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author:("entner, Paul")
1.  Relation between Leukocyte Telomere Length and Incident Coronary Heart Disease Events (From the 1995 Canadian Nova Scotia Health Survey) 
The American journal of cardiology  2013;111(7):962-967.
Leukocyte telomere length has been proposed as a biomarker of cellular aging and atherosclerosis. We sought to determine whether leukocyte telomere length is independently associated with incident coronary heart disease (CHD) in the general population. Telomere length was measured using a polymerase chain reaction method for participants enrolled in the 1995 Nova Scotia Health Survey (n=1,917). The primary endpoint was first occurrence of fatal and non-fatal CHD events. During a mean follow-up of 8.7 years, 164 fatal or non-fatal CHD events occurred. Compared to participants in the longest tertile of telomere length, those in the middle and shortest tertiles had increased incidence of CHD events (6.2, 11.2 and 12.2 per 1000 person-years, respectively). After adjustment for demographics, traditional risk factors and inflammatory markers including hs-CRP, IL-6, and sICAM-1, those in the middle tertile had significantly elevated risk for incident CHD (hazard ratio [HR] 1.63, 95% CI 1.07–2.51, p=0.02) compared to the longest tertile, whereas the risk for those in the shortest tertile was non-significantly elevated (HR 1.25, 95% CI 0.82–1.90, p=0.30). In conclusion, these findings do not support a linear association between leukocyte telomere length and incident CHD risk in the general population.
PMCID: PMC3602395  PMID: 23375186
coronary heart disease; telomere; risk prediction
2.  Sex Differences in Barriers to Antihypertensive Medication Adherence: Findings From the Cohort Study of Medication Adherence Among Older Adults (CoSMO) 
We assessed whether socio-demographic, clinical, health care system, psychosocial, and behavioral factors are differentially associated with low antihypertensive medication adherence scores among older men and women.
Design / Setting
A cross-sectional analysis using baseline data from the Cohort Study of Medication Adherence in Older Adults (CoSMO, n=2,194).
Low antihypertensive medication adherence was defined as a score <6 on the 8-item Morisky Medication Adherence Scale. Risk factors for low adherence were collected using telephone surveys and administrative databases.
The prevalence of low medication adherence scores did not differ according to sex (15.0% in women and 13.1% in men p=0.208). In sex-specific multivariable models, having issues with medication cost and practicing fewer lifestyle modifications for blood pressure control were associated with low adherence scores among both men and women. Factors associated with low adherence scores in men but not women included reduced sexual functioning (OR = 2.03; 95% CI: 1.31, 3.16 for men and OR = 1.28; 95% CI: 0.90, 1.82 for women), and BMI ≥25 (OR = 3.23; 95% CI: 1.59, 6.59 for men and 1.23; 95% CI: 0.82, 1.85 for women). Factors associated with low adherence scores in women but not men included dissatisfaction with communication with their healthcare provider (OR = 1.75; 95% CI: 1.16, 2.65 for women and OR =1.16 95% CI: 0.57, 2.34 for men) and depressive symptoms (OR = 2.29; 95% CI: 1.55, 3.38 for women and OR = 0.93; 95% CI: 0.48, 1.80 for men).
Factors associated with low antihypertensive medication adherence scores differed according to sex. Interventions designed to improve adherence in older adults should be tailored to account for the sex of the target population.
PMCID: PMC3628283  PMID: 23528003
medication adherence; hypertension; older adults; gender differences
3.  Association of posttraumatic stress disorder and depression with all-cause and cardiovascular disease mortality and hospitalization among Hurricane Katrina survivors with end-stage renal disease 
American journal of public health  2013;103(4):e130-e137.
To determine the association of psychiatric symptoms in the year after Hurricane Katrina with subsequent hospitalization and mortality in end-stage renal disease (ESRD) patients.
A prospective cohort of ESRD patients (n=391) treated at 9 hemodialysis centers in the New Orleans area in the weeks before Hurricane Katrina were assessed for PTSD and depression symptoms via telephone interview 9–15 months later. Two combined outcomes through August 2009 (maximum 3.5 years follow-up) were analyzed: (1) all-cause and (2) cardiovascular-related hospitalization and mortality.
Twenty-four percent of participants screened positive for PTSD, and 46% for depression; 158 participants died (79 cardiovascular deaths) and 280 participants were hospitalized (167 for cardiovascular related causes). Positive depression screen was associated with 33% higher risk for all-cause (HR = 1.33, 95% CI, 1.06–1.66), and cardiovascular-related hospitalization and mortality (HR = 1.33, 95% CI: 1.01 – 1.76). PTSD was not significantly associated with either outcome.
Depression in the year after Hurricane Katrina was associated with increased risk of hospitalization and mortality in ESRD patients, underscoring the long-term consequences of natural disasters for vulnerable populations.
PMCID: PMC3673270  PMID: 23409901
4.  C-reactive protein level and the incidence of eligibility for statin therapy: the Multi-Ethnic Study of Atherosclerosis (MESA) 
Clinical cardiology  2012;36(1):15-20.
Given the results of the JUPITER trial, statin initiation may be considered for individuals with elevated high sensitivity C-reactive protein (CRP). However, if followed prospectively, many individuals with elevated CRP may become statin-eligible, limiting the impact of elevated CRP as a treatment indication. This analysis estimates the proportion of people with elevated CRP that become statin eligible over time.
We followed 2,153 Multi-Ethnic Study of Atherosclerosis (MESA) participants free of cardiovascular disease (CVD) and diabetes with LDL-cholesterol (LDL-C) <130 mg/dL at baseline to determine the proportion who become eligible for statins over 4.5 years. The proportion eligible for statin therapy, defined by the National Cholesterol Education Program (NCEP) 2004 updated guidelines, was calculated at baseline and during follow-up stratified by baseline CRP level (≥2 mg/L).
At baseline, 47% of the 2,153 participants had elevated CRP. Among participants with elevated CRP, 29% met NCEP criteria for statins, compared to 28% without elevated CRP at baseline. By 1.5 years later, 26% and 22% (p=0.09) of those with and without elevated CRP at baseline reached NCEP LDL-C criteria and/or had started statins, respectively. These increased to 42% and 39% (p=0.24) at 3 years and 59% and 52% (p=0.01) at 4.5 years following baseline.
A substantial proportion of those with elevated CRP did not achieve NCEP based statin eligibility over 4.5 years of follow-up. These findings suggest that many patients with elevated CRP may not receive the benefits of statins if CRP is not incorporated into the NCEP screening strategy.
PMCID: PMC3953418  PMID: 22886783
5.  Generic Medications and Blood Pressure Control in Diabetic Hypertensive Subjects 
Diabetes Care  2013;36(3):591-597.
To investigate temporal improvements in blood pressure (BP) control in subjects with diabetes and policy changes regarding generic antihypertensives.
In a cross-sectional study we used logistic regression models to investigate the temporal relationship between access to generic antihypertensive medications and BP control (<130/80 mmHg) in 5,375 subjects (mean age, 66 ± 9 years; 61% African American) with diabetes and hypertension (HTN) enrolled in the national Results from the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort study between 2003 and 2007. At enrollment, BP was measured and medications in the home determined by medication label review by a trained professional. Generic antihypertensive medication status was ascertained from the U.S. Food and Drug Administration.
The percentage of subjects accessing generically available antihypertensive medications increased significantly from 66% in 2003 to 81% in 2007 (P < 0.0001), and the odds of achieving a BP <130/80 mmHg in 2007 was 66% higher (odds ratio 1.66 [95% CI 1.30–2.10]) than in 2003. Nevertheless, <50% of participants achieved this goal. African American race, male sex, limited income, and medication nonadherence were significant predictors of inadequate BP control. There was no significant relationship between access to generic antihypertensives and BP control when other demographic factors were included in the model (0.98 [0.96–1.00]).
Among African American and white subjects with HTN and diabetes, BP control remained inadequate relative to published guidelines, and racial disparities persisted. Although access to generic antihypertensives increased, this was not independently associated with improved BP control, suggesting that poor BP control is multifactorial.
PMCID: PMC3579377  PMID: 23150284
6.  Geographic Variation in CKD Prevalence and ESRD Incidence in the United States: Results From the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study 
It is not known whether geographic differences in the prevalence of chronic kidney disease (CKD) exist and are associated with end-stage renal disease (ESRD) incidence rates across the US.
Study Design
Cross-sectional and ecologic.
Setting & Participants
White (n=16,410) and black (n=11,109) participants from across the continental US in the population-based Reasons for Geographic and Racial Differences in Stroke (REGARDS) study.
Geographic region, defined by the 18 Networks of the US ESRD Network Program.
Outcomes & Measurements
Albuminuria, defined as an albumin-creatinine ratio ≥30 mg/g and reduced estimated glomerular filtration rate (eGFR), defined as levels <60 ml/min/1.73m2, were measured in the REGARDS study. ESRD incidence rates were obtained from the US Renal Data System.
For whites, the Network-specific prevalence of albuminuria ranged from 8.4% (95% CI, 3.3%–13.5%) in Network 15 to 14.8% (95% CI, 8.0%–21.6%) in Network 3, and reduced eGFR ranged from 4.3% (95% CI, 2.0%–6.6%) in Network 4 to 16.7% (95% CI, 12.7%–20.7%) in Network 7. For blacks, the prevalence of albuminuria ranged from 12.1% (95% CI, 8.7%–15.5%) in Network 5 to 26.5% (95% CI, 16.7%–36.3%) in Network 4, and reduced eGFR ranged from 6.7% (95% CI, 5.0%–8.4%) in Network 17/18 to 13.4% (95% CI, 7.8%–19.1%) in Network 12. The Spearman correlation coefficients for the prevalence of albuminuria and reduced eGFR with Network-specific ESRD incidence rates were 0.49 and 0.24, respectively, for whites and 0.29 and 0.25, respectively, for blacks.
There were few cases of albuminuria and reduced eGFR in some geographic regions.
In the US, substantial geographic variations in the prevalence of albuminuria and reduced eGFR exist but were only modestly correlated with ESRD incidence, suggesting the CKD burden may not explain the geographic variation in ESRD incidence.
PMCID: PMC3659181  PMID: 23228944
7.  Behavioral Mechanisms, Elevated Depressive Symptoms, and the Risk for Myocardial Infarction or Death in Individuals with Coronary Heart Disease (A Reason for Geographic and Racial Differences in Stroke [REGARDS] Study) 
To determine whether behavioral mechanisms explain the association between depressive symptoms and myocardial infarction (MI) or death in individuals with coronary heart disease (CHD).
Depressive symptoms are associated with increased morbidity and mortality in individuals with CHD, but it is unclear how much behavioral mechanisms contribute to this association.
The study included 4,676 participants with a history of CHD. Elevated depressive symptoms were defined as scores ≥4 on the Center for Epidemiologic Studies Depression 4-item Scale. The primary outcome was definite/probable MI or death from any cause. Incremental proportional hazards models were constructed by adding demographics, comorbidities and medications, then four behavioral mechanisms (alcohol use, smoking, physical inactivity, and medication non-adherence).
At baseline, 638 (13.6%) participants had elevated depressive symptoms. Over a median 3.8 years of follow up, 125 of 638 (19.6%) participants with and 657 of 4038 (16.3%) without elevated depressive symptoms had events. Higher risk of MI or death was observed for elevated depressive symptoms after adjusting for demographics (hazard ratio [HR] 1.41, 95% CI 1.15–1.72), but was no longer significant after adjusting for behavioral mechanisms (HR 1.14, 95% CI 0.93–1.40). The four behavioral mechanisms together significantly attenuated the risk for MI or death conveyed by elevated depressive symptoms (−36.9%, 95% CI −18.9 to −119.1%), with smoking (−17.6%, 95% CI −6.5% to −56.0%) and physical inactivity (−21.0%, 95% CI −9.7% to −61.1%) having the biggest explanatory roles.
Our findings suggest potential roles for behavioral interventions targeting smoking and physical inactivity in patients with CHD and comorbid depression.
PMCID: PMC3568239  PMID: 23290548
myocardial infarction; depression; death; physical exercise; smoking
8.  Use of a Disease Risk Score to Compare Serious Infections Associated with Anti-TNF Therapy among High versus Lower Risk Rheumatoid Arthritis Patients 
Arthritis care & research  2013;65(2):235-243.
To evaluate whether rates of serious infection with anti-TNF therapy in rheumatoid arthritis (RA) patients differ in magnitude by specific drugs and patient characteristics.
Among new non-biologic disease modifying anti-rheumatic drug (DMARD) users enrolled in Medicare/Medicaid or a large U.S. commercial health plan, we created and validated a person-specific infection risk score based upon age, demographics, insurance, glucocorticoid dose, and comorbidities to identify patients at high risk for hospitalized infections. We then applied this risk score to new users of infliximab, etanercept, and adalimumab and compared the observed one-year rate of infection to each other and to the predicted infection risk score estimated in the absence of anti-TNF exposure.
Among 11,657 RA patients initiating anti-TNF therapy, the observed one year rate of infection was 14.2 per 100 person-years in older patients (>= 65 years) and 4.8 in younger patients (< 65 years). There was a relatively constant rate difference of 1–4 infections per 100 person-years associated with anti-TNF therapy across the range of the infection risk score. Infliximab had a significantly greater adjusted rate of infection compared to etanercept and adalimumab in both high and lower risk RA patients.
The rate of serious infections for anti-TNF agents was incrementally increased by a fixed absolute difference irrespective of age, comorbidities, and other factors that contributed to infections. Older patients and those with high comorbidity burdens should be reassured that the magnitude of incremental risk with anti-TNF agents is not greater for them than for lower risk patients.
PMCID: PMC3414685  PMID: 22556118
rheumatoid arthritis; infection; anti-TNF; DMARD; prediction
9.  Association between antihypertensive medication adherence and visit-to-visit variability of blood pressure 
It has been hypothesized that high visit-to-visit variability (VVV) of systolic blood pressure (SBP) may be the result of poor antihypertensive medication adherence. We studied this association using data from 1,391 individuals taking antihypertensive medication selected from a large managed care organization. The 8-item Morisky Medication Adherence Scale, administered during three annual surveys, captured self-report adherence with scores <6, 6 to <8 and 8 representing low, medium and high adherence, respectively. The mean (standard deviation [SD]) for SD of SBP across study visits was 12.9 (4.4), 13.5 (4.8), and 14.1 (4.5) mmHg in participants with high, medium and low self-reported adherence, respectively. After multivariable adjustment and compared to those with high self-report adherence, SD of SBP was 0.60 (95% CI: 0.13–1.07) and 1.08 (95% CI: 0.29–1.87) mmHg higher among participants with medium and low self-report adherence, respectively. Results were consistent when pharmacy fill was used to define adherence. These data suggest low antihypertensive medication adherence explains only a small proportion of VVV of SBP.
PMCID: PMC3659162  PMID: 23339729
Medication adherence; blood pressure variability; hypertension
10.  Healthy Behaviors, Risk Factor Control and Awareness of Chronic Kidney Disease 
American journal of nephrology  2013;37(2):135-143.
The association between chronic kidney disease (CKD) awareness and healthy behaviors is unknown. We examined whether CKD self-recognition is associated with healthy behaviors and achieving risk-reduction targets known to decrease risk of cardiovascular morbidity and CKD progression.
CKD awareness, defined as a “yes” response to “Has a doctor or other health professional ever told you that you had kidney disease?”, was examined among adults with CKD (eGFR < 60 ml/min/1.73 m2) who participated in the REasons for Geographic and Racial Differences in Stroke study. Odds of participation in healthy behaviors (tobacco avoidance, avoidance of regular NSAID use, physical activity) and achievement of risk reduction targets (ACEI/ARB use, systolic blood pressure (SBP) control and glycemic control among those with diabetes) among those aware vs. unaware of their CKD were determined by logistic regression, controlling for socio-demographics, access to care and co-morbid conditions. SBP control was defined as < 130 mmHg (primary definition) or < 140 mmHg (secondary definition).
Of 2,615 participants, only 6% (n=166) were aware of having CKD. Those who were aware had 82% higher odds of tobacco avoidance compared to those unaware [adjusted odds ratio =1.82, 95% CI (1.02–3.24)]. CKD awareness was not associated other healthy behaviors or achievement of risk-reduction targets.
Awareness of CKD was only associated with participation in one healthy behavior and was not associated with achievement of risk-reduction targets. To encourage adoption of healthy behaviors, a better understanding of barriers to participation in CKD-healthy behaviors is needed. Keywords: chronic kidney disease, awareness, behaviors, self-management
PMCID: PMC3649001  PMID: 23392070
Chronic kidney disease; awareness; self-management; behaviors
11.  Gender Differences in Calls to 9-1-1 During an Acute Coronary Syndrome 
Calling 9-1-1 during an acute coronary syndrome (ACS) decreases time to treatment and may improve prognosis. Women may have more atypical ACS symptoms compared to men, but few data are available on differences in gender and ACS symptoms in calling 9-1-1. We conducted patient interviews and structured chart reviews to determine gender differences in calling 9-1-1. Calls to 9-1-1 were assessed by self-report and validated by medical chart review. Of the 476 patients studied, 292 (61%) patients were diagnosed with unstable angina (UAP) and 184 (39%) patients were diagnosed with a myocardial infarction (MI). Overall, only 23% of patients called 9-1-1. A similar percentage of women and men with UAP called 9-1-1 (15% and 13%, respectively, P = 0.59). In contrast, women with MI were significantly more likely to call 9-1-1 than men (57% vs. 28%, P < 0.001). After adjustment for sociodemographic factors, health insurance status, history of MI, left ventricular ejection fraction, GRACE score and ACS symptoms, women were 1.79 times more likely to call 9-1-1 during an MI than men (prevalence ratio 1.79; 95% C.I. 1.22 – 2.64, P < 0.01). In conclusion, the findings in the current study suggest that initiatives to increase calls to 9-1-1 are needed for both women and men.
PMCID: PMC3715374  PMID: 23040599
Acute Coronary Syndrome; Gender; Emergency Services
12.  Prevalence of Proteinuria and Elevated Serum Cystatin C among HIV-infected Adolescents in the Reaching for Excellence in Adolescent Care and Health (REACH) Study 
In the United States (US), kidney dysfunction is prevalent in almost 30% of HIV-infected patients and is an independent predictor of mortality. Proteinuria and elevated serum cystatin C (eCysC) are used as markers of kidney disease in the general population; however, the prevalence of these markers in HIV-infected adolescents is largely unknown.
This study includes 304 HIV-infected adolescents from the Reaching for Excellence in Adolescent Care and Health (REACH) cohort, an observational study of adolescents recruited from 13 US cities. Clinical and demographic characteristics of participants were evaluated as correlates of proteinuria, a urine protein to creatinine ratio (UP/Cr) of ≥200 mg/g. Select univariate predictors were assessed to determine the association with urinary protein excretion and serum cystatin C in multivariable linear regression models and proteinuria and elevated serum cystatin C (eCysC ≥ 75th percentile) in multivariable logistic regression models.
Overall, 19.1% of the participants had proteinuria while 23.7% had an eCysC. Low CD4+ T-lymphocyte counts (<200 cells/mm3) were significantly associated with a greater UP/Cr in linear models and with proteinuria in logistic regression models. CD4+ T-lymphocyte counts <500 cells/mm3 were significantly associated with a greater serum cystatin C concentration in linear models and with eCysC in logistic regression models.
Proteinuria among HIV-infected adolescents in REACH was approximately two-fold greater than healthy US adolescents. Both proteinuria and eCysC are associated with CD4+ T-lymphocyte counts. Further studies investigating early markers of kidney disease and the association with immune status and inflammation in adolescents are needed.
PMCID: PMC3494783  PMID: 22918154
HIV; adolescent; kidney; CD4+ T-cells; proteinuria; serum cystatin C
13.  The Contributions of Unhealthy Lifestyle Factors to Apparent Resistant Hypertension: Findings from the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study 
Journal of hypertension  2013;31(2):10.1097/HJH.0b013e32835b6be7.
Unhealthy lifestyle factors may contribute to apparent treatment resistant hypertension (aTRH). We examined associations of unhealthy lifestyle factors with aTRH in individuals taking antihypertensive medications from three or more classes.
Participants (n=2,602) taking three or more antihypertensive medication classes were identified from the population-based REasons for Geographic And Racial Differences in Stroke (REGARDS) study. aTRH was defined as having systolic/diastolic blood pressure ≥140/90 mmHg despite the use of three or more antihypertensive medication classes or the use of four or more classes to achieve blood pressure control. Lifestyle factors included obesity, physical inactivity, current smoking, heavy alcohol consumption, a low DASH diet score and high sodium-to-potassium (Na/K) intake.
Among participants taking three or more antihypertensive medication classes, 1,293 (49.7%) participants had aTRH. The prevalence of unhealthy lifestyle factors in participants with and without aTRH was 55.2% and 51.7% respectively for obesity, 42.2% and 40.5% for physical inactivity, 11.3% and 11.5% for current smoking, 3.1% and 4.0% for heavy alcohol consumption, 23.1% and 21.5% for low DASH diet score, and 25.4% and 24.4% for high Na/K intake. After adjustment for age, sex, race, and geographic region of residence, none of the unhealthy lifestyle factors was associated with aTRH. The associations between each unhealthy lifestyle factor and aTRH remained non-significant after additional adjustment for education, income, depressive symptoms, total calorie intake, and co-morbidities.
Unhealthy lifestyle factors did not have independent associations with aTRH among individuals taking three or more antihypertensive medication classes.
PMCID: PMC3838894  PMID: 23303356
Hypertension; blood pressure; antihypertensive agents; epidemiology
14.  Low Income and Albuminuria Among REGARDS (Reasons for Geographic and Racial Differences in Stroke) Study Participants 
Albuminuria is an important risk factor for progressive CKD and is more prevalent among black than among white adults. We sought to determine the association between low income and albuminuria, and if this association differs for blacks and whites.
Study Design
Cross-sectional study.
Setting & Participants
9,144 black and 13,684 white U.S. adults aged 45 years and older in the population-based REasons for Geographic and Racial Differences in Stroke (REGARDS) study.
Self-reported annual household income category (≥$75,000, 35,000 – $74,999, $20,000 – $34,999, and <$20,000); black and white race.
Outcomes & Measurements
Albuminuria defined as high (30 to 300 mg/g) or very high (>300 mg/g) urinary albumin-creatinine ratio (ACR). Multinomial logistic regression used to examine the race-stratified association between categories of income and albuminuria (normal, high, or very high ACR).
Overall, geometric mean ACR was 10.2 mg/g, and was higher for blacks (11.8 mg/g) than for whites (9.3 mg/g), p <0.001. Lower income was associated with a higher prevalence of albuminuria for both whites and blacks in unadjusted analyses. After adjustment for demographics, lifestyle factors, comorbid illnesses and estimated glomerular filtration rate, there was a trend towards a stronger association between lower income levels and high ACR among blacks [ORs of 1.38 (95% CI, 1.07 – 1.77), 1.36 (95% CI, 1.05 – 1.75), and 1.58 (95% CI, 1.21–2.05), for income levels of $35,000 – $74,999, $20,000 – $34,999, and <$20,000, respectively; reference group is those with income ≥$75,000] compared to whites [ORs of 0.95 (95% CI, 0.81 – 1.12), 0.95 (95% CI, 0.79 – 1.14), and 1.26 (95% CI, 1.02 – 1.55), respectively]; P interaction 0.08 between race and income. Results were similar for very high ACR, and subgroups of participants with diabetes or hypertension.
Cross-sectional design; not all REGARDS participants provided their annual income.
Lower income may be more strongly associated with albuminuria among blacks than among whites, and may be a determinant of racial disparities in albuminuria.
PMCID: PMC3448844  PMID: 22694949
Race; albuminuria; poverty; chronic kidney disease; socioeconomic status; disparity
15.  Blood Pressure Levels and Stroke: J-curve Phenomenon? 
Current Hypertension Reports  2013;15:575-581.
The blood pressure J-curve discussion has been ongoing for more than 30 years, yet there are still questions in need of definitive answers. On one hand, existing antihypertensive therapy studies provide strong evidence for J-curve-shaped relationships between both diastolic and systolic blood pressure and primary outcomes in the general hypertensive patient population, as well as in high-risk populations, including subjects with coronary artery disease, diabetes mellitus, left ventricular hypertrophy, and the elderly. On the other hand, we have very limited data on the relationship between systolic and diastolic blood pressure and stroke prevention. Moreover, it seems that this outcome is more a case of “the lower the better.” Further large, well-designed studies are necessary in order to clarify this issue, especially as existing available studies are observational, and randomized trials either did not have or lost statistical power and were thus inconclusive.
PMCID: PMC3838583  PMID: 24158455
Blood pressure; Cerebrovascular event; Hypertension; J-curve relationship; Stroke
16.  Racial differences in albuminuria, kidney function, and risk of stroke 
Neurology  2012;79(16):1686-1692.
The objective of this study was to examine the joint associations of estimated glomerular filtration rate (eGFR) and urinary albumin excretion with incident stroke in a large national cohort study.
Associations of urinary albumin to creatinine ratio (ACR) and eGFR with incident stroke were examined in 25,310 participants of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a prospective study of black and white US adults ≥45 years of age.
A total of 548 incident strokes were observed over a median of 4.7 years of follow-up. Higher ACR values were associated with lower stroke-free survival in both black and white participants. Among black participants, as compared to an ACR <10 mg/g, the hazard ratios of stroke associated with an ACR of 10–29.99, 30–300, and >300 mg/g were 1.41 (95% confidence interval [CI] 1.01–1.98), 2.10 (95% CI 1.48–2.99), and 2.70 (95% CI 1.58–4.61), respectively, in analyses adjusted for traditional stroke risk factors and eGFR. In contrast, the hazard ratios among white subjects were only modestly elevated and not statistically significant after adjustment for established stroke risk factors. eGFR <60 mL/min/1.73 m2 was not associated with incident stroke in black or white participants after adjustment for established stroke risk factors.
Higher ACR was independently associated with higher risk of stroke in black but not white participants from a national cohort. Elucidating the reasons for these findings may uncover novel mechanisms for persistent racial disparities in stroke.
PMCID: PMC3468778  PMID: 22993285
17.  Prevalence and correlates of low medication adherence in apparent treatment resistant hypertension 
Low medication adherence may explain part of the high prevalence of apparent treatment resistant hypertension (aTRH). We assessed medication adherence and aTRH among 4,026 participants taking ≥ 3 classes of antihypertensive medication in the population-based REGARDS Study using the 4-item Morisky Medication Adherence Scale (MMAS). Low adherence was defined as a MMAS score ≥ 2. Overall, 66% of participants taking ≥ 3 classes of antihypertensive medication had aTRH. Perfect adherence on the MMAS was reported by 67.8% and 70.9% of participants with and without aTRH, respectively. Low adherence was present among 8.1% of participants with aTRH and 5.0% of those without aTRH (p<0.001). Among those with aTRH, female gender, residence outside the US stroke belt or stroke buckle, physical inactivity, elevated depressive symptoms, and a history of coronary heart disease were associated with low adherence. In the current study, a small percentage of participants with aTRH had low adherence.
PMCID: PMC3464920  PMID: 23031147
Hypertension; Treatment Resistant Hypertension; Medication adherence; Risk Factors
18.  Life Events, Coping, and Antihypertensive Medication Adherence Among Older Adults 
American Journal of Epidemiology  2012;176(Suppl 7):S64-S71.
The authors examined the association between life events and antihypertensive medication adherence in older adults and the moderating role of coping. A cross-sectional analysis was conducted by using data (n = 1,817) from the Cohort Study of Medication Adherence among Older Adults (recruitment conducted from August 2006 through September 2007). Life events occurring in the 12 months preceding the study interview were assessed via the Holmes Rahe Social Readjustment Rating Scale (SRRS), and coping levels were assessed via an adapted version of the John Henry Active Coping Scale. Low adherence to antihypertensive medication was defined as scores less than 6 on the 8-item Morisky Medication Adherence Scale (known as “MMAS-8”). Of study participants, 13.2% had low adherence, and 27.2% and 5.0% had medium (150–299) and high (≥300) SRRS scores, respectively. After multivariable adjustment, the odds ratios for low adherence associated with medium and high, versus low, SRRS were 1.50 (95% confidence interval: 1.11, 2.02) and 2.11 (95% confidence interval: 1.24, 3.58), respectively. When multivariable models were stratified by coping level, the association between life events and adherence was evident only among participants with low coping levels.
PMCID: PMC3530357  PMID: 23035146
coping; hypertension; medication adherence; older adults; stress
19.  Aspirin Use Is Associated with an Improved Long-term Survival in an Unselected Population Presenting with Unstable Angina 
Clinical cardiology  2010;33(9):553-558.
The objective of this study is to determine the long-term mortality benefit of aspirin in unselected patients with unstable angina (UA). For that goal, all residents of Olmsted County, Minnesota presenting to local emergency departments with acute chest pain from January 1985 through December 1992 having symptoms consistent with UA were identified through medical records. A total of 1628 patients were identified with UA and were stratified by aspirin use in-hospital and at discharge. Cardiovascular mortality and non-fatal myocardial infarction and stroke were assessed over a median of 7.5 years follow-up, and all-cause mortality data over a median of 16.7 years. The mean age of patients with UA was 65 years, and 60% were men. After a median of 7.5 years follow-up, all-cause and cardiovascular-mortality rates were lower among patients prescribed versus not prescribed aspirin on discharge. There were 949 post-discharge deaths over the median follow-up of 16.7 years. After multivariable adjustment, aspirin use at discharge was associated with a lower long-term mortality (hazard ratio 0.78; 95% CI 0.65 - 0.93). In conclusion, aspirin use at hospital discharge following UA is associated with a reduction in long-term mortality. This long-term study extends prior trial results from select populations to a population-based cohort.
PMCID: PMC3785089  PMID: 20842739
20.  Blood Pressure Indexes and End-Stage Renal Disease Risk in Adults With Chronic Kidney Disease 
American journal of hypertension  2012;25(7):789-796.
Few studies have compared different blood pressure (BP) indexes for end-stage renal disease (ESRD) risk among individuals with chronic kidney disease.
We examined the relationship between systolic BP (SBP), diastolic BP (DBP), pulse pressure (PP) and mean arterial pressure (MAP) and ESRD risk among 2,772 participants with an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 calculated using the Chronic Kidney Disease Epidemiology Collaboration equation in the REasons for the Geographic And Racial Differences in Stroke (REGARDS) study. BP was measured during a baseline study visit between January 2003 and October 2007 with ESRD incidence through August 2009 ascertained via linkage with the United States Renal Data System (n = 138 ESRD cases).
The mean age was 72.1(standard deviation: 8.7) years. After multivariable adjustment for socio-demographic and clinical risk factors including antihypertensive medication use, the hazard ratio (HR) for ESRD associated with one standard deviation higher SBP (18 mm Hg) was 1.67, (95% confidence intervals (CI) 1.43–1.96), DBP (11 mm Hg) was 1.38, (95% CI 1.16–1.63), PP (15 mm Hg) was 1.50, (95% CI 1.27–1.78) and MAP (11 mm Hg) was 1.54, (95% CI 1.32–1.79). Higher levels of SBP remained associated with an increased HR for ESRD after additional adjustment for DBP (1.65, 95% CI: 1.35–2.01), PP (1.73, 95% CI: 1.32–2.26), and MAP (1.61, 95% CI: 1.16–2.23). After adjustment for SBP, the other BP indexes were not significantly associated with incident ESRD.
These data suggest that of several blood pressure indexes including DBP, PP and MAP, SBP may have the strongest association with ESRD incidence among individuals with reduced eGFR.
PMCID: PMC3784349  PMID: 22573012
blood pressure; chronic kidney disease; end-stage renal disease; hypertension; pulse pressure; systolic blood pressure
21.  Association of Race and Sex With Risk of Incident Acute Coronary Heart Disease Events 
It is unknown whether long-standing disparities in incidence of coronary heart disease (CHD) among US blacks and whites persist.
To examine incident CHD by black and white race and by sex.
Prospective cohort study of 24 443 participants without CHD at baseline from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, who resided in the continental United States and were enrolled between 2003 and 2007 with follow-up through December 31, 2009.
Expert-adjudicated total (fatal and nonfatal) CHD, fatal CHD, and nonfatal CHD (definite or probable myocardial infarction [MI]; very small non–ST-elevation MI [NSTEMI] had peak troponin level <0.5 µg/L).
Over a mean (SD) of 4.2 (1.5) years of follow-up, 659 incident CHD events occurred (153 in black men, 138 in black women, 254 in white men, and 114 in white women). Among men, the age-standardized incidence rate per 1000 person-years for total CHD was 9.0 (95% CI, 7.5–10.8) for blacks vs 8.1 (95% CI, 6.9–9.4) for whites; fatal CHD: 4.0 (95% CI, 2.9–5.3) vs 1.9 (95% CI, 1.4–2.6), respectively; and nonfatal CHD: 4.9 (95% CI, 3.8–6.2) vs 6.2 (95% CI, 5.2–7.4). Among women, the age-standardized incidence rate per 1000 person-years for total CHD was 5.0 (95% CI, 4.2–6.1) for blacks vs 3.4 (95% CI, 2.8–4.2) for whites; fatal CHD: 2.0 (95% CI, 1.5–2.7) vs 1.0 (95% CI, 0.7–1.5), respectively; and nonfatal CHD: 2.8 (95% CI, 2.2–3.7) vs 2.2 (95% CI, 1.7–2.9). Age- and region-adjusted hazard ratios for fatal CHD among blacks vs whites was near 2.0 for both men and women and became statistically nonsignificant after multivariable adjustment. The multivariable-adjusted hazard ratio for incident nonfatal CHD for blacks vs whites was 0.68 (95% CI, 0.51–0.91) for men and 0.81 (95% CI, 0.58–1.15) for women. Of the 444 nonfatal CHD events, 139 participants (31.3%) had very small NSTEMIs.
The higher risk of fatal CHD among blacks compared with whites was associated with cardiovascular disease risk factor burden. These relationships may differ by sex.
PMCID: PMC3772637  PMID: 23117777
coronary heart disease; epidemiology; racial disparities; disease incidence; cohort study
22.  Association of Prediabetes and Diabetes With Stroke Symptoms  
Diabetes Care  2012;35(9):1845-1852.
Stroke symptoms among individuals reporting no physician diagnosis of stroke are associated with an increased risk of future stroke. Few studies have assessed whether individuals with diabetes or prediabetes, but no physician diagnosis of stroke, have an increased prevalence of stroke symptoms.
This study included 25,696 individuals aged ≥45 years from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study who reported no history of stroke or transient ischemic attack at baseline (2003–2007). Glucose measurements, medication use, and self-reported physician diagnosis were used to categorize participants into diabetes, prediabetes, or normal glycemia groups. The presence of six stroke symptoms was assessed using a validated questionnaire.
The prevalence of any stroke symptom was higher among participants with diabetes (22.7%) compared with those with prediabetes (15.6%) or normal glycemia (14.9%). In multivariable models, diabetes was associated with any stroke symptom (prevalence odds ratio [POR] 1.28 [95% CI 1.18–1.39]) and two or more stroke symptoms (1.26 [1.12–1.43]) compared with normal glycemia. In analyses of individual stroke symptoms, diabetes was associated with numbness (1.15 [1.03–1.29]), vision loss (1.52 [1.31–1.76]), half-vision loss (1.54 [1.30–1.84]), and lost ability to understand people (1.34 [1.12–1.61]) after multivariable adjustment. No association was present between prediabetes and stroke symptoms.
In this population-based study, almost one in four individuals with diabetes reported stroke symptoms, which suggests that screening for stroke symptoms in diabetes may be warranted.
PMCID: PMC3424995  PMID: 22699292
23.  Prevalence and prognosis of unrecognized myocardial infarctions in chronic kidney disease 
Nephrology Dialysis Transplantation  2011;27(9):3482-3488.
This study makes an important contribution by being one of the first to define the burden of clinically silent myocardial infarctions in the CKD community.
Unrecognized myocardial infarctions (UMIs) are common in the general population but have not been well studied in patients with chronic kidney disease (CKD). The purpose of this study was to determine the prevalence and prognosis for mortality of UMI among adults with CKD.
The current study included 18 864 participants in the population-based REasons for Geographic And Racial Differences in Stroke (REGARDS) study who completed a baseline examination including a 12-lead electrocardiogram (ECG). UMI was defined as the presence of myocardial infarction (MI) by Minnesota ECG classification in the absence of self-reported or recognized MI (RMI). Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation and albuminuria using albumin-to-creatinine ratio from a spot urine sample. All-cause mortality was assessed over a median 4 years of follow-up.
The prevalence of UMI was 4, 6, 6 and 13% among participants with eGFR levels of ≥60, 45–59.9, 30–44.9 and <30 mL/min/1.73m2, respectively, and 4, 5, 7 and 10% among participants with albuminuria levels of <10, 10–29.9, 30–299.9 and ≥300 mg/g, respectively. Compared to those with no MI, the multivariable adjusted hazard ratio for all-cause mortality associated with UMI and RMI was 1.65 [95% confidence interval (CI): 1.09–2.49] and 1.65 (95% CI: 1.20–2.26), respectively, among individuals with an eGFR <60 mL/min/1.73m2 and 1.49 (95% CI: 1.03–2.16) and 1.88 (95% CI: 1.40–2.52) among individuals with albuminuria ≥30 mg/g.
UMIs are common among individuals with an eGFR <60 mL/min/1.73m2 and albuminuria and associated with an increased mortality risk.
PMCID: PMC3433770  PMID: 22167594
chronic kidney disease; coronary artery disease; mortality
24.  Prevalence and Associations of 25-Hydroxyvitamin D Deficiency in US Children: NHANES 2001–2004 
Pediatrics  2009;124(3):e362-e370.
To determine the prevalence of 25-hydroxyvitamin D (25[OH]D) deficiency and associations between 25(OH)D deficiency and cardiovascular risk factors in children and adolescents.
With a nationally representative sample of children aged 1 to 21 years in the National Health and Nutrition Examination Survey 2001–2004 (n = 6275), we measured serum 25(OH)D deficiency and insufficiency (25[OH]D <15 ng/mL and 15–29 ng/mL, respectively) and cardiovascular risk factors.
Overall, 9% of the pediatric population, representing 7.6 million US children and adolescents, were 25(OH)D deficient and 61%, representing 50.8 million US children and adolescents, were 25(OH)D insufficient. Only 4% had taken 400 IU of vitamin D per day for the past 30 days. After multivariable adjustment, those who were older (odds ratio [OR]: 1.16 [95% confidence interval (CI): 1.12 to 1.20] per year of age), girls (OR: 1.9 [1.6 to 2.4]), non-Hispanic black (OR: 21.9 [13.4 to 35.7]) or Mexican-American (OR: 3.5 [1.9 to 6.4]) compared with non-Hispanic white, obese (OR: 1.9 [1.5 to 2.5]), and those who drank milk less than once a week (OR: 2.9 [2.1 to 3.9]) or used >4 hours of television, video, or computers per day (OR: 1.6 [1.1 to 2.3]) were more likely to be 25(OH)D deficient. Those who used vitamin D supplementation were less likely (OR: 0.4 [0.2 to 0.8]) to be 25(OH)D deficient. Also, after multivariable adjustment, 25(OH)D deficiency was associated with elevated parathyroid hormone levels (OR: 3.6; [1.8 to 7.1]), higher systolic blood pressure (OR: 2.24 mm Hg [0.98 to 3.50 mm Hg]), and lower serum calcium (OR: –0.10 mg/dL [–0.15 to –0.04 mg/dL]) and high-density lipoprotein cholesterol (OR: –3.03 mg/dL [–5.02 to –1.04]) levels compared with those with 25(OH)D levels ≥30 ng/mL.
25(OH)D deficiency is common in the general US pediatric population and is associated with adverse cardiovascular risks.
PMCID: PMC3749840  PMID: 19661054
rickets; vitamin D; cardiovascular risk factors; obesity; racial disparities
25.  Association of Family History of ESRD, Prevalent Albuminuria, and Reduced GFR With Incident ESRD 
The contribution of albuminuria to the increased risk of incident end-stage renal disease (ESRD) in individuals with a family history of ESRD has not been well studied.
Study Design
Prospective cohort study.
Study Setting & Participants
We analyzed data for family history of ESRD collected from 19,409 participants of the Renal REGARDS (Reasons for Geographic and Racial Differences in Stroke) cohort study.
Family history of ESRD was ascertained by asking “Has anyone in your immediate family ever been told that he or she had kidney failure? This would be someone who is on or had been on dialysis or someone who had a kidney transplant.”
Study Outcomes
Incidence rate for ESRD.
Morning urine albumin-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). Incident cases of ESRD were identified through the US Renal Data System.
A family history of ESRD was reported by 11.1% of participants. Mean eGFRs for those with and without a family history of ESRD were 87.5 ± 22.2 (SD) and 86.5 ± 19.3 mL/min/1.73 m2, respectively (P = 0.05) and the respective geometric mean ACRs were 12.2 and 9.7 mg/g (P < 0.001). ESRD incidence rates for those with and without a family history of ESRD were 244.3 and 106.1/100,000 person-years, respectively. After adjusting for age, sex, and race, the ESRD HR for those with versus those without a family history of ESRD was 2.13 (95% CI, 1.18-3.83). Adjustment for comorbid conditions and socioeconomic status attenuated this association (HR, 1.82; 95% CI, 1.00-3.28), and further adjustment for baseline eGFR and ACR completely attenuated the association between family history of ESRD and incident ESRD (HR, 1.12; 95% CI, 0.69-1.80).
The report of a family history of ESRD was not validated.
Family history of ESRD is common in older Americans and the increased risk of ESRD associated with a family history reflects lower GFR, higher albuminuria, and comorbid conditions.
PMCID: PMC3725825  PMID: 22078058
Race; albuminuria; end-stage renal disease; chronic kidney disease

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