefits of therapeutic drug monitoring, a diagnostic test that objectively assesses medication adherence, in improving adherence and lowering blood pressure. The article presents the results of a randomized trial that tested whether sharing therapeutic drug monitoring results with patients improves medication adherence and blood pressure control. However, the trial did not find a significant difference in adherence or blood pressure between the intervention and usual care groups. The article emphasizes the challenges of conducting trials to improve blood pressure control and suggests the need for additional research to address the issues of uncontrolled blood pressure and low medication adherence. [Extracted from the article]

Hypertension is a leading risk factor for cardiovascular disease mortality. African Americans (AAs) have the highest prevalence of hypertension in the United States, and to alleviate the burden of hypertension in this population, better control of blood pressure (BP) is needed. Previous studies have shown considerable interpersonal differences in BP response to antihypertensive treatment, suggesting a genetic component. Utilizing data from 4297 AA participants randomized to chlorthalidone from the Genetics of Hypertension Associated Treatments (GenHAT) study, we aimed to identify variants associated with the efficacy of chlorthalidone. An additional aim was to find variants that contributed to changes in fasting glucose (FG) in these individuals. We performed genome-wide association analyses on the change of systolic and diastolic BP (SBP and DBP) over six months and FG levels over 24 months of treatment. We sought replication in the International Consortia of Pharmacogenomics Studies. We identified eight variants statistically associated with BP response and nine variants associated with FG response. One suggestive LINC02211-CDH9 intergenic variant was marginally replicated with the same direction of effect. Given the impact of hypertension in AAs, this study implies that understanding the genetic background for BP control and glucose changes during chlorthalidone treatment may help prevent adverse cardiovascular events in this population. [ABSTRACT FROM AUTHOR]

Background: African Americans (AAs) suffer a higher stroke burden due to hypertension. Identifying genetic contributors to stroke among AAs with hypertension is critical to understanding the genetic basis of the disease, as well as detecting at-risk individuals. Methods: In a population comprising over 10,700 AAs treated for hypertension from the Genetics of Hypertension Associated Treatments (GenHAT) and Reasons for Geographic and Racial Differences in Stroke (REGARDS) studies, we performed an inverse variance-weighted meta-analysis of incident stroke. Additionally, we tested the predictive accuracy of a polygenic risk score (PRS) derived from a European ancestral population in both GenHAT and REGARDS AAs aiming to evaluate cross-ethnic performance. Results: We identified 10 statistically significant (p < 5.00E-08) and 90 additional suggestive (p < 1.00E-06) variants associated with incident stroke in the meta-analysis. Six of the top 10 variants were located in an intergenic region on chromosome 18 (LINC01443-LOC644669). Additional variants of interest were located in or near the COL12A1, SNTG1 , PCDH7 , TMTC1 , and NTM genes. Replication was conducted in the Warfarin Pharmacogenomics Cohort (WPC), and while none of the variants were directly validated, seven intronic variants of NTM proximal to our target variants, had a p -value <5.00E-04 in the WPC. The inclusion of the PRS did not improve the prediction accuracy compared to a reference model adjusting for age, sex, and genetic ancestry in either study and had lower predictive accuracy compared to models accounting for established stroke risk factors. These results demonstrate the necessity for PRS derivation in AAs, particularly for diseases that affect AAs disproportionately. Conclusion: This study highlights biologically plausible genetic determinants for incident stroke in hypertensive AAs. Ultimately, a better understanding of genetic risk factors for stroke in AAs may give new insight into stroke burden and potential clinical tools for those among the highest at risk. [ABSTRACT FROM AUTHOR]

Background The American Heart Association created the Life's Simple 7 (LS7) metrics to promote cardiovascular health (CVH) by achieving optimal levels of blood pressure, cholesterol, blood sugar, physical activity, diet, weight, and smoking status. The degree to which psychosocial factors such as stress and depression impact one's ability to achieve optimal CVH is unclear, particularly among hypertensive African Americans. Methods Cross-sectional analyses included 1,819 African Americans with hypertension participating in the Jackson Heart Study (2000–2004). Outcomes were LS7 composite and individual component scores (defined as poor, intermediate, ideal). High perceived chronic stress was defined as the top quartile of Weekly Stress Inventory scores. High depressive symptoms were defined as Center for Epidemiologic Studies Depression scale scores of ≥16. We compared 4 groups: high stress alone; high depressive symptoms alone; high stress and high depressive symptoms; low stress and low depressive symptoms (reference) using linear regression for total LS7 scores and logistic regression for LS7 components. Results Participants with both high stress and depressive symptoms had lower composite LS7 scores (B [95% confidence interval] = −0.34 [−0.65 to −0.02]) than those with low stress and depressive symptoms in unadjusted and age/sex-adjusted models. They also had poorer health status for smoking (odds ratio [95% confidence interval] = 0.52 [0.35–0.78]) and physical activity (odds ratio [95% confidence interval] = 0.71 [0.52–0.95]) after full covariate adjustment. Conclusions The combination of high stress and high depressive symptoms was associated with poorer LS7 metrics in hypertensive African Americans. Psychosocial interventions may increase the likelihood of engaging in behaviors that promote optimal CVH. [ABSTRACT FROM AUTHOR]

Objectives. To determine factors that explain the higher Black:White cardiovascular disease (CVD) mortality rates among US adults. Methods. We analyzed data from the Reasons for Geographic and Racial Differences in Stroke study from 2003 to 2017 to estimate Black:White hazard ratios (HRs) for CVD mortality within subgroups younger than 65 years and aged 65 years or older. Results. Among 29 054 participants, 41.0% who were Black and 54.9% who were women, 1549 CVD deaths occurred. Among participants younger than 65 years, the demographic-adjusted Black:White CVD mortality HR was 2.23 (95% confidence interval [CI] = 1.87, 2.65) and 1.21 (95% CI = 1.00, 1.47) after full adjustment. Among participants aged 65 years or older, the demographic-adjusted Black:White CVD mortality HR was 1.58 (95% CI = 1.39, 1.79) and 1.12 (95% CI = 0.97, 1.29) after full adjustment. When we used mediation analysis, socioeconomic status explained 21.2% (95% CI = 13.6%, 31.4%) and 38.0% (95% CI = 20.9%, 61.7%) of the Black:White CVD mortality risk difference among participants younger than 65 years and aged 65 years or older, respectively. CVD risk factors explained 56.6% (95% CI = 42.0%, 77.2%) and 41.3% (95% CI = 22.9%, 65.3%) of the Black:White CVD mortality difference for participants younger than 65 years and aged 65 years or older, respectively. Conclusions. The higher Black:White CVD mortality risk is primarily explained by racial differences in socioeconomic status and CVD risk factors. [ABSTRACT FROM AUTHOR]

OBJECTIVE Recent studies have suggested that prediabetes is associated with an increased risk for cardiovascular disease (CVD) only among individuals with concomitant hypertension. RESEARCH DESIGN AND METHODS We analyzed the association between prediabetes and CVD by hypertension status among 3,313 black adults in the Jackson Heart Study (JHS) without diabetes or a history of CVD at baseline (2000–2004). Prediabetes was defined as fasting plasma glucose between 100 and 125 mg/dL or hemoglobin A1c between 5.7 and 6.4% (39 and 46 mmol/mol). Hypertension was defined as systolic/diastolic blood pressure ≥140/90 mmHg and/or self-reported antihypertensive medication use. Participants were followed for incident CVD events and all-cause mortality through 31 December 2014. RESULTS Overall, 35% of JHS participants did not have prediabetes or hypertension, 18% had prediabetes alone, 22% had hypertension alone, and 25% had both prediabetes and hypertension. Compared with participants without either condition, the multivariable-adjusted hazard ratios for CVD events among participants with prediabetes alone, hypertension alone, and both prediabetes and hypertension were 0.86 (95% CI 0.51, 1.45), 2.09 (1.39, 3.14), and 1.93 (1.28, 2.90), respectively. Among participants with and without hypertension, there was no association between prediabetes and an increased risk for CVD (0.78 [0.46, 1.34] and 0.94 [0.70, 1.26], respectively). No association was present between prediabetes and all-cause mortality among participants with or without hypertension. CONCLUSIONS Regardless of hypertension status, prediabetes was not associated with an increased risk for CVD or all-cause mortality in this cohort of black adults. [ABSTRACT FROM AUTHOR]

BACKGROUND Higher dietary phosphorus is associated with left ventricular hypertrophy and mortality, which are blood pressure (BP)-related outcomes. For this reason, we hypothesized that dietary phosphorus may be associated with adverse clinic and ambulatory BP patterns. METHODS Our study included 973 African American adults enrolled in the Jackson Heart Study (2000–2004) with 24-hour ambulatory BP monitoring (ABPM) data at baseline. We quantified dietary phosphorus from a validated Food Frequency Questionnaire as follows: (i) absolute daily intake, (ii) ratio of phosphorus-to-protein intake, (iii) phosphorus density, and (iv) energy-adjusted phosphorus intake. Using multivariable linear regression, we determined associations between dietary phosphorus intake and systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure in clinic and over daytime, nighttime, and 24-hour periods from ABPM. Extent of nocturnal BP dipping was also assessed. Using logistic regression, we modeled relationships between dietary phosphorus intake and clinically relevant qualitative BP phenotypes, such as masked, sustained, or white-coat hypertension and normotension. RESULTS There were no statistically significant associations between phosphorus intake and SBP or pulse pressure in adjusted models. Most metrics of higher phosphorus intake were associated with lower daytime, nighttime, and clinic DBP. Higher phosphorus intake was not associated with clinic or ABPM-defined hypertension overall, but most metrics of higher phosphorus intake were associated with lower odds of sustained hypertension compared to sustained normotension, white-coat hypertension, and masked hypertension. There were no associations between dietary phosphorus and nocturnal BP dipping. CONCLUSIONS These data do not support a role for higher phosphorus intake and higher BP in African Americans. [ABSTRACT FROM AUTHOR]

It is unclear whether black patients with chronic kidney disease (CKD) vs those without CKD who take antihypertensive medication have an increased risk for apparent treatment-resistant hypertension (aTRH). The authors analyzed 1741 Jackson Heart Study participants without aTRH taking antihypertensive medication at baseline. aTRH was defined as uncontrolled blood pressure while taking three antihypertensive medication classes or taking four or more antihypertensive medication classes, regardless of blood pressure level. CKD was defined as an albumin to creatinine ratio ≥30 mg/g or estimated glomerular filtration rate <60 mL/min/1.73 m2 . Over 8 years, 20.1% of participants without CKD and 30.5% with CKD developed aTRH. The multivariable-adjusted hazard ratio for aTRH comparing participants with CKD vs those without CKD was 1.45 (95% CI, 1.12-1.86). Participants with an albumin to creatinine ratio ≥30 vs <30 mg/g (hazard ratio, 1.44; 95% CI, 1.04-2.00) and estimated glomerular filtration rate of 45 to 59 mL/min/1.73 m2 and <45 vs ≥60mL/min/1.73 m2 (hazard ratio, 1.60 [95% CI, 1.16-2.20] and 2.05 [95% CI, 1.28-3.26], respectively) were more likely to develop aTRH. [ABSTRACT FROM AUTHOR]

Several modifiable health behaviors and health factors that comprise the Life's Simple 7-a cardiovascular health metric-have been associated with hypertension risk. We determined the association between cardiovascular health and incident hypertension in JHS (the Jackson Heart Study)-a cohort of blacks. We analyzed participants without hypertension or cardiovascular disease at baseline (2000-2004) who attended ≥1 follow-up visit in 2005 to 2008 or 2009 to 2012 (n=1878). Body mass index, physical activity, diet, cigarette smoking, blood pressure (BP), total cholesterol, and fasting glucose were assessed at baseline and categorized as ideal, intermediate, or poor using the American Heart Association's Life's Simple 7 definitions. Incident hypertension was defined at the first visit wherein a participant had systolic BP ≥140 mm Hg, diastolic BP ≥90 mm Hg, or self-reported taking antihypertensive medication. The percentage of participants with ≤1, 2, 3, 4, 5, and 6 ideal Life's Simple 7 components was 6.5%, 22.4%, 34.4%, 25.2%, 10.0%, and 1.4%, respectively. No participants had 7 ideal components. During follow-up (median, 8.0 years), 944 (50.3%) participants developed hypertension, including 81.3% with ≤1 and 11.1% with 6 ideal components. The multivariable-adjusted hazard ratios (95% confidence interval) for incident hypertension comparing participants with 2, 3, 4, 5, and 6 versus ≤1 ideal component were 0.80 (0.61-1.03), 0.58 (0.45-0.74), 0.30 (0.23-0.40), 0.26 (0.18-0.37), and 0.10 (0.03-0.31), respectively (Ptrend <0.001). This association was present among participants with baseline systolic BP <120 mm Hg and diastolic BP <80 mm Hg and separately systolic BP 120 to 139 mm Hg or diastolic BP 80 to 89 mm Hg. Blacks with better cardiovascular health have lower hypertension risk. [ABSTRACT FROM AUTHOR]

Background: In SPRINT (Systolic Blood Pressure Intervention Trial), a systolic blood pressure (SBP) goal of <120 mm Hg resulted in lower cardiovascular disease (CVD) risk compared with an SBP goal of <140 mm Hg.Objectives: The purpose of this study was to estimate the prevalence, number, and characteristics of U.S. adults meeting SPRINT eligibility criteria and determine the broader population to whom SPRINT could be generalized.Methods: We conducted a cross-sectional, population-based study using data from the National Health and Nutrition Examination Survey, 2007 to 2012. The SPRINT inclusion criteria were age ≥50 years, SBP 130 to 180 mm Hg depending on the number of antihypertensive medication classes being taken, and high CVD risk (history of coronary heart disease, estimated glomerular filtration rate of 20 to 59 ml/min/1.73 m(2), 10-year CVD risk ≥15%, or age ≥75 years). Exclusion criteria were diabetes, history of stroke, >1 g in 24 h of proteinuria daily, heart failure, estimated glomerular filtration rate <20 ml/min/1.73 m(2), or receiving dialysis. Treated hypertension was defined by self-reported use of medication to lower blood pressure with ≥1 class of antihypertensive medication identified through a pill bottle review.Results: Overall, 7.6% (95% confidence interval [CI]: 7.0% to 8.3%) or 16.8 million (95% CI: 15.7 to 17.8 million) U.S. adults, and 16.7% (95% CI: 15.2% to 18.3%) or 8.2 million (95% CI: 7.6 to 8.8 million) adults with treated hypertension met the SPRINT eligibility criteria. Among both the overall U.S. population and adults with treated hypertension, the percentage meeting SPRINT eligibility criteria increased with older age, was higher among males than females, and was higher among non-Hispanic whites compared with non-Hispanic blacks or Hispanics. Of U.S. adults eligible for SPRINT, 51.0% (95% CI: 47.8% to 54.1%) or 8.6 million (95% CI: 8.0 to 9.1 million) were not treated for hypertension.Conclusions: A substantial percentage of U.S. adults meet the eligibility criteria for SPRINT. [ABSTRACT FROM AUTHOR]

Many adults with elevated clinic blood pressure (BP) have lower BP when measured outside the clinic. This phenomenon, the "white-coat effect," may be larger among older adults, a population more susceptible to the adverse effects of low BP. The authors analyzed data from 257 participants in the Jackson Heart Study with elevated clinic BP (systolic/diastolic BP [SBP/DBP] ≥140/90 mm Hg) who underwent ambulatory BP monitoring (ABPM). The white-coat effect for SBP was larger for participants 60 years and older vs those younger than 60 years in the overall population (12.2 mm Hg, 95% confidence interval [CI], 9.2-15.1 mm Hg and 8.4 mm Hg, 95% CI, 5.7-11.1, respectively; P=.06) and among those without diabetes or chronic kidney disease (15.2 mm Hg, 95% CI, 10.1-20.2 and 8.6 mm Hg, 95% CI, 5.0-12.3, respectively; P=.04). After multivariable adjustment, clinic SBP ≥150 mm Hg vs <150 mm Hg was associated with a larger white-coat effect. Studies are needed to investigate the role of ABPM in guiding the initiation and titration of antihypertensive treatment, especially among older adults. [ABSTRACT FROM AUTHOR]

Introduction: Current guidelines suggest using cystatin-C to confirm a reduced creatinine-based estimated glomerular filtration rate (eGFRcr) when the latter is thought to be inaccurate. Older adults have reduced muscle mass, which may affect the accuracy of eGFRcr. We evaluated the use of cystatin-C-based eGFR (eGFRcys) to confirm reduced eGFRcr among adults ≥ 80 years of age and, for comparison, younger adults.Material and Methods: We analyzed data from 3,059 REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants with reduced eGFRcr (< 60 ml/min/1.73 m(2)) enrolled in 2003-2007 who were not on dialysis. eGFRcr and eGFRcys were calculated using age, sex and race-adjusted equations. Confirmed reduced eGFRcr was defined as eGFRcys < 60 ml/min/1.73 m(2). Prevalence of chronic kidney disease complications at baseline and all-cause mortality up to March 2012 were calculated. Analyses were stratified by age: < 65, 65-79 and ≥ 80 years.Results: Among participants < 65, 65-79 and ≥ 80 years of age, 76.5%, 85.7% and 92.5%, respectively, had reduced eGFRcr confirmed with eGFRcys (p < 0.001). Among participants ≥ 80 years of age, those with reduced eGFRcr confirmed with eGFRcys had higher prevalence of hypertension (79.1% vs. 65.1%, p = 0.03) and albuminuria (38.3% vs. 22.7%, p = 0.04) and higher risk for all-cause mortality (hazard ratio: 2.43; 95% confidence interval: 1.19-5.01) as compared with those in whom reduced eGFRcr was not confirmed by eGFRcys.Conclusions: Reduced eGFRcr was confirmed using eGFRcys for the vast majority of adults ≥ 80 years. These results suggest that using cystatin-C to confirm a reduced eGFRcr may not be necessary among the oldest old. [ABSTRACT FROM AUTHOR]

Background: Studies suggest 24-h blood pressure (BP) variability has prognostic value for cardiovascular disease. Several factors associated with high 24-h BP variability are also common among individuals with chronic kidney disease (CKD). We hypothesized 24-h BP variability would be higher for individuals with versus without CKD. Methods: We analyzed 1,022 Jackson Heart Study participants who underwent ambulatory blood pressure monitoring (ABPM). Twenty-four hour BP variability was defined by two metrics: day-night standard deviation (SDdn) and average real variability (ARV). CKD was defined as ACR ≥30 mg/g or eGFR <60 mL/min/1.73 m². Results: The mean SDdn of systolic BP (SBP) was 10.2 ± 0.2 and 9.1 ± 0.1 mmHg and the mean ARV of SBP was 9.2 ± 0.2 and 8.6 ± 0.1 mmHg for those with and without CKD, respectively (each p ≤ 0.001). After adjustment for age and sex, SDdn and ARV were 0.98 mmHg (95 % CI 0.59, 1.38) and 0.52 mmHg (95 % CI 0.18, 0.86), respectively, higher among participants with versus without CKD. These differences were not statistically significant after further multivariable adjustment including 24-h mean SBP. Older age, and higher total cholesterol and 24-h mean SBP were associated with higher SDdn and ARV of SBP among participants with CKD. Mean SDdn and ARV of diastolic BP (DBP) were higher for participants with versus without CKD but these associations were not present after multivariable adjustment. Conclusion: Data from the current study suggest that CKD is associated with higher 24-h BP variability, but the association is primarily explained by higher mean BP among those with CKD. [ABSTRACT FROM AUTHOR]

Background: Variants in CUBN, the gene encoding cubilin, a proximal tubular transport protein, have been associated with albuminuria and vitamin B12 (B12) deficiency. We hypothesized that low levels of B12 would be associated with albuminuria in a population-based cohort. Methods: We analyzed participants from the Framingham Heart Study (n = 2965, mean age 58 years, 53% female) who provided samples for plasma B12. Logistic regression models adjusted for covariates including homocysteine were constructed to test the association between B12 and prevalent albuminuria (UACR ≥17 mg/g [men] and ≥25 mg/g [women]) and reduced kidney function (defined as an eGFR < 60 ml/min/1.73 m², RKF). Because of a significant interaction between B12 and homocysteine in the prevalent RKF model (p = 0.005), the model was stratified by the median homocysteine levels. Logistic regression models were constructed to test the association between B12 and incident albuminuria and RKF. The results were replicated in 4445 participants from NHANES 2003-2004. Results: Baseline B12 levels ranged from 50-1690 pg/ml. Elevated B12 was associated with prevalent albuminuria (OR 1.44 per 1 SD increase, 95% CI 1.10-1.87) and RKF (OR 1.83, 95% CI 1.30-2.60). However after stratifying by median homocysteine levels, this relationship remained only in the higher homocysteine stratum. There was no association between B12 and incident albuminuria (OR 1.17, 95% CI 0.79 - 1.73) or RKF (OR 1.45, 95% CI 0.97 - 1.88). In the NHANES cohort, elevated B12 was associated with RKF after full covariate adjustment (OR 3.06, 95% CI 2.30-4.08). There was no association with albuminuria. Conclusion: In participants with high baseline homocysteine levels, increased plasma B12 was associated with RKF. [ABSTRACT FROM AUTHOR]

Visit-to-visit variability of blood pressure (BP) has been associated with cardiovascular disease (CVD) and mortality in some but not all studies. We conducted a systematic review and meta-analysis to examine the association between visit-to-visit variability of BP and CVD and all-cause mortality. Medical databases were searched through June 4, 2014, for studies meeting the following eligibility criteria: adult participants; BP measurements at ≥3 visits; follow-up for CVD, coronary heart disease, stroke, or mortality outcomes; events confirmed via database, death certificate, or event ascertainment committee; and adjustment for confounders. Data were extracted by 2 reviewers and pooled using a random-effects model. Overall, 8870 abstracts were identified of which 37 studies, representing 41 separate cohorts, met inclusion criteria. Across studies, visit-to-visit variability of systolic BP and diastolic BP showed significant associations with outcomes in 181 of 312 (58.0%) and 61 of 188 (32.4%) analyses, respectively. Few studies provided sufficient data for pooling risk estimates. For each 5 mm Hg higher SD of systolic BP, the pooled hazard ratio for stroke across 7 cohorts was 1.17 (95% confidence interval [CI], 1.07-1.28), for coronary heart disease across 4 cohorts was 1.27 (95% CI, 1.07-1.51), for CVD across 5 cohorts was 1.12 (95% CI, 0.98-1.28), for CVD mortality across 5 cohorts was 1.22 (95% CI, 1.09-1.35), and for all-cause mortality across 4 cohorts was 1.20 (95% CI, 1.05-1.36). In summary, modest associations between visit-to-visit variability of BP and CVD and all-cause mortality are present in published studies. However, these findings are limited by the small amount of data available for meta-analysis. [ABSTRACT FROM AUTHOR]

The authors examined trends in systolic blood pressure ( SBP) and diastolic blood pressure ( DBP) and the prevalence, awareness, treatment, and control of hypertension in 1988-1994 (n=1164), 1999-2004 (n=1,026), and 2005-2010 (n=1048) among US adults 80 years and older in serial National Health and Nutrition Examination Surveys. Hypertension was defined as SBP ≥140 mm Hg, DBP ≥90 mm Hg, or use of antihypertensive medication. Awareness and treatment were defined by self-report and control as SBP/ DBP<140/90 mm Hg. Mean SBP decreased from 147.3 mm Hg to 140.1 mm Hg and mean DBP from 70.2 mm Hg to 59.4 mm Hg between 1988-1994 and 2005-2010. The prevalence, awareness, and treatment of hypertension each increased over time. Controlled hypertension increased from 30.4% in 1988-1994 to 53.1% in 2005-2010. The proportion of patients taking 3 classes of antihypertensive medication increased from 7.0% to 30.9% between 1988-1994 and 2005-2010. Increases in awareness, treatment, and control of hypertension and antihypertensive polypharmacy have been observed among very old US adults. [ABSTRACT FROM AUTHOR]

Objectives: MMP-9 and -12 function in tissue remodeling and may play roles in cardiovascular disease (CVD). We assessed associations of four MMP polymorphisms and three antihypertensive drugs with cardiovascular outcomes. Methods: Hypertensives (n = 42,418) from a double-blind, randomized, clinical trial were randomized to chlorthalidone, amlodipine, lisinopril, or doxazosin treatment (mean follow up, 4.9 years). The primary outcome was coronary heart disease (CHD). Secondary outcomes included combined CHD, all CVD outcomes combined, stroke, heart failure (HF), and mortality. Genotype-treatment interactions were tested. Results: There were 38,698 participants genotyped for at least one of the polymorphisms included here. For MMP9 R668Q (rs2274756), lower hazard ratios (HRs) were found for AA subjects for most outcomes when treated with chlorthalidone versus amlodipine (eg., CCHD: GG = 1.00, GA = 1.01, AA = 0.64; P = 0.038). For MMP9 R279Q (rs17576), modest pharmacogenetic findings were observed for combined CHD and the composite CVD outcome. For MMP12 N122S (rs652438), lower HRs were observed for CHD in subjects carrying at least one G allele and being treated with chlorthalidone versus lisinopril (CHD: AA = 1.07, AG = 0.80, GG = 0.49; P = 0.005). In the lisinopril-amlodipine comparison, higher HRs were observed for participants having at least one G allele at the MMP12 N122S locus (CHD: AA = 0.94, AG = 1.19, GG = 1.93; P = 0.041). For MMP12 282A.G (rs2276109), no pharmacogenetic effect was found for the primary outcome, although lower HRs were observed for AA homozygotes in the chlorthalidone-amlodipine comparison for HF (P = 0.015). Conclusions: We observed interactions between antihypertensive drugs and MMP9 and MMP12 for CHD and composite CVD. The data suggest that these genes may provide useful clinical information with respect to treatment decisions. [ABSTRACT FROM AUTHOR]

B See related article, pp 1800-1807 b Preeclampsia is a pregnancy-specific syndrome characterized by hypertension and proteinuria, or other target organ damage, occurring after 20 weeks of gestation. They found that pulse wave velocity was weakly correlated with systolic BPV and was elevated throughout pregnancy in women with preeclampsia, while there was no correlation between BRS and systolic BPV and little difference in BRS across pregnancy in women who developed preeclampsia compared with those who did not. Further studies are needed to investigate whether BPV predicts preeclampsia in nonwhite women, given the marked racial differences in hypertension etiology, and to examine potential biological mechanisms contributing to increased BPV in preeclampsia. [Extracted from the article]

Postprandial lipemia (PPL) is an important risk factor for cardiovascular disease. Inter-individual variation in the dietary response to a meal is known to be influenced by genetic factors, yet genes that dictate variation in postprandial lipids are not completely characterized. Genetic studies of the plasma lipidome can help to better understand postprandial metabolism by isolating lipid molecular species which are more closely related to the genome. We measured the plasma lipidome at fasting and 6 h after a standardized high-fat meal in 668 participants from the Genetics of Lipid-Lowering Drugs and Diet Network study (GOLDN) using ultra-performance liquid chromatography coupled to (quadrupole) time-of-flight mass spectrometry. A total of 413 unique lipids were identified. Heritable and responsive lipid species were examined for association with single-nucleotide polymorphisms (SNPs) genotyped on the Affymetrix 6.0 array. The most statistically significant SNP findings were replicated in the Amish Heredity and Phenotype Intervention (HAPI) Heart Study. We further followed up findings from GOLDN with a regional analysis of cytosine-phosphate-guanine (CpGs) sites measured on the Illumina HumanMethylation450 array. A total of 132 lipids were both responsive to the meal challenge and heritable in the GOLDN study. After correction for multiple testing of 132 lipids (α = 5 × 10−8/132 = 4 × 10−10), no SNP was statistically significantly associated with any lipid response. Four SNPs in the region of a known lipid locus (fatty acid desaturase 1 and 2/FADS1 and FADS2) on chromosome 11 had p < 8.0 × 10−7 for arachidonic acid FA(20:4). Those SNPs replicated in HAPI Heart with p < 3.3 × 10−3. CpGs around the FADS1/2 region were associated with arachidonic acid and the relationship of one SNP was partially mediated by a CpG (p = 0.005). Both SNPs and CpGs from the fatty acid desaturase region on chromosome 11 contribute jointly and independently to the diet response to a high-fat meal. [ABSTRACT FROM AUTHOR]