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1.
Stroke ; : STROKEAHA120030063, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32998653

RESUMO

BACKGROUND AND PURPOSE: Data on the significance of combined white matter hyperintensities (WMH)/lacunar brain infarcts, and their progression over time for the prediction of stroke are scarce. We studied associations between the progression in combined measures of microvascular brain disease and risk of stroke in the ARIC study (Atherosclerosis Risk in Communities). METHODS: Prospective analysis of 907 stroke-free ARIC participants who underwent a brain magnetic resonance imaging (MRI) in 1993 to 1995, a second brain MRI in 2004 to 2006, and were subsequently followed for stroke incidence through December 31, 2017 (median [25%-75%] follow-up 12.6 [8.9-13.4] years). A combined measure of microvascular brain disease was defined at each visit and categorized by progression from first to second brain MRI as no progression; mild progression (increase of ≥1 unit in WMH grade or new lacune), and moderate progression (increase of ≥1 unit in WMH grade and new lacune). All definite/probable ischemic or hemorrhagic incident strokes occurring after this second MRI, and through 2017, were included. Associations between microvascular brain disease, progression in the combined measures, and stroke incidence were studied with Cox proportional hazard models, adjusting for age, sex, race, education level, time from first to second MRI, body mass index, smoking, hypertension, diabetes mellitus, and coronary heart disease. RESULTS: At the second brain MRI (mean age 72), the distribution of the combined measure was 37% WMH grade <2 and no lacune; 57% WMH grade ≥2 or lacune; and 6% WMH grade ≥2 and lacune. No progression in the combined measures was observed in 38% of participants, 57% showed mild progression and 5% showed moderate progression. Sixty-four incident strokes occurred during the follow-up period. Compared with no change in the combined measure, moderate progression of microvascular brain disease was significantly associated with higher risk of stroke (adjusted hazard ratio, 3.00 [95% CI, 1.30-6.94]). CONCLUSIONS: Progression of microvascular brain disease, manifesting as both new lacunes and increase in WMHs grade, is related to substantial increase in long-term risk of stroke.

2.
Atherosclerosis ; 313: 137-143, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33049655

RESUMO

BACKGROUND AND AIMS: We aimed at comprehensively evaluate the independent association of diabetes and its duration with incident abdominal aortic aneurysm (AAA) and aortic diameter. METHODS AND RESULTS: We prospectively studied incident AAA according to baseline glycemic status (diabetes, prediabetes, normal glycemia) in 13,116 ARIC participants (1990-1992) and the time-varying exposure of duration post incident diabetes in 11,675 participants (1987-1989) using Cox models. Additionally, we cross-sectionally explored ultrasound-based abdominal aortic diameter by glycemic status and cumulative duration of diabetes in 4710 participants (2011-2013) using linear regression models. Over ~20 years of follow-up, diabetes (vs. normal glycemia) at baseline was independently associated with lower AAA risk (489 cases) (hazard ratio: 0.71 [95%CI 0.51-0.99]), especially after 10 years (hazard ratio: 0.58 [0.38-0.87]). Prediabetes did not demonstrate an independent association. The inverse association was more evident with longer duration of diabetes (p for trend = 0.045), with 30-50% lower risk in eight years after diabetes diagnosis. The cross-sectional analysis demonstrated smaller aortic diameters with longer duration of diabetes (e.g., -0.76 mm [-1.24, -0.28] in diabetes with 8-12 years) compared to non-diabetes, whereas prediabetes consistently showed nominally greater diameter. CONCLUSIONS: Diabetes, especially with longer duration, but not prediabetes, was independently associated with lower risk of AAA and smaller aortic diameter. Our findings suggest that long lasting clinical hyperglycemia plays an important role in the reduced AAA risk, and the reduced aortic diameter may be a structural mechanism behind this paradoxical association.

3.
J Alzheimers Dis ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33044177

RESUMO

BACKGROUND: Previous studies have suggested that adherence to healthy dietary patterns during late life may be associated with improved cognition. However, few studies have examined the association between healthy dietary patterns during midlife and incident dementia. OBJECTIVE: Our study aimed to determine the association between adherence to healthy dietary patterns at midlife and incident dementia. METHODS: We included 13,630 adults from the Atherosclerosis Risk in Communities (ARIC) Study in our prospective analysis. We used food frequency questionnaire responses to calculate four dietary scores: Healthy Eating Index-2015 (HEI-2015), Alternative Healthy Eating Index-2010 (AHEI-2010), alternate Mediterranean (aMed) diet, and Dietary Approaches to Stop Hypertension (DASH). Participants were followed until the end of 2017 for incident dementia. Cox regression models adjusted for covariates were used to estimate risk of incident dementia by quintile of dietary scores. RESULTS: Over a median of 27 years, there were 2,352 cases of incident dementia documented. Compared with participants in quintile 1 of HEI-2015, participants in quintile 5 (healthiest) had a 14% lower risk of incident dementia (hazard ratio, HR: 0.86, 95% confidence interval, CI: 0.74-0.99). There were no significant associations of incident dementia with the AHEI-2010, aMed, or DASH scores. There were no significant interactions by sex, age, race, education, physical activity, hypertension, or obesity. CONCLUSION: Adherence to the HEI-2015, but not the other dietary scores, during midlife was associated with lower risk of incident dementia. Further research is needed to elucidate whether timing of a healthy diet may influence dementia risk.

4.
Am J Kidney Dis ; 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32979415

RESUMO

RATIONALE & OBJECTIVE: Obesity has been related to risk of chronic kidney disease (CKD). However, the associations of different measures of midlife obesity with long-term kidney function trajectories and whether they differ by sex and race is unknown. STUDY DESIGN: Observational study. SETTING & PARTICIPANTS: 13,496 participants from the ARIC study. PREDICTORS: Midlife obesity status as measured by body mass index (BMI), waist to hip ratio, and predicted percent fat at baseline. OUTCOMES: Estimated glomerular filtration rate (eGFR) calculated using serum creatinine measured at 5 study visits and end-stage kidney disease (ESKD). ANALYTICAL APPROACH: Mixed models with random intercepts and random slopes for eGFR. Cox proportional hazards models for ESKD. RESULTS: Baseline mean age was 54 years, median eGFR was 103 ml/min/1.73 m2, and median BMI was 27 kg/m2. Over 30 years of follow-up, midlife obesity measures were associated with eGFR decline in white and black women but not consistently in men. Adjusted for age, center, smoking and coronary heart disease (CHD), the differences (95% CI) in eGFR decline slope (unit: ml/min per 1.73 m2 per decade) per standard deviation higher BMI, waist to hip ratio, and predicted percent fat were 0.09 (-0.18, 0.36), -0.25 (-0.50, 0.01) and -0.14 (-0.41, 0.13) for white men, -0.91 (-1.15, -0.67), -0.82 (-1.06, -0.58) and -1.02 (-1.26, -0.78) for white women, -0.70 (-1.54, 0.14), -1.60 (-2.42, -0.78) and -1.24 (-2.08, -0.40) for black men, and -1.24 (-2.08, -0.40), -1.50 (-2.05, -0.95) and -1.43 (-2.00, -0.86) for black women. Obesity indicators were independently associated with risk of ESKD for all sex-race groups except white men. LIMITATIONS: Loss to follow-up during three decades of follow-up with five eGFR measurements. CONCLUSIONS: Obesity status is a risk factor for future decline in kidney function and development of ESKD in black and white women with less consistent associations among men.

5.
Genome Med ; 12(1): 84, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32988399

RESUMO

BACKGROUND: Mitochondrial DNA copy number (mtDNA-CN) has been associated with a variety of aging-related diseases, including all-cause mortality. However, the mechanism by which mtDNA-CN influences disease is not currently understood. One such mechanism may be through regulation of nuclear gene expression via the modification of nuclear DNA (nDNA) methylation. METHODS: To investigate this hypothesis, we assessed the relationship between mtDNA-CN and nDNA methylation in 2507 African American (AA) and European American (EA) participants from the Atherosclerosis Risk in Communities (ARIC) study. To validate our findings, we assayed an additional 2528 participants from the Cardiovascular Health Study (CHS) (N = 533) and Framingham Heart Study (FHS) (N = 1995). We further assessed the effect of experimental modification of mtDNA-CN through knockout of TFAM, a regulator of mtDNA replication, via CRISPR-Cas9. RESULTS: Thirty-four independent CpGs were associated with mtDNA-CN at genome-wide significance (P < 5 × 10- 8). Meta-analysis across all cohorts identified six mtDNA-CN-associated CpGs at genome-wide significance (P < 5 × 10- 8). Additionally, over half of these CpGs were associated with phenotypes known to be associated with mtDNA-CN, including coronary heart disease, cardiovascular disease, and mortality. Experimental modification of mtDNA-CN demonstrated that modulation of mtDNA-CN results in changes in nDNA methylation and gene expression of specific CpGs and nearby transcripts. Strikingly, the "neuroactive ligand receptor interaction" KEGG pathway was found to be highly overrepresented in the ARIC cohort (P = 5.24 × 10- 12), as well as the TFAM knockout methylation (P = 4.41 × 10- 4) and expression (P = 4.30 × 10- 4) studies. CONCLUSIONS: These results demonstrate that changes in mtDNA-CN influence nDNA methylation at specific loci and result in differential expression of specific genes that may impact human health and disease via altered cell signaling.

6.
J Am Heart Assoc ; 9(19): e014669, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-32924735

RESUMO

Background Heart failure with preserved ejection fraction (HFpEF) accounts for half of heart failure hospitalizations, with limited data on predictors of mortality by sex and race. We evaluated for differences in predictors of all-cause mortality by sex and race among hospitalized patients with HFpEF in the ARIC (Atherosclerosis Risk in Communities) Community Surveillance Study. Methods and Results Adjudicated HFpEF hospitalization events from 2005 to 2013 were analyzed from the ARIC Community Surveillance Study, comprising 4 US communities. Comparisons between clinical characteristics and mortality at 1 year were made by sex and race. Of 4335 adjudicated acute decompensated heart failure cases, 1892 cases (weighted n=8987) were categorized as HFpEF. Men had an increased risk of 1-year mortality compared with women in adjusted analysis (hazard ratio [HR], 1.27; 95% CI, 1.06-1.52 [P=0.01]). Black participants had lower mortality compared with White participants in unadjusted and adjusted analyses (HR, 0.79; 95% CI, 0.64-0.97 [P=0.02]). Age, heart rate, worsening renal function, and low hemoglobin were associated with increased mortality in all subgroups. Higher body mass index was associated with improved survival in men, with borderline interaction by sex. Higher blood pressure was associated with improved survival among all groups, with significant interaction by race. Conclusions In a diverse HFpEF population, men had worse survival compared with women, and Black participants had improved survival compared with White participants. Age, heart rate, and worsening renal function were associated with increased mortality across all subgroups; high blood pressure was associated with decreased mortality with interaction by race. These insights into sex- and race-based differences in predictors of mortality may help strategize targeted management of HFpEF.

7.
Hypertension ; : HYPERTENSIONAHA12015956, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32981368

RESUMO

Multiple clinical guidelines recommend an ACE (angiotensin-converting enzyme) inhibitor or angiotensin II receptor blocker (ARB) in patients with elevated albuminuria, which can be measured through urine albumin-to-creatinine ratio (ACR), protein-to-creatinine ratio, or dipstick. However, how albuminuria test results relate to the prescription of ACE inhibitor/ARB is uncertain. We identified individuals with an ACR measurement between January 1, 2004, and June 30, 2018, and no contraindications or allergy to ACE inhibitor/ARB. We performed multivariable logistic regression analyses to evaluate the association between ACR level and prescription of ACE inhibitor/ARB within 6 months after the test. We applied similar methods to investigate the association of protein-to-creatinine ratio and dipstick measurement results with the prescription of ACE inhibitor/ARB. Among 67 237 individuals with an ACR measurement, 47.7% were already taking an ACE inhibitor or ARB at the time of first ACR measurement. Among the 35 138 individuals who were not on ACE inhibitor/ARB, those with higher ACR levels were more likely to be prescribed ACE inhibitor/ARB in the following 6 months, with steep increases in prescriptions until ACR 300 mg/g, after which the association plateaued. The majority (80.9%) of ACE inhibitor/ARB prescriptions were made by family medicine and internal medicine. A similar pattern held in the cohorts tested by protein-to-creatinine ratio and dipstick measurement. Our study provides evidence that albuminuria test results change patient care, suggesting that adherence to albuminuria testing is a key step in optimal medical management.

8.
Am J Kidney Dis ; 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32971191

RESUMO

RATIONALE & OBJECTIVE: Physical activity is associated with lower risk of cardiovascular disease, diabetes, and hypertension, which have shared risk factor profiles with chronic kidney disease (CKD). However, there are conflicting findings regarding the relationship between physical activity and CKD. The objective was to evaluate the association between physical activity and CKD development over long-term follow-up using the Atherosclerosis Risk in Communities (ARIC) study. STUDY DESIGN: Prospective cohort study. SETTING: & Participants: 14,537 participants aged 45 to 64 years old. PREDICTORS: Baseline physical activity status was assessed by the modified Baecke Physical Activity Questionnaire at visit 1 (1987-1989) and categorized according to the 2018 Physical Activity Guidelines for Americans to group participants as inactive, insufficiently active, active, and highly active. OUTCOMES: Incident CKD defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 at follow up and ≥25% decline in eGFR relative to baseline, CKD-related hospitalization or death, or end stage renal disease. ANALYTICAL APPROACH: Cox proportional hazards regression. RESULTS: At baseline, 37.8%, 24.2%, 22.7%, and 15.3% of participants were classified as inactive, insufficiently active, active, and highly active, respectively. During a median follow up of 24 years, 33.2% of participants developed CKD. After adjusting for age, sex, race-center, education, smoking status, diet quality, diabetes, coronary heart disease, hypertension, antihypertensive medication, body mass index, and baseline eGFR, higher categories of physical activity were associated with lower risk of CKD compared to the inactive group (HR for insufficiently active, 0.95 [95% CI, 0.88-1.02]; active, 0.93 [95% CI, 0.86-1.01]; highly active, 0.89 [95% CI, 0.81-0.97]; P for trend = 0.007). LIMITATIONS: Observational design and self-reported physical activity that was based on leisure time activity only. Due to low numbers, non black and white participants were excluded. CONCLUSIONS: Highly active participants had a lower risk of developing CKD compared to inactive participants. Index words (5 words): chronic kidney disease; physical activity; Atherosclerosis Risk in Communities Study; estimated glomerular filtration rate; cystatin C.

9.
J Am Geriatr Soc ; 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32894582

RESUMO

BACKGROUND/OBJECTIVES: APOL1 high-risk genotypes confer an increased risk for kidney disease, but their clinical significance among older adults remains unclear. We aimed to determine whether APOL1 genotype status (high risk = 2 risk alleles; low risk = 0-1 risk alleles) and self-reported race (Black; White) are associated with number of hospitalizations, incident chronic kidney disease (CKD), end-stage renal disease (ESRD), and mortality among older adults participating in a community-based cohort study. DESIGN: Observational longitudinal cohort study. SETTING: The Atherosclerosis Risk in Communities (ARIC) study. PARTICIPANTS: Community-dwelling older adults (mean age = 75.8 years; range = 66-90 years). RESULTS: Among 5,564 ARIC participants (78.2% White, 19.1% APOL1 low-risk Black, and 2.7% APOL1 high-risk Black), the proportion with creatinine and cystatin C-based estimated glomerular filtration rate (eGFRCrCys ) below 60 mL/min/1.73 m2 at baseline was 40.6%, 34.8%, and 43.2%, respectively. Over a mean follow-up of 5.1 years, APOL1 high-risk Blacks had a 2.67-fold higher risk for ESRD compared with low-risk Blacks (95% confidence interval [CI] = 1.05-6.79) in models adjusted for age and sex. This association was no longer significant upon further adjustment for baseline eGFRCrCys and albuminuria (hazard ratio [HR] = 1.08; 95% CI = .39-2.96). Rate of hospitalizations and risks of mortality and incident CKD did not differ significantly by APOL1 genotype status. Compared with Whites, Blacks had 1.85-fold and 3.45-fold higher risks for incident CKD and ESRD, respectively, in models adjusted for age, sex, eGFRCrCys , and albuminuria. These associations persisted after additional adjustments for clinical/socioeconomic factors and APOL1 genotype (incident CKD: HR = 1.38; 95% CI = 1.06-1.81; ESRD: HR = 3.20; 95% CI = 1.16-8.86). CONCLUSION: Among older Black adults, APOL1 high-risk genotypes were associated with lower kidney function and therefore higher risk of ESRD. Racial disparities in incident kidney disease persisted in older age and were not fully explained by APOL1.

10.
Kidney Int ; 2020 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-32781106

RESUMO

Although the gold standard of monitoring kidney transplant function relies on glomerular filtration rate (GFR), little is known about GFR trajectories after transplantation, their determinants, and their association with outcomes. To evaluate these parameters we examined kidney transplant recipients receiving care at 15 academic centers. Patients underwent prospective monitoring of estimated GFR (eGFR) measurements, with assessment of clinical, functional, histological and immunological parameters. Additional validation took place in seven randomized controlled trials that included a total of 14,132 patients with 403,497 eGFR measurements. After a median follow-up of 6.5 years, 1,688 patients developed end-stage kidney disease. Using unsupervised latent class mixed models, we identified eight distinct eGFR trajectories. Multinomial regression models identified seven significant determinants of eGFR trajectories including donor age, eGFR, proteinuria, and several significant histological features: graft scarring, graft interstitial inflammation and tubulitis, microcirculation inflammation, and circulating anti-HLA donor specific antibodies. The eGFR trajectories were associated with progression to end stage kidney disease. These trajectories, their determinants and respective associations with end stage kidney disease were similar across cohorts, as well as in diverse clinical scenarios, therapeutic eras and in the seven randomized control trials. Thus, our results provide the basis for a trajectory-based assessment of kidney transplant patients for risk stratification and monitoring.

12.
Mayo Clin Proc ; 95(9): 1928-1939, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32771237

RESUMO

OBJECTIVE: To evaluate whether the incidence of infectious diseases increases the long-term risk for incident end-stage renal disease (ESRD) in the general population. PATIENTS AND METHODS: In 10,290 participants of the Atherosclerosis Risk in Communities Study who attended visit 4 (1996-1998), we evaluated the association of incident hospitalization with major infections (pneumonia, urinary tract infection, bloodstream infection, and cellulitis and osteomyelitis) with subsequent risk for ESRD through September 30, 2015. Hospitalization with major infection was entered into multivariable Cox models as a time-varying exposure to estimate the hazard ratios. RESULTS: Mean age was 63 years, and of 10,290 individuals, 56% (n=5781) were women, 22% (n=2252) were black, and 7% (n=666) had an estimated glomerular filtration rate less than 60 mL/min/1.73 m2. During a median follow-up of 17.4 years, there were 2642 incident hospitalizations with major infection and 281 cases of ESRD (132 cases after hospitalization with major infection). The risk for ESRD was higher following major infection compared with while free of major infection (crude incidence rate, 10.9 vs 1.0 per 1000 person-years). In multivariable time-varying Cox analysis, hospitalization with major infection was associated with a 3.3-fold increased risk for ESRD (hazard ratio, 3.34; 95% CI, 2.56-4.37). The association was similar across pneumonia, urinary tract infection, bloodstream infection, and cellulitis and osteomyelitis, and remained significant across subgroups of age, sex, race, diabetes, history of cardiovascular disease, and chronic kidney disease. CONCLUSION: Hospitalization with major infection was independently and robustly associated with subsequent risk for ESRD. Whether preventive approaches against infection have beneficial effects on kidney outcomes may deserve future investigations.

13.
Am J Kidney Dis ; 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32768632

RESUMO

RATIONALE & OBJECTIVE: Current dietary guidelines recommend that patients with chronic kidney disease (CKD) restrict individual nutrients, such as sodium, potassium, phosphorus, and protein. This approach can be difficult for patients to implement and ignores important nutrient interactions. Dietary patterns are an alternative method to intervene on diet. Our objective was to define the associations of 4 healthy dietary patterns with risk for CKD progression and all-cause mortality among people with CKD. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 2,403 participants aged 21 to 74 years with estimated glomerular filtration rates of 20 to 70mL/min/1.73m2 and dietary data in the Chronic Renal Insufficiency Cohort (CRIC) Study. EXPOSURES: Healthy Eating Index-2015, Alternative Healthy Eating Index-2010, alternate Mediterranean diet (aMed), and Dietary Approaches to Stop Hypertension (DASH) diet scores were calculated from food frequency questionnaires. OUTCOMES: (1) CKD progression defined as≥50% estimated glomerular filtration rate decline, kidney transplantation, or dialysis and (2) all-cause mortality. ANALYTICAL APPROACH: Cox proportional hazards regression models adjusted for demographic, lifestyle, and clinical covariates to estimate hazard ratios (HRs) and 95% CIs. RESULTS: There were 855 cases of CKD progression and 773 deaths during a maximum of 14 years. Compared with participants with the lowest adherence, the most highly adherent tertile of Alternative Healthy Eating Index-2010, aMed, and DASH had lower adjusted risk for CKD progression, with the strongest results for aMed (HR, 0.75; 95% CI, 0.62-0.90). Compared with participants with the lowest adherence, the highest adherence tertiles for all scores had lower adjusted risk for all-cause mortality for each index (24%-31% lower risk). LIMITATIONS: Self-reported dietary intake. CONCLUSIONS: Greater adherence to several healthy dietary patterns is associated with lower risk for CKD progression and all-cause mortality among people with CKD. Guidance to adopt healthy dietary patterns can be considered as a strategy for managing CKD.

15.
Hypertension ; 76(3): 699-706, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32713275

RESUMO

The 2017 American College of Cardiology/American Heart Association guideline defines hypertension as a blood pressure ≥130/80 mm Hg, whereas the 2018 European Society of Cardiology (ESC) and 2019 National Institute for Health and Care Excellence (NICE) guidelines use a ≥140/90 mm Hg threshold. Our objective was to study the associations between isolated diastolic hypertension (IDH), diagnosed using these 2 blood pressure thresholds, and cardiovascular disease (CVD) in a large cohort of UK adults. We analyzed data from UK Biobank, which enrolled participants between 2006 and 2010 with follow-up through March 2019. We excluded persons with systolic hypertension or baseline CVD. We defined incident CVD as a composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. We used Cox regression to quantify associations between IDH and CVD, as well as the individual outcomes included in the composite outcome. We studied 151 831 participants with normal systolic blood pressure (mean age 54 years, 40% male). Overall, 24.5% had IDH by the American College of Cardiology/American Heart Association definition compared with 6% by the ESC/NICE definition. Compared with normal diastolic blood pressure, IDH by the American College of Cardiology/American Heart Association definition was not significantly associated with CVD risk (hazard ratio, 1.08 [95% CI, 0.98-1.18]) whereas IDH by the ESC/NICE definition was significantly associated with a modest increase in CVD (hazard ratio, 1.15 [95% CI, 1.04-1.29]). Similar results were found by sex and among participants not taking baseline antihypertensives. Furthermore, neither IDH definition was associated with the individual outcomes of nonfatal myocardial infarction or stroke. In conclusion, the proportion of UK Biobank participants with IDH was significantly higher by the American College of Cardiology/American Heart Association definition compared with the ESC/NICE definitions; however, only the ESC/NICE definition was statistically associated with increased CVD risk.

16.
Eur J Heart Fail ; 2020 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-32683762

RESUMO

AIMS: The cardiorenal syndrome refers to a bidirectional relationship between the kidney and the heart. However, epidemiological evidence of cardiovascular disease (CVD) as a risk factor for chronic kidney disease (CKD) progression is actually scarce. METHODS AND RESULTS: We examined the slopes of estimated glomerular filtration rate (eGFR) decline in the 2 years before vs. after an incident hospitalization with heart failure (HF) (n = 20 420), coronary heart disease (CHD) (n = 18 152), or stroke (n = 1808) using data from a complete laboratory data collection in Stockholm, Sweden between 2006 and 2011. eGFR slopes were estimated using mixed-effect models with unstructured residual correlation. Overall, incident hospitalization with HF and CHD, but not stroke, was significantly associated with a subsequent accelerated decline in eGFR, with a faster eGFR decline and greater slope change after HF than CHD. The pre-event vs. post-event eGFR slopes (mL/min/1.73 m2 per year) were -1.67 (-1.77 to -1.57) vs. -2.76 (-2.82 to -2.71), with a Δslope of -1.09 (-1.16 to -1.02) for HF; -1.09 (-1.20 to -0.98) vs. -1.87 (-1.92 to -1.81), with a Δslope of -0.78 (-0.85 to -0.70) for CHD; and -1.00 (-1.37 to -0.63) vs. -0.99 (-1.19 to -0.78), with a Δslope of 0.02 (-0.24 to 0.27) for stroke. The accelerated declines in eGFR after HF and CHD were consistent across the spectrum of eGFR, although pre-event eGFR slopes were steeper in lower eGFR (e.g. pre-event eGFR slope for HF -0.64 (-0.76 to -0.53) for eGFR ≥60 mL/min/1.73 m2 , -1.43 (-1.57 to -1.30) for eGFR 30-59 mL/min/1.73 m2 , and -2.42 (-2.71 to -2.12) for eGFR <30 mL/min/1.73 m2 ). CONCLUSIONS: Incident hospitalization with cardiac diseases (i.e. HF and CHD) was significantly associated with a subsequent acceleration of eGFR decline.

17.
Ann Intern Med ; 173(6): 426-435, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32658569

RESUMO

BACKGROUND: Although measuring albuminuria is the preferred method for defining and staging chronic kidney disease (CKD), total urine protein or dipstick protein is often measured instead. OBJECTIVE: To develop equations for converting urine protein-creatinine ratio (PCR) and dipstick protein to urine albumin-creatinine ratio (ACR) and to test their diagnostic accuracy in CKD screening and staging. DESIGN: Individual participant-based meta-analysis. SETTING: 12 research and 21 clinical cohorts. PARTICIPANTS: 919 383 adults with same-day measures of ACR and PCR or dipstick protein. MEASUREMENTS: Equations to convert urine PCR and dipstick protein to ACR were developed and tested for purposes of CKD screening (ACR ≥30 mg/g) and staging (stage A2: ACR of 30 to 299 mg/g; stage A3: ACR ≥300 mg/g). RESULTS: Median ACR was 14 mg/g (25th to 75th percentile of cohorts, 5 to 25 mg/g). The association between PCR and ACR was inconsistent for PCR values less than 50 mg/g. For higher PCR values, the PCR conversion equations demonstrated moderate sensitivity (91%, 75%, and 87%) and specificity (87%, 89%, and 98%) for screening (ACR >30 mg/g) and classification into stages A2 and A3, respectively. Urine dipstick categories of trace or greater, trace to +, and ++ for screening for ACR values greater than 30 mg/g and classification into stages A2 and A3, respectively, had moderate sensitivity (62%, 36%, and 78%) and high specificity (88%, 88%, and 98%). For individual risk prediction, the estimated 2-year 4-variable kidney failure risk equation using predicted ACR from PCR had discrimination similar to that of using observed ACR. LIMITATION: Diverse methods of ACR and PCR quantification were used; measurements were not always performed in the same urine sample. CONCLUSION: Urine ACR is the preferred measure of albuminuria; however, if ACR is not available, predicted ACR from PCR or urine dipstick protein may help in CKD screening, staging, and prognosis. PRIMARY FUNDING SOURCE: National Institute of Diabetes and Digestive and Kidney Diseases and National Kidney Foundation.

18.
Diabetes Care ; 43(9): 2060-2065, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32611607

RESUMO

OBJECTIVE: Hypoglycemia has been postulated to contribute to falls risk in older adults with type 2 diabetes. However, few studies have prospectively examined the association between severe hypoglycemia and falls, both important causes of morbidity and mortality. RESEARCH DESIGN AND METHODS: We conducted a prospective cohort analysis of participants from the Atherosclerosis Risk in Communities (ARIC) study with diagnosed diabetes at visit 4 (1996-1998). Episodes of severe hypoglycemia requiring medical treatment were identified using ICD-9 codes from hospitalizations, emergency department visits, and ambulance calls; total falls were identified from medical claims using E-codes from 1996 to 2013. Secondary analyses examined hospitalized falls and falls with fracture. We calculated incidence rates and used Cox regression models to evaluate the independent association of severe hypoglycemia with falls occurring after visit 4 through 2013. RESULTS: Among 1,162 participants with diabetes, 149 ever had a severe hypoglycemic event before baseline or during the median of 13.1 years of follow-up. The crude incidence rate of falls among persons without severe hypoglycemia was 2.17 per 100 person-years (PY) (95% CI 1.93-2.44) compared with 8.81 per 100 PY (6.73-11.53) with severe hypoglycemia. After adjustment, severe hypoglycemia was associated with a more than twofold higher risk of falls (hazard ratio 2.23, 95% CI 1.61-3.07). Associations were consistent in subgroups defined by age, sex, race, BMI, duration of diabetes, or functional difficulty. CONCLUSIONS: Severe hypoglycemia was associated with a substantially higher risk of falls in this community-based population of adults with diabetes. Fall risk should be considered when individualizing glycemic treatment in older adults. Assessing hypoglycemia history and future hypoglycemia risk could also improve multifactorial fall prevention interventions for older adults with diabetes.

19.
J Am Soc Nephrol ; 31(8): 1847-1858, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32660971

RESUMO

BACKGROUND: In 2016, the Food and Drug Administration (FDA) changed labeling regarding metformin contraindications in patients with diabetes and CKD from using serum creatinine-based thresholds to using eGFR-based thresholds. Because race and sex affect serum creatinine levels independently of GFR, the earlier creatinine-based contraindication may have inadvertently caused racial and sex disparities in metformin prescription among patients with low eGFR. METHODS: In an analysis of 15,946 Black and White primary care patients with diabetes and eGFR≥30 ml/min per 1.73 m2 in a large health system (the primary cohort), we assessed the association of race and sex with metformin prescription across eGFR level before and after the FDA label change. For a replication cohort, we meta-analyzed data from 36 cohorts with 1,051,723 patients from OptumLabs Data Warehouse. RESULTS: In the primary cohort, before the label change, Black patients with eGFR of 30-44 ml/min per 1.73 m2 were prescribed metformin less often than White counterparts (adjusted prevalence ratio [aPR], 0.65; 95% confidence interval [95% CI], 0.52 to 0.82); this disparity was significantly attenuated after the label change (aPR, 0.90; 95% CI, 0.74 to 1.09; P value for interaction by period =0.04). Results were consistent in the replication cohorts. Men with eGFR of 30-44 ml/min per 1.73 m2 received metformin prescriptions less often than women counterparts before the label change; this was nonsignificantly attenuated after the label change, but we found significant attenuation in the replication cohorts (aPRpre-label change, 0.76; 95% CI, 0.73 to 0.79; aPRpost-label change, 0.85; 95% CI, 0.83 to 0.88; P value for interaction by period <0.001). CONCLUSIONS: The metformin label change to an eGFR-based contraindication may have reduced racial and sex disparities in metformin prescription in moderate kidney dysfunction.

20.
Arterioscler Thromb Vasc Biol ; 40(9): 2322-2331, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32698688

RESUMO

OBJECTIVE: Inflammatory markers, such as hs-CRP (high-sensitivity C-reactive protein), have been reported to be related to peripheral artery disease (PAD). Galectin-3, a biomarker of fibrosis, has been linked to vascular remodeling and atherogenesis. However, its prospective association with incident PAD is unknown; as is the influence of inflammation on the association between galectin-3 and PAD. Approach and Results: In 9851 Atherosclerosis Risk in Communities Study participants free of PAD at baseline (1996-1998), we quantified the association of galactin-3 and hs-CRP with incident PAD (hospitalizations with PAD diagnosis [International Classification of Diseases-Ninth Revision: 440.2-440.4] or leg revascularization [eg, International Classification of Diseases-Ninth Revision: 38.18]) as well as its severe form, critical limb ischemia (PAD cases with resting pain, ulcer, gangrene, or leg amputation) using Cox models. Over a median follow-up of 17.4 years, there were 316 cases of PAD including 119 critical limb ischemia cases. Log-transformed galectin-3 was associated with incident PAD (adjusted hazard ratio, 1.17 [1.05-1.31] per 1 SD increment) and critical limb ischemia (1.25 [1.05-1.49] per 1 SD increment). The association was slightly attenuated after further adjusting for hs-CRP (1.14 [1.02-1.27] and 1.22 [1.02-1.45], respectively). Log-transformed hs-CRP demonstrated robust associations with PAD and critical limb ischemia even after adjusting for galectin-3 (adjusted hazard ratio per 1 SD increment 1.34 [1.18-1.52] and 1.34 [1.09-1.65], respectively). The addition of galectin-3 and hs-CRP to traditional atherosclerotic predictors (C statistic of the base model 0.843 [0.815-0.871]) improved the risk prediction of PAD (ΔC statistics, 0.011 [0.002-0.020]). CONCLUSIONS: Galectin-3 and hs-CRP were independently associated with incident PAD in the general population, supporting the involvement of fibrosis and inflammation in the pathophysiology of PAD.


Assuntos
Proteína C-Reativa/análise , Galectina 3/sangue , Mediadores da Inflamação/sangue , Claudicação Intermitente/sangue , Isquemia/sangue , Doença Arterial Periférica/sangue , Idoso , Biomarcadores/sangue , Estado Terminal , Feminino , Fibrose , Humanos , Incidência , Claudicação Intermitente/diagnóstico , Claudicação Intermitente/epidemiologia , Claudicação Intermitente/terapia , Isquemia/diagnóstico , Isquemia/epidemiologia , Isquemia/terapia , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/epidemiologia , Doença Arterial Periférica/terapia , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Estados Unidos
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