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Josef Coresh

Publications and source records attributed to Josef Coresh.

At least 19 recordsLinked to original sources
PubMed2026

Proteomics Analysis of Plasma for Risk of Sepsis: Findings from the Atherosclerosis Risk in Communities Study.

BACKGROUND: Sepsis is a life-threatening complication of infection with high mortality. A high-throughput analysis of circulating blood proteins may provide mechanistic insight and potent therapeutic targets for the prevention of sepsis. METHODS: We used multivariable Cox regression analysis to examine the association of 4955 plasma proteins, measured by SomaScan, with the risk of incident sepsis among 11 065 participants of the Atherosclerosis Risk in Communities (ARIC) Study (visit 3 in 1993 to 1995; mean age, 60.1 years, 54.4% female, 21.0% Black). Proteins (false discovery rate [FDR] of P < 0.05) discovered at visit 3 were replicated using data at visit 5 (n = 4869 in 2011 to 2013: mean age, 75.5 years) and in the Cardiovascular Health Study (CHS) (n = 3512 in 1992 to 1993; mean age, 74.5 years). Canonical pathways were identified by enrichment analyses. RESULTS: At ARIC visit three, 669 proteins were associated with the risk of sepsis; 175 were replicated at visit 5. Of these, 90 were validated in the CHS. The top 20 proteins ranked by P value were relevant to acute inflammatory signaling in innate immunity. Pathway analyses implicated activation of pro-inflammatory pathways (e.g., cytokine storm signaling) as well as inhibition of anti-inflammatory pathways (e.g., liver X receptor/retinoid X receptor [LXR/RXR] activation), which also play relevant roles in lipid metabolism. CONCLUSIONS: In this analysis, levels of acute inflammatory proteins measured during routine visits were associated with the subsequent incidence of sepsis. An increased risk of sepsis associated with the inhibition of anti-inflammatory pathways, such as LXR/RXR warrants further mechanistic investigation.

Humans↗
PubMed2026

Plasma proteomics and incident coronary heart disease.

BACKGROUND: Systematic profiling of plasma proteins in population studies offers a complementary approach to discovery of novel risk factors and may provide new insights into the causes of coronary heart disease. METHODS: To explore relationships between the circulating proteome and coronary heart disease (CHD), we evaluated associations of 4780 plasma proteins with incident CHD&#xa0;in the Cardiovascular Health Study (CHS, N=2856,&#xa0;575&#xa0;CHD events) and replicated significant associations in the Atherosclerosis Risk in Communities Study (ARIC, N&#x2009;=&#x2009;10456; 1375 events). RESULTS: We find that 11 proteins significantly associate with incident CHD after adjusting for risk factors; and eight significantly replicated in ARIC. Several proteins correlate with carotid intimal medial thickness and CHD associations are attenuated in participants without subclinical atherosclerosis. Macrophage metalloelastase (MMP12) is the strongest observed association (Hazard Ratio, 1.31; 95% Confidence Interval, 1.19-1.44). Mendelian randomization (MR) identifies a causal relationship between higher MMP12 and lower CHD (Odds Ratio, OR 0.94) and ischemic stroke (OR 0.90) risk, while reverse MR found that genetic propensity to CHD increased MMP12. Taken together, multivariable MR confirms a direct protective effect of higher plasma MMP12 on CHD risk and a genetic effect of atherosclerosis and CHD on elevating MMP12. CONCLUSIONS: Proteomic analyses reveal associations with incident CHD and genomic evidence suggests that therapeutic MMP12 inhibition may confer adverse cardiovascular effects.

Journal Article↗
PubMed2006

Functional variants in the lymphotoxin-alpha gene predict cardiovascular disease in dialysis patients.

TNF-beta that is encoded by lymphotoxin-alpha gene (LTA) regulates adhesion molecules and IL-6. Previously, a genome-wide case-control study showed that LTA gene variants predisposed to cardiovascular disease (CVD). In a prospective study of 775 dialysis patients, LTA and IL-6 gene variants were tested as independent predictors of CVD risk. Four polymorphisms in the LTA gene and one in the IL-6 gene were genotyped. CVD events were ascertained from medical records. During a mean follow-up of 2.6 yr, 294 first-incident CVD events occurred. The LTA 26Asn variant predicted higher adjusted CVD risk (hazard ratio HR 1.33 for each additional copy of Asn allele; 95% confidence interval 1.14 to 1.55; P = 0.0003). Two other nonsynonymous polymorphisms in the LTA, 13Agr and 51Pro, were associated with lower inflammatory activity and CVD risk. LTA haplotypes (based on all four single-nucleotide polymorphisms) were associated with inflammatory markers and predicted CVD risk (P = 0.005) after adjustment. These LTA genotype associations were independent of the IL-6 -174G/C genotype association that was reported recently. LTA and IL-6 gene variants independently predicted risk for CVD among dialysis patients, suggesting that susceptibility in multiple inflammatory pathways contribute to the development of CVD.

Adult↗
PubMed2006

Cardiovascular risk among adults with chronic kidney disease, with or without prior myocardial infarction.

OBJECTIVES: This study sought to determine whether chronic kidney disease (CKD) should be considered a coronary heart disease (CHD) risk equivalent for cholesterol treatment. BACKGROUND: It is unclear whether patients with CKD have a risk of CHD events or cardiovascular disease (CVD) mortality equivalent to patients with a prior myocardial infarction (MI). METHODS: Using data from the ARIC (Atherosclerosis Risk in Communities) study, we categorized nondiabetic participants based on their average level of kidney function (estimated glomerular filtration rate > or =60 or 30 to 59 ml/min/1.73 m2, which defines stage 3 CKD) and on prior MI (yes or no). Rates and relative risks (RR) of CHD (MI or fatal CHD) events (n = 653) and CVD mortality (n = 209) that occurred over 10 years were compared across these populations. RESULTS: Among 12,243 middle-age participants, 271 had stage 3 CKD. After adjustment for age, gender, race, and center, CHD incidence and CVD mortality rates per 1,000 person-years by presence of CKD and MI were 4.1 and 1.0 in the presence of neither condition, 8.0 and 3.4 in CKD only, 18.8 and 7.0 in MI only, and 30.8 and 18.0 in CKD and MI. After further adjustment for CVD risk factors, RR of CHD and CVD mortality were statistically significantly lower in subjects with CKD and no prior MI (RR = 0.44 [95% confidence interval (CI) 0.28 to 0.72] for CHD and RR = 0.46 [95% CI 0.24 to 0.90] for CVD mortality) than for subjects with no CKD and a prior MI. CONCLUSIONS: Stage 3 CKD confers CHD risk that is lower and not equivalent to a prior MI in this middle-aged, general, nondiabetic population.

Cardiovascular Diseases↗
PubMed2006

Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate.

BACKGROUND: Glomerular filtration rate (GFR) estimates facilitate detection of chronic kidney disease but require calibration of the serum creatinine assay to the laboratory that developed the equation. The 4-variable equation from the Modification of Diet in Renal Disease (MDRD) Study has been reexpressed for use with a standardized assay. OBJECTIVE: To describe the performance of the revised 4-variable MDRD Study equation and compare it with the performance of the 6-variable MDRD Study and Cockcroft-Gault equations. DESIGN: Comparison of estimated and measured GFR. SETTING: 15 clinical centers participating in a randomized, controlled trial. PATIENTS: 1628 patients with chronic kidney disease participating in the MDRD Study. MEASUREMENTS: Serum creatinine levels were calibrated to an assay traceable to isotope-dilution mass spectrometry. Glomerular filtration rate was measured as urinary clearance of 125I-iothalamate. RESULTS: Mean measured GFR was 39.8 mL/min per 1.73 m2 (SD, 21.2). Accuracy and precision of the revised 4-variable equation were similar to those of the original 6-variable equation and better than in the Cockcroft-Gault equation, even when the latter was corrected for bias, with 90%, 91%, 60%, and 83% of estimates within 30% of measured GFR, respectively. Differences between measured and estimated GFR were greater for all equations when the estimated GFR was 60 mL/min per 1.73 m2 or greater. LIMITATIONS: The MDRD Study included few patients with a GFR greater than 90 mL/min per 1.73 m2. Equations were not compared in a separate study sample. CONCLUSIONS: The 4-variable MDRD Study equation provides reasonably accurate GFR estimates in patients with chronic kidney disease and a measured GFR of less than 90 mL/min per 1.73 m2. By using the reexpressed MDRD Study equation with the standardized serum creatinine assay, clinical laboratories can report more accurate GFR estimates.

Adult↗
PubMed2006

An assessment of incremental coronary risk prediction using C-reactive protein and other novel risk markers: the atherosclerosis risk in communities study.

BACKGROUND: There has been interest in recent years in whether additional, and in particular novel, risk factors or blood markers, such as C-reactive protein, can enhance existing coronary heart disease (CHD) prediction models. METHODS: Using a series of case-cohort studies, the prospective Atherosclerosis Risk in Communities (ARIC) Study assessed the association of 19 novel risk markers with incident CHD in 15,792 adults followed up since 1987-1989. Novel markers included measures of inflammation, endothelial function, fibrin formation, fibrinolysis, B vitamins, and antibodies to infectious agents. Change in the area under the receiver operating characteristic curve (AUC) was used to assess the additional contribution of novel risk markers to CHD prediction beyond that of traditional risk factors. RESULTS: The basic risk factor model, which included traditional risk factors (age, race, sex, total and high-density lipoprotein cholesterol levels, systolic blood pressure, antihypertensive medication use, smoking status, and diabetes), predicted CHD well, as evidenced by an AUC of approximately 0.8. The C-reactive protein level did not add significantly to the AUC (increase in AUC of 0.003), and neither did most other novel risk factors. Of the 19 markers studied, lipoprotein-associated phospholipase A(2), vitamin B(6), interleukin 6, and soluble thrombomodulin added the most to the AUC (range, 0.006-0.011). CONCLUSIONS: Our findings suggest that routine measurement of these novel markers is not warranted for risk assessment. On the other hand, our findings reinforce the utility of major, modifiable risk factor assessment to identify individuals at risk for CHD for preventive action.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2006

Haplotype of signal transducer and activator of transcription 3 gene predicts cardiovascular disease in dialysis patients.

Signal transducer and activator of transcription 3 (STAT3) protein has been linked to cardiovascular disease (CVD) through multiple pathways in experimental and animal studies. STAT3 gene variation was examined as a predictor of incident CVD in a subcohort of 529 incident white dialysis patients. Fifteen single-nucleotide polymorphisms of the STAT3 gene were genotyped. Haplotypes were estimated using software PHASE 2.1, and associations with first CVD event were tested using Cox proportional hazards analysis. Adjusted global tests of haplotype association with incident CVD and inflammation markers were performed using permutated P value in R-package Haplo.score. An a priori specified additive genetic model was assumed for haplotype analysis. Both genotypes (four single nucleotide polymorphisms with P < 0.001) and haplotypes (P = 0.002 overall) were associated with incident CVD. Two major haplotype blocks, blocks A and C, were identified. Compared with common haplotype A-1, A-3 was associated with a hazard ratio (HR) of 0.70 (95% confidence interval [CI] 0.51 to 0.94) for CVD events after adjustment for covariates including C-reactive protein (CRP) and interleukin 6. Compared with common haplotype C-1, C-3 was associated with an adjusted HR of 2.12 (95% CI 1.25 to 3.57) for CVD events. Associations were independent of inflammation markers, but IL-6 levels were 14% lower (geometric mean ratio 0.86; 95% CI 0.77 to 0.96) per copy of haplotype A-3 compared with haplotype A-1 in block A after adjustment for CRP and other risk factors (P = 0.008). Variation in the STAT3 gene is associated with the risk for CVD among white dialysis patients independent of serum IL-6 and CRP levels.

Aged↗
PubMed2006

International comparison of the relationship of chronic kidney disease prevalence and ESRD risk.

ESRD incidence is much lower in Europe compared with the United States. This study investigated whether this reflects a difference in the prevalence of earlier stages of chronic kidney disease (CKD) or other mechanisms. CKD prevalence in Norway was estimated from the population-based Health Survey of Nord-Trondelag County (HUNT II), which included 65,181 adults in 1995 through 1997 (participation rate 70.4%). Data were analyzed using the same methods as two US National Health and Nutrition Examination Surveys in 1988 through 1994 (n = 15,488) and 1999 through 2000 (n = 4101). The primary analysis used gender-specific cutoffs in estimating persistent albuminuria for CKD stages 1 and 2. ESRD rates and other relevant data were extracted from national registries. Total CKD prevalence in Norway was 10.2% (SE 0.5): CKD stage 1 (GFR >90 ml/min per 1.73 m2 and albuminuria), 2.7% (SE 0.3); stage 2 (GFR 60 to 89 ml/min per 1.73 m2 and albuminuria), 3.2% (SE 0.4); stage 3 (GFR 30 to 59 ml/min per 1.73 m2), 4.2% (SE 0.1); and stage 4 (GFR 15 to 29 ml/min per 1.73 m2), 0.2% (SE 0.01). This closely approximates reported US CKD prevalence (11.0% in 1988 through 1994 and 11.7% in 1999 through 2000). The relative risk for progression from CKD stages 3 or 4 to ESRD in US white patients compared with Norwegian patients was 2.5. This was only modestly modified by adjustment for age, gender, and diabetes. Age and GFR at start of dialysis were similar, hypertension and cardiovascular mortality in the populations were comparable, but US white patients were referred later to a nephrologist and had higher prevalence of obesity and diabetes. In conclusion, CKD prevalence in Norway was similar to that in the United States, suggesting that lower progression to ESRD rather than a smaller pool of individuals at risk accounts for the lower incidence of ESRD in Norway.

Age Distribution↗
PubMed2006

IL-6 haplotypes, inflammation, and risk for cardiovascular disease in a multiethnic dialysis cohort.

It is unknown whether IL-6, a central regulator of inflammation, is a cause of or just a marker of atherosclerosis. Studies of genetic susceptibility to inflammation, however, avoid the potential for reverse causality. Variation in IL6 gene was studied as a predictor of cardiovascular disease (CVD) risk in a cohort of 775 incident dialysis patients, in whom IL-6 levels are elevated. On the basis of published resequencing data on the IL6 gene, a phylogenetic tree with three main branches (clades 1 to 3) was constructed. Two "clade tag" polymorphisms, -174G/C and 1888G/T, and two missense variants, Pro32Ser and Asp162Val, were genotyped. Circulating IL-6 and albumin were measured a median of 5 mo after the start of dialysis. CVD events were ascertained from medical records. During a median follow-up of 2.5 yr, 294 CVD events occurred. The two coding variants, Pro32Ser (present only in black patients, 10% Ser allele) and Asp162Val (present only in white patients, 1% Val), were associated with lower levels of IL-6 and higher levels of albumin. The common variant in the promoter region, -174G/C, was strongly associated with higher CVD risk and weakly with IL-6 levels. Clade 3 (-174C carriers in the absence of 162 Val allele) was associated with higher IL-6 levels (P=0.03) and higher CVD risk (hazard ratio 1.44, P=0.006) after adjustment for covariates. The IL6 gene has functional variants that affect inflammation and risk for CVD among dialysis patients, supporting a causal role for IL6 in CVD.

Adult↗
PubMed2006

Genetic variation of the renin-angiotensin system and chronic kidney disease progression in black individuals in the atherosclerosis risk in communities study.

The renin-angiotensin system (RAS) regulates BP and may affect chronic kidney disease (CKD) through induction of tissue growth and fibrosis. The angiotensinogen (AGT) promoter G(-6) allele lowers transcription and is inversely associated with hypertension. In white individuals, the A1166C 3'-UTR variant of angiotensin II type 1 receptor (AT1R) has been associated with CKD. CKD associations with these RAS genes are uncertain in high-risk black populations. A prospective population-based study of CKD risk was conducted among 3706 black individuals without severe renal dysfunction at baseline (serum creatinine > or =177 micromol/L [2.0 mg/dl] for men, > or =159 micromol/L [1.8 mg/dl] for women) to examine associations with AGT and AT1R. Incident CKD progression was defined as kidney disease hospitalization or increase in serum creatinine level > or =35 micromol/L (0.4 mg/dl) above baseline. During mean follow-up of 10.2 yr, CKD progression incidence rate (per 1000 person-years) was 8.2 (n = 312 cases). Risk was lower for AGT G(-6) carriers compared with A(-6) (incidence 6.9 versus 9.0; log-rank P = 0.03) and nonsignificantly higher among AT1R C1166 carriers. Adjusting for hypertension and major CKD risk factors, AGT G(-6)decreased risk (relative risk 0.75; 95% confidence interval 0.57 to 0.98). AT1R C1166 increased risk only among those with hypertension (relative risk 1.65; 95% confidence interval 1.14 to 2.39). The AGT G(-6)A polymorphism may play a role in CKD progression in black individuals, consistent with in vitro effects on AGT levels and renal remodeling but independent of BP. The AT1R C1166 allele may increase susceptibility but only in the presence of hypertension.

Black or African American↗
PubMed2006

Kidney function and anemia as risk factors for coronary heart disease and mortality: the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Kidney failure causes anemia and is associated with a very high risk of coronary heart disease (CHD). Mildly to moderately decreased kidney function is far more common and also is associated with an elevated prevalence of anemia and CHD risk. Recent data suggest an even higher risk of CHD when both conditions are present. METHODS: We investigated the association of kidney dysfunction and anemia with CHD events (fatal or nonfatal CHD or coronary revascularization procedures) and CHD and all-cause mortality over 12 years of follow-up in 14971 adults aged 45 to 64 years in the ARIC Study. Glomerular filtration rate (GFR) was estimated from calibrated serum creatinine using the MDRD Study equation (< 30 mL/min per 1.73 m2 excluded, n = 32). Anemia was defined as hemoglobin level < 13.5 g/dL in men (648/6746, 9.6%) and < 12 g/dL in women (1049/8225, 12.8%). RESULTS: The prevalence of anemia was progressively higher at lower estimated GFR < 75 mL/min per 1.73 m2 (both P < .001) for both men and women. A total of 1635 (10.9%) participants had a CHD event, 360 (2.4%) died of CHD, and 1722 (11.5%) died of any cause during follow-up. After adjustment for known risk factors, including diabetes, lipid levels, blood pressure, and use of antihypertensive medication, decreased kidney function was associated with a higher risk of recurrent CHD events and mortality from CHD and all causes. These associations were significantly stronger among participants with anemia. The adjusted relative hazards of all-cause mortality associated with moderately decreased versus normal kidney function (GFR 30-59 vs > or = 90 mL/min per 1.73 m2) were 1.7 (95% CI 1.3-2.2) in the absence of anemia and 3.5 (95% CI 2.4-5.1) in the presence of anemia (P interaction = .001). CONCLUSIONS: The combination of moderately decreased kidney function and anemia is associated with an increased risk of CHD events and mortality, emphasizing the need to identify individuals with these conditions and evaluate interventions to treat anemia and slow the progression of chronic kidney disease.

Anemia↗
PubMed2006

NOS3 polymorphisms, cigarette smoking, and cardiovascular disease risk: the Atherosclerosis Risk in Communities study.

OBJECTIVE: Endothelial nitric oxide synthase (NOS3) activity and cigarette smoking significantly influence endothelial function. We sought to determine whether cigarette smoking modified the association between NOS3 polymorphisms and risk of coronary heart disease or stroke. METHODS: All 1085 incident coronary heart disease cases, all 300 incident ischemic stroke cases, and 1065 reference individuals from the Atherosclerosis Risk in Communities study were genotyped for the T-786C and E298D polymorphisms in NOS3. Using a case-cohort design, associations between genotype/haplotype and disease risk were evaluated by multivariable proportional hazards regression. Multiplicative scale interaction testing evaluated the influence of cigarette smoking history at baseline on these associations. RESULTS: In Caucasians, association between E298D genotype and risk of coronary heart disease was significantly modified by current smoking status (interaction P=0.013), with the highest risk observed in smokers carrying the variant D298 allele relative to nonsmokers carrying two E298 alleles (adjusted hazard rate ratio 2.07, 95% confidence interval 1.39-3.07). In African-Americans, association between T-786C genotype and risk of ischemic stroke was significantly modified by pack-year smoking history (interaction P=0.037), with the highest risk observed in >or=20 pack-year smokers carrying the variant C-786 allele relative to <20 pack-year smokers carrying two T-786 alleles (adjusted hazard rate ratio 4.03, 95% confidence interval 1.54-10.6). CONCLUSIONS: An interaction between the E298D and T-786C polymorphisms in NOS3, cigarette smoking, and risk of incident coronary heart disease and ischemic stroke events appears to exist, suggesting a potential complex interplay between genetic and environmental factors and cardiovascular disease risk.

Black or African American↗
PubMed2006

Kidney function estimating equations: where do we stand?

PURPOSE OF REVIEW: Estimation of the glomerular filtration rate (GFR) is central to the diagnosis, evaluation and management of chronic kidney disease. This review summarizes recent data on the performance of equations using serum creatinine to estimate the GFR, particularly the Modification of Diet in Renal Disease (MDRD) Study equation. RECENT FINDINGS: During 2005 GFR estimation has received substantial attention with a focus on comparing the MDRD Study equation with the Cockcroft-Gault equation. Several large studies (n>500) have appeared. Most studies discuss creatinine calibration but few were able to standardize measurements. Studies that did calibrate the creatinine had improved performance. Overall, the MDRD Study equation performed well in populations with a low range of GFR and often outperformed the Cockcroft-Gault equation. Both equations have lower precision in high GFR populations, and the MDRD equation under-estimated the GFR in a number of studies. Efforts are underway to develop improved prediction equations by pooling data across many study populations. SUMMARY: Equations for estimating the GFR from serum creatinine are useful for systematic staging of chronic kidney disease. The MDRD Study equation and systematic creatinine assay calibration improve the level of precision and accuracy in many settings. GFR estimates are less useful in the normal range of GFR, however, and are sensitive to the population under study.

Calibration↗
PubMed2006

Parity and risk of type 2 diabetes: the Atherosclerosis Risk in Communities Study.

OBJECTIVE: While high parity is hypothesized to be associated with insulin resistance and type 2 diabetes, few studies have examined this association in diverse racial samples or geographical areas. Our objectives were to estimate the magnitude of association between parity and diabetes and to determine if higher parity is predictive of future risk of diabetes. RESEARCH DESIGN AND METHODS: This was a population-based, prospective cohort study of 7,024 Caucasian and African-American women from the Atherosclerosis Risk in Communities study, a prospective epidemiological study of men and women aged 45-64 years, with 9 years of follow-up. Incident diabetes was defined by the 1997 American Diabetes Association diagnostic criteria. Parity was defined as the number of live births (no live births [nulliparity], one to two live births, three to four live births, and five or more live births [grandmultiparity]). Parity and risk of diabetes was estimated for 754 incident cases of diabetes with Cox proportional hazard regression models, adjusting for sociodemographic, clinical, and lifestyle factors and inflammatory markers. RESULTS: Incidence rates were highest among women with five or more live births (23/1,000 person-years [95% CI 20.3-26.7]) and lowest among women with one to two live births (11/1,000 person-years [9.6-12.5]). Adjustment indicated that much of the risk was due to sociodemographic factors and higher obesity, but after adjustment for all covariates, grandmultiparity (five or more) was still associated with a 27% increased risk for diabetes (hazard ratio 1.27 [95% CI 1.02-1.57]). CONCLUSIONS: Grandmultiparity is predictive of future risk of diabetes after adjustment for confounders.

Atherosclerosis↗
PubMed2006

The burden and treatment of diabetes in elderly individuals in the u.s.

OBJECTIVE: To assess the prevalence of diabetes, distinguishing between elderly individuals with diabetes diagnosed in middle age ("middle age-onset diabetes") from elderly individuals with recently diagnosed diabetes ("elderly onset diabetes") and to assess the burden of complications and control of cardiovascular risk factors in these groups. RESEARCH DESIGN AND METHODS: We analyzed data from 2,809 elderly individuals from the 1999-2002 National Health and Nutrition Examination Survey, a cross-sectional nationally representative survey of the civilian noninstitutionalized population of the U.S. RESULTS: Among adults aged >/=65 years, the prevalence of diagnosed diabetes was 15.3%, representing 5.4 million individuals in the U.S. The prevalence of undiagnosed diabetes was 6.9% or 2.4 million individuals. Elderly individuals with middle age-onset diabetes had a much greater burden of microvascular disease but have a similar burden of macrovascular disease compared with individuals with elderly onset diabetes. Elderly individuals with middle age-onset diabetes had substantially worse glycemic control (proportion of individuals with HbA(1c) >7% = 59.9%) compared with either elderly onset (41.6%) or nonelderly individuals with diabetes (55.3%). Individuals with elderly onset diabetes were also less likely to be taking glucose-lowering medications. CONCLUSIONS: In this study, we documented a high prevalence of diabetes among elderly individuals and high rate of poor glycemic control in this population. Individuals with middle age-and elderly onset diabetes appear to represent distinct groups with differing burdens of disease and possibly differing treatment goals. Future studies of diabetes in elderly individuals may need to consider stratification based on age of diagnosis.

Adult↗
PubMed2006

HbA1c and peripheral arterial disease in diabetes: the Atherosclerosis Risk in Communities study.

OBJECTIVE: To assess the relation between HbA(1c) (A1C) and incident peripheral arterial disease (PAD) in a community-based cohort of diabetic adults from the Atherosclerosis Risk in Communities (ARIC) study. A second aim was to investigate whether the association was stronger for severe, symptomatic disease compared with PAD assessed by low ankle-brachial index (ABI). RESEARCH DESIGN AND METHODS: This was a prospective cohort study of 1,894 individuals with diabetes using ARIC visit 2 as baseline (1990-1992) with follow-up for incident PAD through 2002. We assessed the relation between A1C and incident PAD, defined by intermittent claudication, PAD-related hospitalization, or a low ABI (<0.9). RESULTS: During a mean follow-up of 9.8 years, the crude incidence rates were 2.1 per 1,000 person-years for intermittent claudication (n = 41), 2.9 per 1,000 person-years for PAD-related hospitalization (n = 57), and 18.9 per 1,000 person-years for low ABI at visit 3 or 4 (n = 123). The relative risk (RR) (95% CI) of an incident PAD event comparing the second and third tertiles of A1C to the first, respectively, after adjustment for cardiovascular risk factors was strongest for severe, symptomatic forms of disease, e.g., PAD-related hospitalization (RR = 4.56 [1.86-11.18] for the third A1C tertile compared with the first, P trend <0.001) than for low ABI (RR = 1.64 [0.94-2.87], P trend = 0.08). CONCLUSIONS: We found a positive, graded, and independent association between A1C and PAD risk in diabetic adults. This association was stronger for clinical (symptomatic) PAD, whose manifestations may be related to microvascular insufficiency, than for low ABI. Our results suggest that efforts to improve glycemic control in persons with diabetes may substantially reduce the risk of PAD.

Cohort Studies↗