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Polypharmacy and mortality association by chronic kidney disease status: The REasons for Geographic And Racial Differences in Stroke Study.

ABSTRACT: Many Americans take multiple medications simultaneously (polypharmacy). Polypharmacy's effects on mortality are uncertain. We endeavored to assess the association between polypharmacy and mortality in a large U.S. cohort and examine potential effect modification by chronic kidney disease (CKD) status. The REasons for Geographic And Racial Differences in Stroke cohort data (n = 29 627, comprised of U.S. black and white adults) were used. During a baseline home visit, pill bottle inspections ascertained medications used in the previous 2 weeks. Polypharmacy status (major [≥8 ingredients], minor [6-7 ingredients], and none [0-5 ingredients]) was determined by counting the total number of generic ingredients. Cox models (time-on-study and age-time-scale methods) assessed the association between polypharmacy and mortality. Alternative models examined confounding by indication and possible effect modification by CKD. Over 4.9 years median follow-up, 2538 deaths were observed. Major polypharmacy was associated with increased mortality in all models, with hazard ratios and 95% confidence intervals ranging from 1.22 (1.07-1.40) to 2.35 (2.15-2.56), with weaker associations in more adjusted models. Minor polypharmacy was associated with mortality in some, but not all, models. The polypharmacy-mortality association did not differ by CKD status. While residual confounding by indication cannot be excluded, in this large American cohort, major polypharmacy was consistently associated with mortality.

SUBMITTER: Cashion W

PROVIDER: S-EPMC8328192 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Kidney function, albuminuria, and all-cause mortality in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study.

Project description:Chronic kidney disease and albuminuria are associated with increased risk of all-cause mortality.Prospective observational cohort study.17,393 participants (mean age, 64.3 ± 9.6 years) in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) Study.Estimated glomerular filtration rate (eGFR), urinary albumin-creatinine ratio (ACR).All-cause mortality (710 deaths); median duration of follow-up, 3.6 years. MEASUREMENTS & ANALYSIS: Categories of eGFR (90 to <120, 60 to <90, 45 to <60, 30 to <45, and 15 to <30 mL/min/1.73 m(2)) and urinary ACR (<10 mg/g or normal, 10 to <30 mg/g or high normal, 30 to 300 mg/g or high, and >300 mg/g or very high). Cox proportional hazards models were adjusted for demographic factors, cardiovascular covariates, and hemoglobin level.The background all-cause mortality rate for participants with normal ACR, eGFR of 90 to <120 mL/min/1.73 m(2), and no coronary heart disease was 4.3 deaths/1,000 person-years. Higher ACR was associated with an increased multivariable-adjusted HR for all-cause mortality within each eGFR category. Decreased eGFR was associated with a higher adjusted HR for all-cause mortality for participants with high-normal (P = 0.01) and high (P < 0.001) ACRs, but not those with normal or very high ACRs.Only 1 laboratory assessment for serum creatinine and ACR was available.Increased albuminuria was an independent risk factor for all-cause mortality. Decreased eGFR was associated with increased mortality risk in those with high-normal and high ACRs. The mortality rate was low in the normal-ACR group and increased in the very-high-ACR group, but did not vary with eGFR in these groups.

| S-EPMC2963678 | biostudies-literature

Incidence of stroke symptoms among adults with chronic kidney disease: results from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study.

Project description:BackgroundReduced glomerular filtration rate and albuminuria are associated with an increased risk for stroke. Their association with stroke symptoms is not known.MethodsThe incidence of stroke symptoms was determined in 20?386 participants ?45 years of age in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study who were free of a history of stroke, transient ischemic attack and stroke symptoms at baseline. Six stroke symptoms were assessed via telephone interviews at baseline and every 6 months. Participants were followed over a median of 2.1 years (maximum follow-up of 6 years). Estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI equation and the albumin-to-creatinine ratio from spot urine samples.ResultsThe incidence of any stroke symptom (n = 2548 cases) was 10.8, 12.9, 18.2 and 20.7% among participants with an eGFR ?90, 60-89, 45-59 and <45 mL/min/1.73m(2), respectively, and 10.8, 14.4, 17.0 and 18.8 for participants with albumin-to-creatinine ratios <10, 10-29, 30-299 and ?300 mg/g, respectively (each P-trend < 0.001). The multivariable-adjusted hazard ratio (95% confidence interval) for any stroke symptom was 1.02 (0.91-1.14), 1.22 (1.01-1.48) and 1.26 (0.98-1.62) for those with an eGFR of 60-89, 45-59 and <45 mL/min/1.73m(2), respectively, versus ?90 mL/min/1.73m(2) (P-trend = 0.022) and 1.16 (1.03-1.31), 1.29 (1.12-1.50) and 1.11 (0.82-1.49) for those with albumin-to-creatinine ratios of 10-29, 30-299 and ?300 versus <10 mg/g, respectively (P-trend = 0.005).ConclusionsReduced eGFR and higher albuminuria levels are associated with an increased risk for incident stroke symptoms.

| S-EPMC3350340 | biostudies-literature

Self-Reported Stroke Risk Stratification: Reasons for Geographic and Racial Differences in Stroke Study.

Project description:Background and purposeThe standard for stroke risk stratification is the Framingham Stroke Risk Function (FSRF), an equation requiring an examination for blood pressure assessment, venipuncture for glucose assessment, and ECG to determine atrial fibrillation and heart disease. We assess a self-reported stroke risk function (SRSRF) to stratify stroke risk in comparison to the FSRF.MethodsParticipants from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke) were evaluated at baseline and followed for incident stroke. The FSRF was calculated using directly assessed stroke risk factors. The SRSRF was calculated from 13 self-reported questions to exclude those with prevalent stroke and assess stroke risk. Proportional hazards analysis was used to assess incident stroke risk using the FSRF and SRSRF.ResultsOver an average 8.2-year follow-up, 939 of 23 983 participants had a stroke. The FSRF and SRSRF produced highly correlated risk scores (rSpearman=0.852; 95% confidence interval, 0.849-0.856); however, the SRSRF had higher discrimination of stroke risk than the FSRF (cSRSRF=0.7266; 95% confidence interval, 0.7076-0.7457; cFSRF=0.7075; 95% confidence interval, 0.6877-0.7273; P=0.0038). The 10-year stroke risk in the highest decile of predicted risk was 11.1% for the FSRF and 13.4% for the SRSRF.ConclusionsA simple self-reported questionnaire can be used to identify those at high risk for stroke better than the gold standard FSRF. This instrument can be used clinically to easily identify individuals at high risk for stroke and also scientifically to identify a subpopulation enriched for stroke risk.

| S-EPMC5493147 | biostudies-literature

Nondisease-specific problems and all-cause mortality in the REasons for Geographic and Racial Differences in Stroke study.

Project description:To evaluate the association between six nondisease-specific problems (problems that cross multiple domains of health) and mortality in middle-aged and older adults.Prospective, observational cohort.U.S. population sample.Participants included 23,669 black and white U.S. adults aged 45 and older enrolled in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study.Nondisease-specific problems included cognitive impairment, depressive symptoms, exhaustion, falls, impaired mobility, and polypharmacy. Age-stratified (<65, 65-74, ? 75) hazard ratios for all-cause mortality were calculated for each problem individually and according to number of problems.One or more nondisease-specific problems occurred in 40% of participants younger than 65, 45% of those aged 65 to 74, and 55% of those aged 75 and older. Compared with participants with none of these problems, the multivariable adjusted hazard ratio for all-cause mortality associated with each additional nondisease-specific problem was 1.34 (95% confidence interval (CI) = 1.23-1.46) for participants younger than 65, 1.24 (95% CI = 1.15-1.35) for those aged 65 to 74, and 1.30 (95% CI = 1.21-1.39) for those aged 75 and older.Nondisease-specific problems were associated with mortality across a wide age spectrum. Future studies should explore whether treating these problems will improve survival and identify innovative healthcare models to address multiple nondisease-specific problems simultaneously.

| S-EPMC3656135 | biostudies-literature

REGARDS: Reasons for Geographic and Racial Differences in Stroke Cardiorenal GWAS

Project description:REGARDS: Reasons for Geographic and Racial Differences in Stroke Cardiorenal GWAS

| PRJNA786046 | ENA

REGARDS: Reasons for Geographic and Racial Differences in Stroke Cardiorenal GWAS

Project description:REGARDS: Reasons for Geographic and Racial Differences in Stroke Cardiorenal GWAS

| PRJNA786045 | ENA

Racial differences in the association of insulin resistance with stroke risk: the REasons for Geographic And Racial Differences in Stroke (REGARDS) study.

Project description:Insulin resistance is associated with increased stroke risk, but the effect has not been adequately examined separately in white and black populations.The association of baseline insulin resistance with risk of cerebral infarction (CI) and intracerebral hemorrhage (ICH) was assessed in 12 366 white and 6782 black participants from the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort, recruited between 2003 and 2007 and followed for an average of 5.7 years. Insulin resistance was measured with the homeostasis model assessment-insulin resistance.There were 364 incident CI and 41 incident ICH events. The risk for CI increased with the log of insulin resistance in whites (hazards ratio [HR]ln(IR)=1.17; 95% confidence interval [CI], 1.00-1.38) but was largely attenuated by adjustment for stroke risk factors (HRln(IR)=1.05; 95% CI, 0.88-1.26). There was no association in blacks (HRln(IR)=1.01; 95% CI, 0.81-1.25). After adjustment for demographic factors and risk factors, there was a significant difference by race in the association of insulin resistance with risk of ICH (P=0.07), with a decrease in the risk of ICH in whites (HRln(IR)=0.61; 95% CI, 0.35-1.04) but a nonsignificant increase in blacks (HRln(IR)=1.20; 95% CI, 0.60-2.39).These data support the growing evidence that insulin resistance may play a more important role in stroke risk among white than black individuals and suggest a potentially discordant relationship of insulin resistance on CI and ICH among whites.

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Racial Differences in the Association between Parity and Incident Stroke: Results from the REasons for Geographic and Racial Differences in Stroke Study.

Project description:BackgroundCirculatory and vascular changes across consecutive pregnancies may increase the risk of later-life cerebrovascular health outcomes.MethodsThe association between parity and incident stroke was assessed among 7674 white and 6280 black women, aged 45 years and older, and enrolled in the REasons for Geographic and Racial Differences in Stroke Study from 2003 to 2007. Parity was assessed at baseline, and incident stroke was ascertained from physician-adjudicated medical records through September 2014. Cox proportional hazards models were used to estimate hazard ratios (HR) for the association between parity and stroke, adjusting for baseline measures.ResultsAt baseline, 12.7% of white women and 16.2% of black women reported 1 live birth, while 8.2% and 19.0%, respectively, reported 5 or more live births. Mean follow-up time was 7.5 years (standard deviation = 2.8); there were 447 incident strokes. A significant interaction between race and parity was detected (P = .05). Among white women, those with 5 or more live births had a higher stroke risk than those with 1 live birth (HR = 1.57; 95% confidence interval [CI] .93-2.65). However, the association was eliminated after adjustment for baseline characteristics (HR = 1.00, 95% CI .59-1.71). For black women, those with 5 or more live births had the highest stroke risk compared with those with 1 live birth (HR = 1.91, 95% CI 1.25-2.93), but the association was attenuated and no longer statistically significant after adjustment for confounders (HR = 1.40, 95% CI .89-2.18).ConclusionsIn adjusted models, no statistically significantassociations were observed between parity and stroke risk in a diverse cohort of U.S. women. Further studies are needed to elucidate the role of lifestyle and psychosocial factors in the race-specific associations that were observed.

| S-EPMC5362279 | biostudies-literature

Inflammation biomarkers and risk of all-cause mortality in the Reasons for Geographic And Racial Differences in Stroke cohort.

Project description:Inflammation biomarkers, including higher high-sensitivity C-reactive protein (hsCRP) levels, higher white blood cell (WBC) counts, and lower serum albumin levels, are associated with an increased risk of all-cause mortality. Many studies have examined these biomarkers individually, but less is known about their joint association with mortality. hsCRP, WBC count, and serum albumin were measured at baseline in the Reasons for Geographic and Racial Differences in Stroke Study cohort members, who were enrolled in 2003-2007. Over 4.5 years, there were 1,062 deaths in 17,845 participants. High-risk categories were defined as hsCRP or WBC levels above the 75th percentile (5.1 mg/L and 6.9 × 10(9) cells/L, respectively) and albumin levels below the 25th percentile (4.00 g/dL). The authors derived 4 groups that corresponded to 0 (n = 8,341), 1 (n = 6,277), 2 (n = 2,635), or 3 (n = 592) biomarkers in the high-risk category. After adjustment for age, sex, waist circumference, race, region, smoking, alcohol use, income, educational level, physical activity frequency, and medical history and compared with those with no biomarkers in the high-risk category, the hazard ratios for all-cause mortality for 1, 2, and 3 biomarkers in the high-risk category were 1.56 (95% confidence interval: 1.33, 1.82), 2.19 (95% confidence interval: 1.84, 2.62), and 2.96 (95% confidence interval: 2.30, 3.80), respectively (P(trend) < 0.0001). Adding the 3 inflammation biomarkers to a fully adjusted model improved risk discrimination by 23.7% (95% confidence interval: 9.3, 39.9). Measurement of more than 1 biomarker is more useful in risk prediction than single biomarkers.

| S-EPMC3202158 | biostudies-literature

Physical health composite and risk of cancer mortality in the REasons for Geographic and Racial Differences in Stroke Study.

Project description:It is unclear how resting myocardial workload, as indexed by baseline measures of rate-pressure product (RPP) and physical activity (PA), is associated with the overall risk of cancer mortality. We performed prospective analyses among 28,810 men and women from the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. We used a novel physical health (PH) composite index and categorized participants into one of four groups based on combinations from self-reported PA and RPP: 1) No PA and High RPP; 2) No PA and Low RPP; 3) Yes PA and High RPP; and 4) Yes PA and Low RPP. We examined the association between baseline PH composite and cancer mortality adjusted for potential confounders using Cox regression. A total of 1191 cancer deaths were observed over the 10-year observation period, with the majority being lung (26.87%) and gastrointestinal (21.49%) cancers. Even after controlling for sociodemographics, health behaviors, baseline comorbidity score, and medications, participants with No PA and High RPP had 71% greater risk of cancer mortality when compared to participants with PA and Low RPP (adjusted HR: 1.71, 95% CI: 1.42-2.06). These associations persisted after examining BMI, smoking, income, and gender as effect modifiers and all-cause mortality as a competing risk. Poorer physical health composite, including the novel RPP metric, was associated with a nearly 2-fold long-term risk of cancer mortality. The physical health composite has important public health implications as it provides a measure of risk beyond traditional measure of obesity and physical activity.

| S-EPMC7048236 | biostudies-literature

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