Rikki M. Tanner

Visit-to-Visit Variability of Blood Pressure and Cardiovascular Disease and All-Cause Mortality A Systematic Review and Meta-Analysis

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.

Generalizability of SPRINT Results to the U.S. Adult Population

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.

Prevalence of Apparent Treatment-Resistant Hypertension among Individuals with CKD

BACKGROUND AND OBJECTIVES Apparent treatment-resistant hypertension is defined as systolic/diastolic BP ≥ 140/90 mmHg with concurrent use of three or more antihypertensive medication classes or use of four or more antihypertensive medication classes regardless of BP level. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The prevalence of apparent treatment-resistant hypertension among Reasons for Geographic and Racial Differences in Stroke study participants treated for hypertension (n=10,700) was determined by level of estimated GFR and albumin-to-creatinine ratio, and correlates of apparent treatment-resistant hypertension among those participants with CKD were evaluated. CKD was defined as an albumin-to-creatinine ratio ≥ 30 mg/g or estimated GFR<60 ml/min per 1.73 m(2). RESULTS The prevalence of apparent treatment-resistant hypertension was 15.8%, 24.9%, and 33.4% for those participants with estimated GFR ≥ 60, 45-59, and <45 ml/min per 1.73 m(2), respectively, and 12.1%, 20.8%, 27.7%, and 48.3% for albumin-to-creatinine ratio<10, 10-29, 30-299, and ≥ 300 mg/g, respectively. The multivariable-adjusted prevalence ratios (95% confidence intervals) for apparent treatment-resistant hypertension were 1.25 (1.11 to 1.41) and 1.20 (1.04 to 1.37) for estimated GFR levels of 45-59 and <45 ml/min per 1.73 m(2), respectively, versus ≥ 60 ml/min per 1.73 m(2) and 1.54 (1.39 to 1.71), 1.76 (1.57 to 1.97), and 2.44 (2.12 to 2.81) for albumin-to-creatinine ratio levels of 10-29, 30-299, and ≥ 300 mg/g, respectively, versus albumin-to-creatinine ratio<10 mg/g. After multivariable adjustment, men, black race, larger waist circumference, diabetes, history of myocardial infarction or stroke, statin use, and lower estimated GFR and higher albumin-to-creatinine ratio levels were associated with apparent treatment-resistant hypertension among individuals with CKD. CONCLUSIONS This study highlights the high prevalence of apparent treatment-resistant hypertension among individuals with CKD.

Age-Specific Association of Reduced Estimated Glomerular Filtration Rate and Albuminuria with All-Cause Mortality

BACKGROUND AND OBJECTIVES It has been suggested that reduced estimated GFR (eGFR) among older adults does not necessarily reflect a pathologic phenomenon. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We examined the association between eGFR and albumin-to-creatinine ratio (ACR) and all-cause mortality stratified by age (45 to 59.9, 60 to 69.9, 70 to 79.9, and ≥80 years) among 24,350 U.S. adults in the population-based REasons for Geographic and Racial Differences in Stroke (REGARDS) study. A spot urine sample was used to calculate ACR, and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was used to calculate eGFR. All-cause mortality was assessed over a median follow-up of 4.5 years. RESULTS Among participants ≥80 years of age (n = 1669), the age, race, gender, and geographic region of residence adjusted hazard ratios (95% confidence intervals) for mortality associated with eGFR levels of 45 to 59.9 and <45 ml/min per 1.73 m(2), versus ≥60 ml/min per 1.73 m(2), were 1.6 (1.3 - 2.1) and 2.2 (1.7 - 2.9), respectively. Also, among participants ≥80 years of age, the hazard ratios for mortality associated with ACR levels of 10 to 29.9, 30 to 299.9, and ≥300 mg/g, versus <10 mg/g, were 1.7 (1.3 - 2.1), 2.5 (1.9 - 3.3), and 5.1 (3.6 - 7.4), respectively. These associations were present after further multivariable adjustment and within the younger age groupings studied. CONCLUSIONS These data suggest that reduced eGFR and albuminuria confer an increased risk for mortality in all age groups, including adults ≥80 years of age.

Association of the Metabolic Syndrome With Atrial Fibrillation Among United States Adults (from the REasons for Geographic and Racial Differences in Stroke [REGARDS] Study)

Metabolic syndrome (MS) and atrial fibrillation (AF) are associated with increased cardiovascular disease morbidity and mortality. This analysis evaluated the association between MS and AF in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. MS was defined using criteria recommended in the joint interim statement from several international societies. AF was defined by electrocardiogram (ECG) and/or self-report and by ECG alone. In patients with 0, 1, 2, 3, 4, and 5 MS components, prevalences of AF by ECG and/or self-report were 5.5%, 7.7%, 8.2%, 9.2%, 9.6%, and 11.5%, respectively (p for trend <0.001). After multivariable adjustment, each MS component except serum triglycerides was significantly associated with AF. The multivariable-adjusted odds ratio for AF, defined by ECG and/or or self-reported history, comparing those with to those without MS was 1.20 (95% confidence interval 1.10 to 1.29). Results were consistent when AF was defined by ECG alone (odds ratio 1.15, 95% confidence interval 0.92 to 1.39). In conclusion, MS is associated with an increased prevalence of AF. Further studies investigating a potential mechanism for this excess risk are warranted.

Trends in hypertension prevalence, awareness, treatment, and control among US adults 80 years and older, 1988-2010.

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.

Obesity, metabolic health, and the risk of end-stage renal disease.

Obesity is associated with chronic kidney disease progression. Whether metabolic risk factors modify this association is unclear. Here we examined associations of body mass index (BMI) and metabolic health with risk of end-stage renal disease (ESRD) in the Reason for Geographic and Racial Differences in Stroke (REGARDS) study. Among 21,840 participants eligible for analysis, 247 developed ESRD (mean follow-up of 6.3 years). Metabolic health significantly modified the association of BMI with ESRD. In models stratified by presence or absence of metabolic syndrome and adjusted for demographic, lifestyle and clinical factors, higher BMI was associated with lower risk of ESRD in those without (hazard ratio per 5 kg/m2 increase in BMI 0.70, 95%CI 0.52,0.95), but not those with (hazard ratio, 1.06) metabolic syndrome. In models stratified by weight and metabolic health, compared to normal weight (BMI 18.5–24.9 kg/m2) participants without metabolic syndrome the overweight individuals (BMI 25–29.9) and obese individuals (BMI of 30 or more) with metabolic syndrome had greater risk of ESRD (hazard ratios of 2.03 and 2.29, respectively), whereas obesity without the metabolic syndrome was associated with lower risk of ESRD (hazard ratio 0.47). Thus, higher BMI is associated with lower ESRD risk in those without but not those with metabolic syndrome.

Waist Circumference, Body Mass Index, and ESRD in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) Study

BACKGROUND The association between waist circumference and end-stage renal disease (ESRD) remains poorly explored. STUDY DESIGN Longitudinal population-based cohort. SETTING & PARTICIPANTS Participants in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) Study (n=30,239) with information for body mass index (BMI), waist circumference, spot urine albumin-creatinine ratio (ACR), and estimated glomerular filtration rate (eGFR; n=26,960). PREDICTOR Elevated waist circumference or BMI. OUTCOMES & MEASUREMENTS Incident cases of ESRD were identified through linkage of REGARDS participants with the US Renal Data System. RESULTS Mean baseline age was 64.8 years, 45.8% were men, and 40.3% were black. Overall, 297 (1.1%) individuals developed ESRD during a median of 6.3 years. After adjustment for all covariates including waist circumference, no significant association was noted between BMI categories and ESRD incidence compared to BMI of 18.5 to 24.9 kg/m2 (referent). Higher waist circumference categories showed significantly increased hazard rates of ESRD, with waist circumference ≥ 108 cm in women and ≥122 cm in men (highest category) showing a 3.97-fold higher hazard rate (95% CI, 2.10-6.86) for ESRD compared to waist circumference < 80 cm in women and <94 cm in men (referent) after adjusting for demographic factors and BMI. However, no significant association was noted between any waist circumference category and ESRD incidence after adjustment for obesity-associated comorbid conditions and baseline ACR and eGFR. LIMITATIONS Short follow-up period (6.3 years) to assess ESRD risk among adults with eGFRs>60 mL/min/1.73 m2. CONCLUSIONS In this cohort of older adults, obesity as measured by waist circumference is associated with higher ESRD risk even with adjustment for BMI, whereas obesity as measured by BMI is not associated with higher ESRD risk after adjustment for waist circumference. However, no significant association is noted between increased waist circumference and ESRD risk after adjustment for obesity-related comorbid conditions, eGFR, and ACR.

Racial and Gender Differences in Stroke Severity, Outcomes and Treatment in Patients with Acute Ischemic Stroke

BACKGROUND Previous research has indicated that women and blacks have worse outcomes after acute ischemic stroke (AIS). Little research has been done to investigate the combined influence of race and gender in the presentation, treatment, and outcome of patients with AIS. We sought to determine the association of race and gender on initial stroke severity, thrombolysis, and functional outcome after AIS. METHODS AIS patients who presented to 2 academic medical centers in the United States (2004-2011) were identified through prospective registries. In-hospital strokes were excluded. Stroke severity, measured by admission National Institutes of Health Stroke Scale (NIHSS) scores, treatment with tissue plasminogen activator (tPA), neurologic deterioration (defined by a ≥2-point increase in NIHSS score), and functional outcome at discharge, measured by the modified Rankin Scale, were investigated. These outcomes were compared across race/gender groups. A subanalysis was conducted to assess race/gender differences in exclusion criteria for tPA. RESULTS Of the 4925 patients included in this study, 2346 (47.6%) were women and 2310 (46.9%) were black. White women had the highest median NIHSS score on admission (8), whereas white men had the lowest median NIHSS score on admission (6). There were no differences in outcomes between black men and white men. A smaller percentage of black women than white women were treated with tPA (27.6% versus 36.6%, P < .0001), partially because of a greater proportion of white women presenting within 3 hours (51% versus 45.5%, P = .0005). Black women had decreased odds of poor functional outcome relative to white women (odds ratio [OR] = .85, 95% confidence interval [CI] .72-1.00), but after adjustment for baseline differences in age, NIHSS, and tPA use, this association was no longer significant (OR = 1.2, 95% CI .92-1.46, P = .22). Black women with an NIHSS score less than 7 on admission were at lower odds of receiving tPA than the other race/gender groups, even after adjusting for arriving within 3 hours and admission glucose (OR = .66, 95% CI .44-.99, P = .0433). CONCLUSION Race and gender were not significantly associated with short-term outcome, although black women were significantly less likely to be treated with tPA. Black women had more tPA exclusions than any other group. The primary reason for tPA exclusion in this study was not arriving within 3 hours of stroke symptom onset. Given the growth in incident strokes projected in minority groups in the next 4 decades, identifying factors that contribute to black women not arriving to the emergency department in time are of great importance.

Contrasting Cholesterol Management Guidelines for Adults with CKD

The Kidney Disease Improving Global Outcomes Lipid Work Group recommends statins for adults ≥50 years old with CKD. The American College of Cardiology/American Heart Association endorses statins for adults with atherosclerotic cardiovascular disease, adults with LDL cholesterol≥190 mg/dl, and adults 40-79 years old with LDL cholesterol=70-189 mg/dl and diabetes or a 10-year predicted risk for atherosclerotic cardiovascular disease ≥7.5% estimated using the Pooled Cohort risk equations. Using data from the Reasons for Geographic and Racial Differences in Stroke Study, we calculated the agreement for statin treatment between these two guidelines for adults 50-79 years old with CKD (eGFR<60 ml/min per 1.73 m(2) or albuminuria≥30 mg/g) not on dialysis. We assessed the validity of the Pooled Cohort risk equations in individuals with CKD. Study participants were enrolled between 2003 and 2007, and we report incident cardiovascular disease events (stroke and coronary heart disease) through December of 2010. Among 4726 participants with CKD, 2366 (50%) were taking statins, and 1984 (42%) were recommended statins by the American College of Cardiology/American Heart Association guideline but not taking them. Overall, 376 (8%) participants did not meet the American College of Cardiology/American Heart Association criteria for initiating statin treatment. Cardiovascular disease incidence was low (3.0/1000 person-years; 95% confidence interval, 0.1 to 5.9) among these participants. The Pooled Cohort risk equations were well calibrated (Hosmer-Lemeshow chi-squared=2.7, P=0.45) with moderately good discrimination (C index, 0.71; 95% confidence interval, 0.65 to 0.77). In conclusion, these guidelines show high concordance for statin treatment for adults with CKD.