Development and use of prediction models for classification of cardiovascular risk of remote Indigenous Australians

Background: Cardiovascular disease (CVD) is the leading cause of death for Indigenous Australians. There is widespread belief that current tools have deficiencies for assessing CVD risk in this high-risk population. We sought to develop a 5-year CVD risk score using a wide range of known risk factors to further improve CVD risk prediction in this population. Methods: We used clinical and demographic information on Indigenous people aged between 30 and 74 years without a history of CVD events who participated in the Well Person’s Health Check (WPHC), a community-based survey. Baseline assessments were conducted between 1998 and 2000, and data were linked to administrative hospitalisation and death records for identification of CVD events. We used Cox proportional hazard models to estimate the 5-year CVD risk, and the Harrell’s c-statistic and the modified Hosmer-Lemeshow (mH-L) χ2 statistic to assess the model discrimination and calibration, respectively. Results: The study sample consisted of 1,583 individuals (48.1% male; mean age 45.0 year). The risk score consisted of sex, age, systolic blood pressure, diabetes mellitus, waist circumference, triglycerides, and albumin creatinine ratio. The bias-corrected c-statistic was 0.72 and the bias-corrected mH-L χ2 statistic was 12.01 (p-value, 0.212), indicating good discrimination and calibration, respectively. Using our risk score, the CVD risk of the Indigenous Australians could be stratified to a greater degree compared to a recalibrated Framingham risk score. Conclusions: A seven-factor risk score could satisfactorily stratify 5-year risk of CVD in an Indigenous Australian cohort. These findings inform future research targeting CVD risk in Indigenous Australians

Association of change in daily step count over five years with insulin sensitivity and adiposity: population based cohort study

Objectives: To investigate the association between change in daily step count and both adiposity and insulin sensitivity and the extent to which the association between change in daily step count and insulin sensitivity may be mediated by adiposity. Design: Population based cohort study. Setting: Tasmania, Australia. Participants: 592 adults (men (n=267), mean age 51.4 (SD 12.2) years; women (n=325), mean age 50.3 (12.3) years) who participated in the Tasmanian component of the national AusDiab Study in 2000 and 2005. Main outcome measures: Body mass index, waist to hip ratio, and HOMA insulin sensitivity at follow-up in 2005. Results: Over the five year period, the daily step count decreased for 65% (n=382) of participants. Having a higher daily step count in 2005 than in 2000 was independently associated with lower body mass index (0.08 (95% confidence interval 0.04 to 0.12) lower per 1000 steps), lower waist to hip ratio (0.15 (0.07 to 0.23) lower), and greater insulin sensitivity (1.38 (0.14 to 2.63) HOMA units higher) in 2005. The mean increase in HOMA units fell to 0.34 (-0.79 to 1.47) after adjustment for body mass index in 2005. Conclusions: Among community dwelling, middle aged adults, a higher daily step count at five year follow-up than at baseline was associated with better insulin sensitivity. This effect seems to be largely mediated through lower adiposity

Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses

BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million personyears of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eG FR values 105 mL.min(-1).1.73 m(-2), compared with those with eG FR between 60 and 105 mL.min(-1).1.73 m(-2). Mendelian randomization analyses for CHD showed an association among participants with eGFR 105 mL.min(-1).1.73 m(-2). Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin Alc, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function

Predictors and persistence of foot problems in women aged 70 years and over: A prospective study

Objective: To examine the prevalence and correlates of foot problems in older women over a 6-year period

Is hyperfiltration associated with higher urine albumin-to-creatinine ratio at follow up among Indigenous Australians? The eGFR follow-up study

Background: Glomerular hyperfiltration is not able to be detected in clinical practice. We assessed whether hyperfiltration is associated with albuminuria progression among Indigenous Australians at high risk of diabetes and kidney disease to determine its role in kidney disease progression. Methods: Longitudinal observational study of Indigenous Australians aged ≥18 years recruited from >20 sites, across diabetes and/or kidney function strata. At baseline, iohexol clearance was used to measure glomerular filtration rate (mGFR) and hyperfiltration was defined as (i) a mGFR of ≥125 mL/min/1.73 m , and (ii) an age-adjusted definition, with the top 10% of the mGFR for each 10 year age group at baseline. Baseline and follow-up urine albumin-to-creatinine ratio (uACR) was collected, and linear regression was used to assess the associations of hyperfiltration and uACR at follow up. Results: 407 individuals (33% men, mean age 47 years) were followed-up for a median of 3 years. At baseline, 234 had normoalbuminuria and 173 had albuminuria. Among participants with normoalbuminuria, those with mGFR ≥125 mL/min/1.73 m had 32% higher uACR at follow-up (p = 0.08), and those with age-adjusted hyperfiltration had 60% higher uACR (p = 0.037) compared to those who had normofiltration. These associations were independent of uACR at baseline, but attenuated by HbA . Associations were stronger among those without than those with albuminuria at baseline. Conclusions: Although not available for assessment in current clinical practice, hyperfiltration may represent a marker of subsequent albuminuria progression among individuals who have not yet developed albuminuria

Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses

Background: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. Methods: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. Results: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values 105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR 105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. Conclusions: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function