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Hemoglobin, Albuminuria, and Kidney Function in Cardiovascular Risk: The ARIC (Atherosclerosis Risk in Communities)
Junichi Ishigami1, Morgan E Grams2, Rakhi P Naik3
1Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
Insights
Kidney function and albuminuria are linked to cardiovascular disease (CVD) risk. Anemia and high hemoglobin levels may modify these risks, warranting further investigation into their interactions.
Area of Science:
- Nephrology
- Cardiology
- Hematology
Background:
- Reduced estimated glomerular filtration rate (eGFR) and elevated urinary albumin-to-creatinine ratio (ACR) are known risk factors for cardiovascular disease (CVD).
- The influence of abnormal hemoglobin levels (both low and high) on the association between kidney function markers and CVD risk is not fully understood.
Purpose of the Study:
- To investigate the cross-sectional associations of eGFR and ACR with hemoglobin levels.
- To examine the longitudinal associations of eGFR, ACR, and hemoglobin levels with CVD risk.
Main Methods:
- Analysis of 5801 participants from the ARIC study (1996-1998) with longitudinal follow-up through 2013.
- Assessment of baseline hemoglobin, eGFR, and ACR, and incident CVD events (heart failure, coronary heart disease, stroke).
- Multivariable Cox models were used to evaluate associations and interactions.
Main Results:
- Anemia (8.8%) and high hemoglobin (7.2%) were prevalent at baseline.
- Lower eGFR and higher ACR were associated with anemia and high hemoglobin.
- Lower eGFR, higher ACR, and anemia were independently associated with increased CVD risk.
- A potential interaction was observed between high ACR and high hemoglobin for coronary heart disease and stroke risk.
Conclusions:
- Kidney function, albuminuria, and anemia are independently associated with CVD risk.
- The interplay between albuminuria and high hemoglobin warrants further research for atherosclerotic CVD risk.
Background:
Reduced estimated glomerular filtration rate (eGFR) and elevated urinary albumin-to-creatinine ratio (ACR) individually increase risk of cardiovascular disease (CVD). We hypothesized that these associations are stronger among people with abnormal (both low and high) hemoglobin levels.
Methods And Results:
Using 5801 participants with available hemoglobin measures of the ARIC (Atherosclerosis Risk in Community) study in 1996-1998, we explored the cross-sectional association of eGFR and ACR with hemoglobin levels and their longitudinal associations with CVD (heart failure, coronary heart disease, and stroke) risk through 2013. At baseline, 8.8% had anemia (<13 g/dL in men and <12 g/dL in women) and 7.2% had high hemoglobin (≥16 g/dL in men and ≥15 g/dL in women). The adjusted prevalence ratio of anemia was 2.12 (95% confidence interval, 1.59-2.82) for eGFR 30 to 59 compared with ≥90 mL/min per 1.73 m2 and 1.45 (1.07-1.95) for ACR ≥30 compared with <10 mg/g. ACR ≥30 mg/g was also associated with high hemoglobin (prevalence ratio, 1.57 [1.12-2.19] compared with <10 mg/g). During follow-up, there were 1069 incident CVDs among 5098 CVD-free participants at baseline. In multivariable Cox models, lower eGFR, higher ACR, and anemia were each independently associated with CVD risk, with the association of low eGFR being slightly stronger in anemia (P-for-interaction, 0.072). There was no hemoglobin-ACR interaction; however, when CVD subtypes were analyzed separately, risk of coronary heart disease and stroke associated with high ACR was slightly stronger in high hemoglobin (P-for-interaction, 0.074).
Conclusions:
Kidney function, albuminuria, and anemia were correlated and independently associated with CVD risk. Correlation and potential interaction for atherosclerotic CVD between albuminuria and high hemoglobin deserve further investigation.
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