Prediabetes Defined by First Measured HbA1c Predicts Higher Cardiovascular Risk Compared With HbA1c in the Diabetes Range: A Cohort Study of Nationwide Registries

10.2337/figshare.16649185.v1 ◽

2021 ◽

Author(s):

Sam Kafai Yahyavi ◽

Ole Snorgaard ◽

Filip Krag Knop ◽

Morten Schou ◽

Christina Lee ◽

...

Keyword(s):

Cardiovascular Risk ◽

Cox Regression ◽

Absolute Risk ◽

Major Adverse Cardiovascular Events ◽

Diagnostic Threshold ◽

Hazard Ratios ◽

All Cause Mortality ◽

Design And Methods ◽

Hba1c Measurement ◽

First Time

Objective: To assess the risk of major adverse cardiovascular events (MACE), all-cause mortality, and initiation of medical treatment in subjects with prediabetes according to first-time measured HbA1c. Research design and methods: Through registry databases, we identified 326,305 Danish patients with a first HbA1c between 40-51 mmol/mol (5.8-6.8%) from 2011 to 2017. After exclusion of patients with prior disease, 84,678 patients were followed 12 months after first HbA1c measurement. Cox regression models were used to estimate hazard ratios (HRs) of MACE and standardized absolute risks. Cumulative incidences were used to analyse initiation of glucose-lowering, anti-hypertensive, cholesterol-lowering and anti-thrombotic medication. Results: The 12-months risk of MACE and all-cause mortality increased gradually with increasing HbA1c until 47 mmol/mol (6.5%). Compared to HbA1c of 40-41 mmol/mol (5.8-5.9%), subjects with HbA1c of 46-47 mmol/mol (6.4-6.5%) had a 0.79% (95% CI 0.33-1.24) higher standardized absolute risk and a HR of 2.21 (95% CI 1.67-2.92) of MACE. Patients with a HbA1c of 48-49 mmol/mol (6.5-6.6%) had a -0.09% (95% CI -0.35-0.52) lower absolute risk and a HR of 1.33 (95% CI 0.87-2.05) of MACE. Initiation of medication was significantly lower among patients with HbA1c of 46-47 mmol/mol (6.4-6.5%) compared to patients with HbA1c of 48-49 mmol/mol (6.5-6.6%). Conclusion: In the D<a>anish population screened for diabetes with HbA1c, the highest risk of MACE and all-cause mortality was found in subjects with HbA1c just below the diagnostic threshold for diabetes. Our results highlight the need for increased focus on the treatment of cardiovascular risk-factors in subjects with prediabetes.</a>

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Changes in Albuminuria Predict Cardiovascular and Renal Outcomes in Type 2 Diabetes: A Post Hoc Analysis of the LEADER Trial

10.2337/figshare.13528037.v1 ◽

2021 ◽

Author(s):

Frederik Persson ◽

Stephen C Bain ◽

Ofri Mosenzon ◽

Hiddo J.L. Heerspink ◽

Johannes F. E. Mann ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cox Regression ◽

Major Adverse Cardiovascular Events ◽

First Year ◽

Treatment Groups ◽

Renal Outcomes ◽

Hazard Ratios ◽

Post Hoc ◽

Design And Methods

OBJECTIVE A post hoc analysis to investigate the association between 1-year changes in albuminuria and subsequent risk of cardiovascular and renal events. RESEARCH DESIGN AND METHODS LEADER was a randomized trial of liraglutide up to 1.8 mg/day versus placebo added to standard care for 3.5–5 years, in 9,340 participants with type 2 diabetes and high cardiovascular risk. We calculated change in urinary albumin-to-creatinine ratio (UACR) from baseline to 1 year in participants with >30% reduction (N=2,928), 30–0% reduction N=1,218) or any increase in UACR (N=4,124) irrespective of treatment. Using Cox regression, risks of major adverse cardiovascular events (MACE) and a composite nephropathy outcome (from 1 year to end of trial in subgroups by baseline UACR [<30 mg/g, 30–300 mg/g or ≥300 mg/g]) were assessed. The analysis was adjusted for treatment allocation alone as a fixed factor and for baseline variables associated with cardiovascular and renal outcomes. RESULTS For MACE, hazard ratios (HRs) for those with >30% and 30%–0% UACR reduction were 0.82 (95% CI 0.71–0.94; P=0.006) and 0.99 (0.82–1.19; P=0.912), respectively, compared with any increase in UACR (reference). For the composite nephropathy outcome, respective HRs (95% CI) were 0.67 (0.49–0.93; P=0.02) and 0.97 (0.66–1.43; P=0.881). Results were independent of baseline UACR and consistent in both treatment groups. After adjustment, HRs were significant and consistent in >30% reduction subgroups with baseline micro- or macroalbuminuria. CONCLUSIONS A reduction in albuminuria during the first year was associated with fewer cardiovascular and renal outcomes, independent of treatment. Albuminuria monitoring remains an important part of diabetes care, with great unused potential.

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Changes in Albuminuria Predict Cardiovascular and Renal Outcomes in Type 2 Diabetes: A Post Hoc Analysis of the LEADER Trial

10.2337/figshare.13528037 ◽

2021 ◽

Author(s):

Frederik Persson ◽

Stephen C Bain ◽

Ofri Mosenzon ◽

Hiddo J.L. Heerspink ◽

Johannes F. E. Mann ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cox Regression ◽

Major Adverse Cardiovascular Events ◽

First Year ◽

Treatment Groups ◽

Renal Outcomes ◽

Hazard Ratios ◽

Post Hoc ◽

Design And Methods

OBJECTIVE A post hoc analysis to investigate the association between 1-year changes in albuminuria and subsequent risk of cardiovascular and renal events. RESEARCH DESIGN AND METHODS LEADER was a randomized trial of liraglutide up to 1.8 mg/day versus placebo added to standard care for 3.5–5 years, in 9,340 participants with type 2 diabetes and high cardiovascular risk. We calculated change in urinary albumin-to-creatinine ratio (UACR) from baseline to 1 year in participants with >30% reduction (N=2,928), 30–0% reduction N=1,218) or any increase in UACR (N=4,124) irrespective of treatment. Using Cox regression, risks of major adverse cardiovascular events (MACE) and a composite nephropathy outcome (from 1 year to end of trial in subgroups by baseline UACR [<30 mg/g, 30–300 mg/g or ≥300 mg/g]) were assessed. The analysis was adjusted for treatment allocation alone as a fixed factor and for baseline variables associated with cardiovascular and renal outcomes. RESULTS For MACE, hazard ratios (HRs) for those with >30% and 30%–0% UACR reduction were 0.82 (95% CI 0.71–0.94; P=0.006) and 0.99 (0.82–1.19; P=0.912), respectively, compared with any increase in UACR (reference). For the composite nephropathy outcome, respective HRs (95% CI) were 0.67 (0.49–0.93; P=0.02) and 0.97 (0.66–1.43; P=0.881). Results were independent of baseline UACR and consistent in both treatment groups. After adjustment, HRs were significant and consistent in >30% reduction subgroups with baseline micro- or macroalbuminuria. CONCLUSIONS A reduction in albuminuria during the first year was associated with fewer cardiovascular and renal outcomes, independent of treatment. Albuminuria monitoring remains an important part of diabetes care, with great unused potential.

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β-Lactam and Fluoroquinolone Combination Antibiotic Therapy for Bacteremia Caused by Gram-Negative Bacilli

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01231-08 ◽

2009 ◽

Vol 53 (4) ◽

pp. 1386-1394 ◽

Cited By ~ 49

Author(s):

Majdi N. Al-Hasan ◽

John W. Wilson ◽

Brian D. Lahr ◽

Kristine M. Thomsen ◽

Jeanette E. Eckel-Passow ◽

...

Keyword(s):

Combination Therapy ◽

Antibiotic Therapy ◽

Cox Regression ◽

Receive Combination Therapy ◽

Beta Lactam ◽

Beta Lactams ◽

Gram Negative ◽

Hazard Ratios ◽

All Cause Mortality ◽

First Time

ABSTRACT The role of combination antibiotic therapy with a beta-lactam and a fluoroquinolone for bacteremia caused by gram-negative bacilli, to our knowledge, has not been previously described. Much of the previous study of combination therapy has included beta-lactams and aminoglycosides. We conducted a large retrospective cohort study to evaluate 28-day all-cause mortality in patients with monomicrobial bacteremia due to aerobic gram-negative bacilli who received either a combination of beta-lactams and fluoroquinolones or beta-lactam monotherapy. We enrolled adult patients admitted to Mayo Clinic hospitals from 1 January 2001 to 31 October 2006 in the study. After stratification of patients by Pitt bacteremia scores, we used Cox regression models to estimate the hazard ratios (HR) for 28-day all-cause mortality after adjusting for the propensity to receive combination therapy. We identified 398 and 304 unique patients with bacteremia caused by gram-negative bacilli who received single and combination antibiotic therapy, respectively. In less severely ill patients with Pitt bacteremia scores of <4, combination therapy was associated with lower 28-day mortality than single therapy (4.2% [9 of 214] versus 8.8% [28 of 319]; adjusted HR, 0.44; 95% confidence interval [CI], 0.20 to 0.98; P = 0.044). In critically ill patients with Pitt bacteremia scores of ≥4, there was no difference in 28-day mortality between combination and single therapy (25.6% [23 of 90] versus 27.8% [22 of 79]; adjusted HR, 0.87; 95% CI, 0.47 to 1.62; P = 0.660). These findings were consistent for 14-day all-cause mortality. In this large cohort, we found for the first time that combination therapy with beta-lactams and fluoroquinolones was associated with a reduction in 28-day all-cause mortality among less severely ill patients with bacteremia caused by gram-negative bacilli.

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Association between selenium intake, diabetes, and mortality in adults: findings from National Health and Nutrition Examination Survey (NHANES) 2003-2014

British Journal Of Nutrition ◽

10.1017/s000711452100177x ◽

2021 ◽

pp. 1-24

Author(s):

Bushra Hoque ◽

Zumin Shi

Keyword(s):

National Health ◽

Cox Regression ◽

Inverse Association ◽

Nutrition Examination Survey ◽

Health And Nutrition ◽

Hazard Ratios ◽

The Us ◽

All Cause Mortality ◽

Cvd Mortality

Abstract Selenium (Se) is a trace mineral that has antioxidant and anti-inflammatory properties. This study aimed to investigate the association between Se intake, diabetes, all-cause and cause-specific mortality in a representative sample of US adults. Data from 18,932 adults who attended the 2003-2014 National Health and Nutrition Examination Survey (NHANES) were analysed. Information on mortality was obtained from the US mortality registry updated to 2015. Multivariable logistic regression and Cox regression were used. Cross-sectionally, Se intake was positively associated with diabetes. Comparing extreme quartiles of Se intake, the odds ratio (OR) for diabetes was 1.44 (95% CI: 1.09–1.89). During a mean of 6.6 years follow-up, there were 1627 death (312 CVD, 386 cancer). High intake of Se was associated with a lower risk of all-cause mortality. When comparing the highest with the lowest quartiles of Se intake, the hazard ratios (HRs) for all-cause, CVD mortality, cancer mortality and other mortality were: 0.77 (95% CI 0.59-1.01), 0.62 (95% CI, 0.35-1.13), 1.42 (95% CI, 0.78-2.58) and 0.60 (95% CI,0.40-0.80), respectively. The inverse association between Se intake and all-cause mortality was only found among white participants. In conclusion, Se intake was positively associated with diabetes but inversely associated with all-cause mortality. There was no interaction between Se intake and diabetes in relation to all-cause mortality.

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Plasma Vitamin B12 Levels, High-Dose Vitamin B12 Treatment, and Risk of Dementia

Journal of Alzheimer s Disease ◽

10.3233/jad-201096 ◽

2021 ◽

Vol 79 (4) ◽

pp. 1601-1612

Author(s):

Johan Frederik Håkonsen Arendt ◽

Erzsébet Horváth-Puhó ◽

Henrik Toft Sørensen ◽

Ebba Nexø ◽

Lars Pedersen ◽

...

Keyword(s):

Vitamin B12 ◽

Vascular Dementia ◽

Cox Regression ◽

Population Based ◽

High Dose ◽

Plasma Vitamin ◽

Hazard Ratios ◽

B12 Deficiency ◽

First Time

Background: It is controversial whether B12 deficiency causes dementia or B12 treatment can prevent dementia. Objective: To assess associations between low plasma (P-)B12 levels, B12 treatment, and risk of Alzheimer’s disease (AD; primary outcome) and all-cause or vascular dementia (secondary outcomes). Methods: We conducted a population-based cohort study using Danish registry data to assess associations between low P-B12 levels, high-dose injection or oral B12 treatment, and risk of dementia (study period 2000–2013). The primary P-B12 cohort included patients with a first-time P-B12 measurement whose subsequent B12 treatment was recorded. The secondary B12 treatment cohort included patients with a first-time B12 prescription and P-B12 measurement within one year before this prescription. For both cohorts, patients with low P-B12 levels (<200 pmol/L) were propensity score-matched 1:1 with patients with normal levels (200–600 pmol/L). We used multivariable Cox regression to compute 0–15-year hazard ratios for dementia. Results: For low P-B12 and normal P-B12 level groups, we included 53,089 patients in the primary P-B12 cohort and 13,656 patients in the secondary B12 treatment cohort. In the P-B12 cohort, hazard ratios for AD centered around one, regardless of follow-up period or treatment during follow-up. In the B12 treatment cohort, risk of AD was unaffected by low pre-treatment P-B12 levels, follow-up period and type of B12 treatment. Findings were similar for all-cause and vascular dementia. Conclusion: We found no associatio1n between low P-B12 levels and dementia. Associations were unaffected by B12 treatment. Results do not support routine screening for B12 deficiency in patients with suspected dementia.

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Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio as a risk factor for mortality in peruvian adults with chronic kidney disease.

10.22541/au.161224727.78237032/v1 ◽

2021 ◽

Author(s):

Gianfranco Umeres-Francia1 ◽

María Rojas-Fernández ◽

Percy Herrera Añazco ◽

Vicente Benites-Zapata

Keyword(s):

Risk Factor ◽

Cox Regression ◽

Outcome Variable ◽

Lymphocyte Ratio ◽

Hazard Ratios ◽

Ckd Stage ◽

All Cause Mortality ◽

The Relationship ◽

Crude Analysis

Objective: To assess the association between NLR and PLR with all-cause mortality in Peruvian patients with CKD Methods: We conducted a retrospective cohort study in adults with CKD in stages 1 to 5. The outcome variable was mortality and as variables of exposure to NLR and PLR. Both ratios were categorized as high with a cut-off point of 3.5 and 232.5; respectively. We carried out a Cox regression model and calculated crude and adjusted hazard ratios (HR) with their 95% confidence interval (95%CI). Results: We analyzed 343 participants with a median follow-up time of 2.45 years (2.08-3.08). The frequency of deaths was 17.5% (n=60). In the crude analysis, the high NLR and PLR were significantly associated with all-cause mortality (HR=2.01; 95% CI:1.11-3.66) and (HR=2.58; 95% CI:1.31-5.20). In the multivariate model, after adjusting for age, sex, serum creatinine, CKD stage, albumin and hemoglobin, the high NLR and PLR remained as an independent risk factor for all-cause mortality, (HR=2.10; 95% CI:1.11-3.95) and (HR=2.71; 95% CI:1.28-5.72). Conclusion: Our study suggests the relationship between high NLR and PLR with all-cause mortality in patients with CKD.

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Abstract TP431: Association of Systolic Blood Pressure and Cardiovascularrisk According to Hemoglobin Concentration

Stroke ◽

10.1161/str.51.suppl_1.tp431 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Jun Young Chang ◽

Se Young Jang ◽

Sun-uck Kwon

Keyword(s):

Blood Pressure ◽

Cardiovascular Risk ◽

Systolic Blood Pressure ◽

Cox Regression ◽

Hemoglobin Concentration ◽

Cardiovascular Death ◽

Normal Range ◽

Cox Regression Analysis ◽

Hazard Ratios ◽

Hb Concentration

Introduction: We evaluated whether the optimal cutoff of blood pressure to reduce cardiovascular risk is different according to hemoglobin (Hb) concentration and its changing pattern using the National Health Insurance Service-Health Screening Cohort. Methods: The study population consisted of individuals who underwent both 2002-2003 and 2004-2005 health examinations. Individuals who were diagnosed with cardiovascular disease or who died before index date of 1 January 2006 were excluded. The primary outcome of the study was the association between systolic blood pressure (SBP) and MACE (composite of myocardial infarction, stroke, and cardiovascular death) according to Hb concentration. Hazard ratios (HR) were calculated using Cox regression analysis adjusted for age and sex. Results: A total of 290573 were included in the analysis. During the follow up period from 1 January 2006 to 31 December 2013, a total of 18292 experienced MACE. There was a significant interaction between SBP and Hb concentration with regard to cardiovascular diseases (p for interaction= 0.07). Among the subjects with Hb <10, a significant increment of MACE was observed when SBP ≥140 mmHg. HR for MACE increased when SBP ≥130mmHg among the subjects with 10≤ Hb <11 and 11≤ Hb <12. HR for MACE increased when SBP ≥ 120 mmHg among the subjects with 12≤ Hb <13, 13≤ Hb <15, and 15≤ Hb. Cardiovascular risk was the lowest in SBP below 120mmHg and cut off value for increasing cardiovascular risk was 120 mmHg or above in subjects who maintain normal range of hemoglobin level and whose hemoglobin concentration changed from anemia to normal range. However, individuals who maintain anemic state and whose hemoglobin concentration changed from normal range to anemia, SBP threshold for increasing cardiovascular risk was equal or above 130 mmHg . Conclusion: The threshold of SBP which increases cardiovascular risk may be different according to the hemoglobin concentration and change pattern of hemoglobin.

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P4792Dabigatran versus vitamin K antagonists in patients with atrial fibrillation and valvular heart disease

European Heart Journal ◽

10.1093/eurheartj/ehz745.1168 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

J E Strange ◽

C Sindet-Pedersen ◽

L Staerk ◽

E L Grove ◽

T A Gerds ◽

...

Keyword(s):

Atrial Fibrillation ◽

Heart Disease ◽

Vitamin K ◽

Valvular Heart Disease ◽

Cox Regression ◽

Absolute Risk ◽

Risk Difference ◽

Increased Risk ◽

Significant Difference ◽

All Cause Mortality

Abstract Background Atrial fibrillation (AF) and valvular heart disease (VHD) are both associated with an increased risk of stroke. Outside post-hoc analyses of randomized controlled trials, knowledge on the effectiveness and safety of dabigatran in patients with AF and VHD is scarce. Objectives To compare the risk of all-cause mortality, stroke, and bleeding in patients with AF and VHD treated with dabigatran or a vitamin K antagonist (VKA). Methods All Danish residents are provided a unique personal identification number enabling cross-linking of data from Danish nationwide registries. We identified all patients with AF and VHD initiating treatment with dabigatran or VKA between the 22nd of August 2011 and the 31st of December 2014. We defined VHD as aortic stenosis/regurgitation, mitral regurgitation, bioprosthetic heart valves, mitral-, and aortic valve repair. Outcomes were all-cause mortality, stroke, and bleeding. 2-year standardized absolute risks were calculated from cause-specific Cox regression models with death as competing risk. Results In total, 599 (27.3%) and 1,596 (72.7%) patients initiated treatment with dabigatran and VKA. The 2-year standardized absolute risk of all-cause mortality (95% CI) for VKA was 27.6% (25.1% to 30.1%) and 25.4% (21.8% to 29.0%) for dabigatran with a corresponding absolute risk difference of −2.2% (−6.3% to 1.9%) (Figure 1). The 2-year standardized absolute risk of stroke for VKA was 3.4% (2.3% to 4.5%) and 3.9% (2.2% to 5.5%) for dabigatran with a corresponding absolute risk difference of 0.5% (−1.6% to 2.5%). Lastly, the 2-year standardized absolute risk of bleeding for VKA was 8.2% (6.6% to 9.7%) and 7.6% (5.1% to 10.1%) for dabigatran with a corresponding absolute risk difference of −0.5% (−3.4% to 2.4%). Figure 1 Conclusions In this nationwide cohort study, we found no significant difference in the risk of all-cause mortality, stroke, or bleeding in patients with AF and VHD when comparing VKA to dabigatran.

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Plasma Trimethylamine N-Oxide and Risk of Cardiovascular Events in Patients With Type 2 Diabetes

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa188 ◽

2020 ◽

Vol 105 (7) ◽

pp. 2371-2380 ◽

Cited By ~ 1

Author(s):

Mikael Croyal ◽

Pierre-Jean Saulnier ◽

Audrey Aguesse ◽

Elise Gand ◽

Stéphanie Ragot ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Events ◽

Tumor Necrosis Factor Receptor ◽

Density Lipoprotein ◽

Major Adverse Cardiovascular Events ◽

Cox Models ◽

Increased Risk ◽

All Cause Mortality ◽

Design And Methods

Abstract Objective Even though trimethylamine N-oxide (TMAO) has been demonstrated to interfere with atherosclerosis and diabetes pathophysiology, the association between TMAO and major adverse cardiovascular events (MACE) has not been specifically established in type 2 diabetes (T2D). Research Design and Methods We examined the association of plasma TMAO concentrations with MACE and all-cause mortality in a single-center prospective cohort of consecutively recruited patients with T2D. Results The study population consisted in 1463 SURDIENE participants (58% men), aged 65 ± 10 years. TMAO concentrations were significantly associated with diabetes duration, renal function, high-density lipoprotein cholesterol, soluble tumor necrosis factor receptor 1 (sTNFR1) concentrations (R2 = 0.27) and were significantly higher in patients on metformin, even after adjustment for estimated glomerular filtration rate (eGFR): 6.7 (8.5) vs 8.5 (13.6) µmol/L, respectively (PeGFR-adjusted = 0.0207). During follow-up (median duration [interquartile range], 85 [75] months), 403 MACE and 538 deaths were registered. MACE-free survival and all-cause mortality were significantly associated with the quartile distribution of TMAO concentrations, patients with the highest TMAO levels displaying the greatest risk of outcomes (P < 0.0001). In multivariate Cox models, compared with patients from the first 3 quartiles, those from the fourth quartile of TMAO concentration had an independently increased risk for MACE: adjusted hazard ratio (adjHR) 1.32 (1.02-1.70); P = 0.0325. Similarly, TMAO was significantly associated with mortality in multivariate analysis: adjHR 1.75 (1.17-2.09); P = 0.0124, but not when sTNFR1 and angiopoietin like 2 were considered: adjHR 1.16 (0.95-1.42); P = 0.1514. Conclusions We revealed an association between higher TMAO concentrations and increased risk of MACE and all-cause mortality, thereby opening some avenues on the role of dysbiosis in cardiovascular risk, in T2D patients.

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