Urinary Albumin-to-Creatinine Ratio in Normal Range, Cardiovascular Health, and All-Cause Mortality

Key Points Question Does cardiovascular health (CVH) modify the association of all-cause mortality with elevated urinary albumin-to-creatinine ratio (UACR) within the normal range (<30 mg/g)? Findings In this cohort study of 23 697 US adults with a UACR less than 30 mg/g, the risk of all-cause mortality associated with a high-normal UACR gradually increased across CVH groups as delineated by Life’s Essential 8 scores. Participants with poor CVH status and high-normal UACR had the highest risk of all-cause mortality. Meaning The findings suggest that maintaining ideal CVH may reduce the risk of all-cause mortality associated with high-normal UACR, highlighting the importance of risk management for early kidney dysfunction.


eMethods. Information on Collection and Measurements for the Components of CVH
Diet quality was assessed by the Healthy Eating Index 2015 (HEI-2015), and the data for Diet quality assessment came from the "Food Patterns Equivalents Database 14". 1 Physical activity was calculated by self-reported moderate or greater activity frequency per week and duration.According to the AHA, each minute of moderate exercise counts as one unit, while each minute of vigorous activity counts as two units. 2Nicotine exposure was determined based on self-reported consumption of any nicotine product in the past 30 days, and secondhand nicotine exposure in a participant's household.Sleep duration was the average sleep duration per day.Body mass index was determined as weight (kg) divided by height squared (m²).
Blood pressure was assessed by three consecutive times of systolic and diastolic measurements and the use of antihypertensive drugs.Blood samples were obtained at a mobile examination center and transmitted to a central laboratory to analyze plasma total and high-density lipoprotein (HDL) cholesterol, fasting blood glucose (FBG), and haemoglobin A1c (HbA1c).Lipid was assessed by plasma total and HDL cholesterol as well as the use of lipid-lowering medications.Blood glucose was assessed by FBG or HbA1c or history of diabetes.The multivariable Cox regression model adjusted for age; sex; race and ethnicity; education level; marital status; poverty income ratio; estimated glomerular filtration rate; and history of heart disease, stroke, cancer; hypertension; and diabetes.CVH, cardiovascular health; HR, hazard ratio; UACR, urinary albumin-to-creatinine ratio.

eFigure 1 .
Selection of Study Participants From the 2005 to 2018 Cycles of the National Health and Nutrition Examination Survey eFigure 2. HRs (95% CIs) for Associations of UACR With All-Cause Mortality Stratified by CVH Groups, After Adjusting for Hypertension and Diabetes

eTable 1. Definition and Scoring Approach for the American Heart Association's Life's Essential 8 Score 2
pressure Metric: Systolic and diastolic blood pressure (mm Hg) Abbreviation: CVH, cardiovascular health; NDS, nicotine-delivery systems; HDL, high-density lipoprotein; FBG, fasting blood glucose; HbA1c, glycated hemoglobin; HTN, hypertension.Note: This table is adapted from Life's Essential 8: Updating and Enhancing the American Heart Association's Construct of Cardiovascular Health: A Presidential Advisory From the American Heart Association. 2 eTable 2.

Cardiovascular Health Metrics Based on UACR Levels in NHANES 2005-2018 a
Abbreviation: UACR, urinary albumin-to-creatinine ratio.aDatawere presented as weighted mean (SD).bBlood lipids used the level of non-HDL cholesterol according to the AHA definitions of Life's Essential 8. eTable 3.

Comparisons of Baseline Characteristics Between Participants With Complete Data and Those With Missing CVH Data No. (%) of participants a P-value
Abbreviation: CVH, cardiovascular health.aAll estimates are not accounted for complex survey design, due to participants without CVH data lack of the MEC exam weight.bOther race includes American Indian or Alaska Native, Asian, Native Hawaiian or Pacific Islander, multiple races or ethnicities, or unknown.eTable 4.

Adjusted Hazard Ratios and 95% CIs of CVH With Risk of All-Cause Mortality HR (95% CI)
Adjusted for age, sex, education level, poverty income ratio, marital status, race and ethnicity, estimated glomerular filtration rate.Adjusted for age; sex; education level; poverty income ratio; marital status; race and ethnicity; estimated glomerular filtration rate; and history of heart disease, stroke, and cancer.

Adjusted Hazard Ratios and 95% CIs of UACR With Risk of All-Cause Mortality Stratified by Sex and CVH
Abbreviation: CVH, cardiovascular health; UACR, Urinary albumin-to-creatinine ratio; HR, hazard ratio; CI, confidence interval.aAdjusted for age; sex; education level; poverty income ratio; marital status; race and ethnicity; estimated glomerular filtration rate; and history of heart disease, stroke, and cancer.eTable 6.

Adjusted Hazard Ratios and 95% CIs of UACR With Risk of All-Cause Mortality Stratified by Age and CVH
Abbreviation: CVH, cardiovascular health; UACR, Urinary albumin-to-creatinine ratio; HR, hazard ratio; CI, confidence interval.aAdjusted for age; sex; education level; poverty income ratio; marital status; race and ethnicity; estimated glomerular filtration rate; and history of heart disease, stroke, and cancer.eTable 7.

Adjusted Hazard Ratios and 95% CIs of UACR With Risk of All-Cause Mortality Stratified by Hypertension and CVH
Abbreviation: CVH, cardiovascular health; UACR, Urinary albumin-to-creatinine ratio; HR, hazard ratio; CI, confidence interval.aAdjusted for age; sex; education level; poverty income ratio; marital status; race and ethnicity; estimated glomerular filtration rate; and history of heart disease, stroke, and cancer.eTable 8.

Adjusted Hazard Ratios and 95% CIs of UACR With Risk of All-Cause Mortality Stratified by Diabetes and CVH
Abbreviation: CVH, cardiovascular health; UACR, Urinary albumin-to-creatinine ratio; HR, hazard ratio; CI, confidence interval.aAdjusted for age; sex; education level; poverty income ratio; marital status; race and ethnicity; estimated glomerular filtration rate; and history of heart disease, stroke, and cancer.b NA, not available for HR(95%CI) since failure to converge in modeling with limited sample size.eTable 9.

Adjusted Hazard Ratios and 95% CIs of UACR With Risk of All-Cause Mortality Stratified by CVH After Excluding Death Within the First 2 years of Follow-Up
eTable 12.

Adjusted Hazard Ratios and 95% CIs of UACR With Risk of All-Cause Mortality Stratified by CVH With Additional Adjustment for Hypertension and Diabetes
eTable 13.

Estimated Direct and Indirect Effect Sizes of Cardiovascular Health With All-Cause Mortality Through UACR in the National Health and Nutrition Examination Survey, 2005 to 2018
Abbreviation: CVH, cardiovascular health; UACR, Urinary albumin-to-creatinine ratio; HR, hazard ratio; CI, confidence interval.a Adjusted for age; sex; education level; poverty income ratio; marital status; race and ethnicity; estimated glomerular filtration rate; and history of heart disease, stroke, and cancer.