Associations between usual glycated haemoglobin A1c and Cardiovascular Disease in Patients with Type 2 Diabetes Mellitus: A 10‐year Diabetes cohort study

Aims: The long‐term effect of glycated haemoglobin A1c(HbA1c) level on cardiovascular disease(CVD) risks among patients with type 2 diabetes remains controversial. The aim of this study was to investigate their associations. / Materials and methods: This retrospective cohort study conducted in Hong Kong selected patients aged 45‐84 years old with type 2 diabetes mellitus and without CVD in primary care clinics within 2008‐2010. The usual HbA1c measurement was calculated using a mixed effects model to minimize regression dilution bias. The association between usual HbA1c and CVD risk was assessed by Cox regression with adjustment of baseline covariates. Subgroup analyses by patient characteristics were also conducted. / Results: After a median follow‐up period of 8.4years (1.4 million person‐years), 174,028 patients with 34,074 CVD events were observed. Curvilinear association was found between the usual HbA1c and total CVD, stroke, heart failure and CVD mortality risk. No significant difference was found among patients with usual HbA1c7%(53mmol/mol) was 21% (HR: 1.21; 95%C.I. (Confidence Interval): 1.18‐1.23). Similar pattern was identified in patient's subgroups analysis, but the effect of usual HbA1c in younger patients were more prominent than the others. / Conclusions: Increment in usual HbA1c level >7.0% (53mmol/mol) was associated with elevated CVD risk, but no difference was found in population with usual HbA1c<7.0% (53mmol/mol) irrespective of the patients' characteristics. For the CVD prevention, a strict adherence of HbA1c <7% (53 mmol/mol) should apply to patients with younger age

Age-specific associations between Systolic Blood Pressure and Cardiovascular Disease: A 10-years diabetes cohort study

Abstract: Background The relationship between systolic blood pressure (SBP) and cardiovascular disease (CVD) among patients with diabetes mellitus remains unclear. The study aimed to explore age‐specific associations between SBP and CVD. Methods and Results: A population‐based retrospective cohort study was conducted on 180 492 Chinese adults with type 2 diabetes mellitus in 2008–2010, with follow‐up to 2017. Age‐specific associations (<50, 50–59, 60–69, and 70–79 years) between the average SBP in the previous 2 years and CVD risk were assessed by adjusted Cox proportional hazards regression with age‐specific regression dilution ratios and patient characteristics stratified by subgroups. During a median follow‐up of 9.3 years (1.5 million person‐years), 32 545 patients developed a CVD, with an incidence rate of 23.4 per 1000 person‐years. A positive and log‐linear association between SBP and CVD risk was observed among the 4 age groups without evidence of a threshold down to 120 mm Hg, but the magnitude of SBP effect on CVD attenuated with increased age. The CVD risk in the age group <50 years was ≈22% higher than the age group 70 to 79 years (hazard ratio [HR], 1.33 [95% CI, 1.26–1.41] versus HR, 1.09 [95% CI, 1.07–1.11]). Each 10‐mm Hg higher SBP was associated with 12% (HR, 1.12 [95% CI, 1.10–1.13]), 11% (HR, 1.11 [95% CI, 1.10–1.13]), and 20% (HR, 1.20 [95% CI, 1.17–1.22]) higher risk of all composite CVD events, individual CVD, and CVD mortality, respectively. Conclusions: There is a significant log‐linear relationship between baseline SBP and the risk of CVD among patients with diabetes mellitus in China. The risk increases from an SBP of 120 mm Hg onward. Age influences this relationship significantly, with younger patients (<50 years) having a greater risk of CVD for a similar rise in SBP as compared with those who are older. These findings suggest that differential target blood pressures stratified by age maybe usefu

Evaluation of the quality of care of a multi-disciplinary Risk Factor Assessment and Management Programme for Hypertension (RAMP-HT)

Background: There is some evidence to support a risk-stratified, multi-disciplinary approach to manage patients with hypertension in primary care. The aim of this study is to evaluate the quality of care (QOC) of a multi-disciplinary Risk Assessment and Management Programme for Hypertension (RAMP-HT) for hypertensive patients in busy government-funded primary care clinics in Hong Kong. The objectives are to develop an evidence-based, structured and comprehensive evaluation framework on quality of care, to enhance the QOC of the RAMP-HT through an audit spiral of two evaluation cycles and to determine the effectiveness of the programme in reducing cardiovascular disease (CVD) risk. Method/Design: A longitudinal study is conducted using the Action Learning and Audit Spiral methodologies to measure whether pre-set target standards of care intended by the RAMP-HT are achieved. A structured evaluation framework on the quality of structure, process and outcomes of care has been developed based on the programme objectives and literature review in collaboration with the programme workgroup and health service providers. Each participating clinic is invited to complete a structure of care evaluation questionnaire in each evaluation cycle. The data of all patients who have enrolled into the RAMP-HT in the pre-defined evaluation periods are used for the evaluation of the process and outcomes of care in each evaluation cycle. For evaluation of the effectiveness of RAMP-HT, the primary outcomes including blood pressure (both systolic and diastolic), low-density lipoprotein cholesterol and estimated 10-year CVD risk of RAMP-HT participants are compared to those of hypertensive patients in usual care without RAMP-HT. Discussion: The QOC and effectiveness of the RAMP-HT in improving clinical and patient-reported outcomes for patients with hypertension in normal primary care will be determined. Possible areas for quality enhancement and standards of good practice will be established to inform service planning and policy decision making.published_or_final_versio

Comparative Risks of Nonsteroidal Anti-Inflammatory Drugs on CKD

BACKGROUND AND OBJECTIVES: There have been doubts about the association between nonsteroidal anti-inflammatory drug use and worsening kidney function, and whether there is a difference between risks of individual nonsteroidal anti-inflammatory drugs is presently unclear. Therefore, this study aimed to evaluate the association between nonsteroidal anti-inflammatory drug exposure and the risk of incident eGFR <60 ml/min per 1.73 m2 and compare the risks between nonsteroidal anti-inflammatory drug subtypes in the Chinese population. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: From 2008 to 2017, a total of 1,982,488 subjects aged 18 years or older with baseline eGFR ≥60 ml/min per 1.73 m2 were enrolled in this retrospective cohort study. Multivariable Cox proportional hazards regression adjusted for each patient's baseline characteristics was adopted to examine the association between nonsteroidal anti-inflammatory drug and incident eGFR <60 ml/min per 1.73 m2 or eGFR decline ≥30% with reference to baseline. RESULTS: After a median follow-up duration of 6.3 (interquartile range, 3.3-9.4) years, 271,848 cases (14%) of incident eGFR <60 ml/min per 1.73 m2 and 388,386 (21%) events of eGFR decline ≥30% were recorded. After adjusting for each patient's baseline characteristics, nonsteroidal anti-inflammatory drug treatment was shown to be associated with a significantly higher risk of incident eGFR <60 ml/min per 1.73 m2 (hazard ratio, 1.71; 95% confidence interval, 1.67 to 1.75) and eGFR decline ≥30% (hazard ratio, 1.93; 95% confidence interval, 1.89 to 1.96) when compared with no nonsteroidal anti-inflammatory drug, with etoricoxib exhibiting the highest risk of eGFR<60 ml/min per 1.73 m2 (hazard ratio, 3.12; 95% confidence interval, 2.69 to 3.62) and eGFR decline ≥30% (hazard ratio, 3.11; 95% confidence interval, 2.78 to 3.48) and ibuprofen displaying the lowest risk of eGFR<60 ml/min per 1.73 m2 (hazard ratio, 1.12; 95% confidence interval, 1.02 to 1.23) and eGFR decline ≥30% (hazard ratio, 1.32; 95% confidence interval, 1.23 to 1.41). CONCLUSIONS: Nonsteroidal anti-inflammatory drug exposure was associated with higher risks of incident eGFR <60 ml/min per 1.73 m2 and eGFR decline ≥30%. Highest risk was observed in etoricoxib users, and lowest risk was with ibuprofen. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_04_28_CJN18501120.mp3

Diabetes with poor-control HbA1c is cardiovascular disease 'risk equivalent' for mortality: UK Biobank and Hong Kong population-based cohort study

INTRODUCTION: Type 2 diabetes mellitus (T2DM) has traditionally been considered a coronary heart disease 'risk equivalent' for future mortality, but significant heterogeneity exists across people with T2DM. This study aims to determine the risk of all-cause mortality of patients with cardiovascular disease (CVD) and T2DM in UK and Hong Kong, with stratifications for hemoglobin A1 (HbA1c) concentrations, compared with those without CVD and diabetes mellitus. RESEARCH DESIGN AND METHODS: This is a retrospective cohort study of 3 839 391 adults from Hong Kong and a prospective cohort study of 497 779 adults from the UK Biobank. Individuals were divided into seven disease groups: (1) no T2DM and CVD, (2) T2DM only with HbA1c <7%, (3) T2DM only with HbA1c 7%-7.9%, (4) T2DM only with HbA1c 8%-8.9%, (5) T2DM only with HbA1c ≥9%, (6) CVD only, and (7) T2DM and CVD. Differences in all-cause mortality between groups were examined using Cox regression. RESULTS: After around 10 years of median follow-up, 423 818 and 19 844 deaths were identified in the Hong Kong cohort and UK Biobank, respectively. Compared with individuals without T2DM and CVD, the adjusted HR for all-cause mortality in the other six disease groups for the Hong Kong cohort was 1.25 (95% CI 1.23 to 1.27) for T2DM only with HbA1c <7%, 1.21 (95% CI 1.19 to 1.23) for T2DM only with HbA1c 7%-7.9%, 1.36 (95% CI 1.33 to 1.39) for T2DM only with HbA1c 8%-8.9%, 1.82 (95% CI 1.78 to 1.85) for T2DM only with HbA1c ≥9%, 1.37 (95% CI 1.36 to 1.38) for CVD only, and 1.83 (95% CI 1.81 to 1.85) for T2DM and CVD, and for the UK Biobank the HR was 1.45 (95% CI 1.33 to 1.58), 1.50 (95% CI 1.32 to 1.70), 1.72 (95% CI 1.43 to 2.08), 2.51 (95% CI 2.05 to 3.08), 1.67 (95% CI 1.59 to 1.75) and 2.62 (95% CI 2.42 to 2.83), respectively. This indicates that patients with T2DM had an increased risk of mortality compared with those without T2DM and CVD, and in those with HbA1c ≥9% an even higher risk than people with CVD. CONCLUSIONS: Patients with T2DM with poor HbA1c control (8%-8.9% and ≥9%) were associated with similar and higher risk of mortality compared with patients with CVD, respectively. Optimal HbA1c, controlled for risk reduction and prevention of mortality and complications in diabetes management, remains important

Simple non-laboratory-based and laboratory-based risk assessment algorithms and nomogram for detecting undiagnosed diabetes mellitus

This journal suppl. entitled: Abstracts of the 10th International Diabetes Federation–Western Pacific Region Congress and the 6th AASD Scientific MeetingBACKGROUND: Early detection for undiagnosed diabetes mellitus (DM), through routine screening periodically, is critical to prevent or delay severe diabetes-related complications. In order to classify high-risk subjects for DM screening, risk algorithms for undiagnosed DM detection have been richly developed and validated in diverse populations and health care settings. However, the majority of risk algorithms developed within Chinese population were developed and validated in low income setting. Furthermore, there are no nomograms for the use in detecting undiagnosed DM, of which are simple-to-use graphical tool to guide decision-making in both routine clinical practice and community setting. The purpose of this study was to develop simple a nomogram to predict the risk of undiagnosed DM for use in asymptomatic general population, based on non-laboratory-based ...postprin

Age-Specific Associations of Usual Blood Pressure Variability With Cardiovascular Disease and Mortality: 10-Year Diabetes Mellitus Cohort Study

BACKGROUND: The detrimental effects of increased variability in systolic blood pressure (SBP) on cardiovascular disease (CVD) and mortality risk in patients with diabetes mellitus remains unclear. This study evaluated age‐specific association of usual SBP visit‐to‐visit variability with CVD and mortality in patients with type 2 diabetes mellitus. METHODS AND RESULTS: A retrospective cohort study investigated 155 982 patients with diabetes mellitus aged 45 to 84 years without CVD at baseline (2008–2010). Usual SBP variability was estimated using SBP SD obtained from a mixed‐effects model. Age‐specific associations (45–54, 55–64, 65–74, 75–84 years) between usual SBP variability, CVD, and mortality risk were assessed by Cox regression adjusted for patient characteristics. After a median follow‐up of 9.7 years, 49 816 events (including 34 039 CVD events and 29 211 mortalities) were identified. Elevated SBP variability was independently, positively, and log‐linearly associated with higher CVD and mortality risk among all age groups, with no evidence of any threshold effects. The excess CVD and mortality risk per 5 mm Hg increase in SBP variability within the 45 to 54 age group is >3 times higher than the 70 to 79 age group (hazard ratio, 1.66; 95% CI, 1.49–1.85 versus hazard ratio, 1.19; 95% CI, 1.15–1.23). The significant associations remained consistent among all subgroups. Patients with younger age had a higher association of SBP variability with event outcomes. CONCLUSIONS: The findings suggest that SBP visit‐to‐visit variability was strongly associated with CVD and mortality with no evidence of a threshold effect in a population with diabetes mellitus. As well as controlling overall blood pressure levels, SBP visit‐to‐visit variability should be monitored and evaluated in routine practice, in particular for younger patients

The impact of cardiovascular disease and chronic kidney disease on life expectancy and direct medical cost in a 10-year diabetes cohort study

Objective: The relative effects of various cardiovascular diseases (CVD) and varying severity of chronic kidney disease (CKD) on mortality risk, direct medical cost and life expectancy in patients with diabetes mellitus (DM) are unclear. The aim of this study was to evaluate these associations. / Research Design and Methods: This was a retrospective cohort study that included 208,792 adults with diabetes stratified into 12 disease status groups with varying combinations of heart disease, stroke, moderate CKD (eGFR:30-59ml/min/1.73m2) and severe CKD (eGFR: <30ml/min/1.73m2) in 2008-2010. The effect of risk mortality, annual direct medical costs and life expectancy were assessed using Cox regression, Gamma generalized linear with log link function, and flexible parametric survival models. / Results: Over a median follow-up of 8.5 years (1.6 million patient-years), 50,154 deaths were recorded. Mortality risks for patients with only a single condition among heart disease, stroke and moderate CKD were similar. The mortality risks were 1.75 times, 2.63 times and 3.58 times greater for patients with one, two and all three conditions (consisting of stroke, heart disease and moderate CKD), compared with patients without these diseases, suggesting an independent and individually additive effect for any combination. A similar trend was observed in annual public healthcare costs with 2.91, 3.90 and 3.88 fold increased costs for patients with one, two and three conditions, respectively. Increases in the number of conditions reduced life expectancy greatly, particularly in younger patients. Reduction in life expectancy for a 40-year-old with one, two and three conditions were 20, 25, 30 years for men and 25, 30, 35 years for women. A similar trend of greater magnitude was observed for severe CKD. / Conclusion: The effect of heart diseases, stroke, CKD and the combination of these conditions on all-cause mortality and direct medical costs are independent and cumulative. CKD, especially severe CKD, appears to have a particularly significant impact on life expectancy and direct medical costs in patients with diabetes. These finding supports the importance of preventing both CVD and CKD in patients with DM

Greater variability in lipid measurements associated with kidney diseases in patients with type 2 diabetes mellitus in a 10-year diabetes cohort study.

This study aimed to evaluate the associations between variability of lipid parameters and the risk of kidney disease in patients with type 2 diabetes mellitus. Low-density lipoprotein-cholesterol, total cholesterol to high-density lipoprotein-cholesterol ratio and triglyceride were specifically addressed in this study. This retrospective cohort study included 105,552 patients aged 45-84 with type 2 diabetes mellitus and normal kidney function who were managed under Hong Kong public primary care clinics during 2008-2012. Those with kidney disease (estimated glomerular filtration rate < 60 mL/min/1.73 m2 or urine albumin to creatinine ratio ≥ 3 mg/mmol) were excluded. Variabilities of low-density lipoprotein-cholesterol, total cholesterol to high-density lipoprotein-cholesterol ratio and triglyceride were determined using the standard deviation of the respective parameter obtained from a mixed effects model to minimize regression dilution bias. The associations between lipid variability and renal outcomes including incident kidney disease, renal function decline defined as ≥ 30% reduction in estimated glomerular filtration rate since baseline, and end-stage renal disease (estimated glomerular filtration rate < 15 mL/min/1.73 m2) were evaluated by multivariable Cox regression. After a median follow-up of 66.5 months (0.5 million person-years in total), 49,653 kidney disease, 29,358 renal function decline, and 1765 end-stage renal disease cases were recorded. Positive linear associations between low-density lipoprotein-cholesterol and total cholesterol to high-density lipoprotein-cholesterol ratio variabilities and the risk of all renal outcomes were demonstrated. However, no association between triglyceride variability and any outcome was found. Each mmol/L increase in low-density lipoprotein-cholesterol variability was associated with 20% (Hazard ratio 1.20 [95% CI 1.15-1.25]), 38% (Hazard ratio 1.37 [95% CI 1.30-1.45]), and 108% (Hazard ratio 2.08 [95% CI 1.74-2.50]) higher risk in incident kidney disease, renal function decline and end-stage renal disease respectively. Similarly, each unit increase in total cholesterol to high-density lipoprotein-cholesterol ratio variability was associated with 35% (Hazard ratio 1.15 [95% CI 1.10-1.20]), 33% (Hazard ratio 1.33 [95% CI 1.26-1.40]), and 75% (Hazard ratio 1.75 [95% CI 1.46-2.09]) heightened risk in incident kidney disease, renal function decline and end-stage renal disease respectively. Cholesterol variability may potentially be a useful predictor of kidney diseases in patients with type 2 diabetes mellitus. Attention should be drawn to cholesterol variability when managing diabetic patients and further research is warranted to investigate the modifiable risk factors for lipid variability

Simple Non-laboratory- and Laboratory-based Risk Assessment Algorithms and Nomogram for Detecting Undiagnosed Diabetes Mellitus

Background: To develop a simple nomogram which can be used to predict the risk of diabetes mellitus (DM) in asymptomatic non-diabetic general population based on non-laboratory-based and laboratory-based risk algorithms. Methods: Anthropometric data, plasma fasting glucose, full lipid profile, exercise habit and family history of DM were collected from Chinese non-diabetic subjects aged 18-70. Logistic regression analysis was performed on the data of a random sample of 2518 subjects to construct non-laboratory-based and laboratory-based risk assessment algorithms for the detection of undiagnosed DM; both algorithms were validated on the data of the remaining sample (n=839). Hosmer-Lemeshow χ2 statistic and area under the receiver-operating characteristic curve (AUC) were employed to assess the calibration and discrimination of the different DM risk algorithms. Results: Of 3357 subjects recruited, 271 (8.1%) had undiagnosed DM defined by fasting glucose≥7.0mmol/L or 2-hour post-load plasma glucose≥11.1mmol/L after oral glucose tolerance test. The non-laboratory-based risk algorithm, with score ranging from 0 to 33, included age, body mass index, family history of DM, regular exercise and uncontrolled blood pressure; the laboratory-based risk algorithm, with score ranging from 0 to 37, added triglyceride level to the risk factors. Both algorithms demonstrated acceptable calibration (Hosmer-Lemeshow test: P=0.229 and P=0.483, respectively) and discrimination (AUC: 0.709 and 0.711, respectively) for the detection of undiagnosed DM. The optimal cutoff point on the receiver-operating characteristic curve was 18 for the detection of undiagnosed DM in both algorithms. Conclusions: Simple-to-use nomogram for detecting undiagnosed DM has been developed using the validated non-laboratory-based and laboratory-based risk algorithms.postprin