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. 2024 Dec 4;31(17):2046-2055.
doi: 10.1093/eurjpc/zwae189.

The relationship between low levels of albuminuria and mortality among adults without major cardiovascular risk factors

Sophie E Claudel  1   2 , Sushrut S Waikar  2   3 , Insa M Schmidt  3   4 , Ramachandran S Vasan  2   5 , Ashish Verma  2   3
Affiliations

The relationship between low levels of albuminuria and mortality among adults without major cardiovascular risk factors

Sophie E Claudel et al. Eur J Prev Cardiol. .

Abstract

Aims: The aim of this study is to determine whether elevated levels of albuminuria within the low range [urinary albumin-to-creatinine ratio (UACR) <30 mg/g] are linked to cardiovascular death in adults lacking major cardiovascular risk factors.

Methods and results: The association between UACR and cardiovascular mortality was investigated among 12 835 participants in the 1999-2014 National Health and Nutrition Examination Survey using Cox proportional hazard models and confounder-adjusted survival curves. We excluded participants with baseline cardiovascular disease, hypertension, diabetes, pre-diabetes, an estimated glomerular filtration rate <60 mL/min/1.73 m2, currently pregnant, and those who received dialysis last year. Over a median follow-up of 12.3 years, 110 and 621 participants experienced cardiovascular and all-cause mortality. In multivariable-adjusted models, each doubling of UACR was associated with a 36% higher risk of cardiovascular death [hazard ratio (HR) 1.36, 95% confidence interval (CI) 1.02-1.82] and a 24% higher risk of all-cause mortality (HR 1.24, 95% CI 1.10-1.39). The 15-year adjusted cumulative incidences of cardiovascular mortality were 0.91, 0.99, and 2.1% for UACR levels of <4.18, 4.18 to <6.91, and ≥6.91 mg/g, respectively. The 15-year adjusted cumulative incidences of all-cause mortality were 5.1, 6.1, and 7.4% for UACR levels of <4.18, 4.18 to <6.91, and ≥6.91 mg/g, respectively.

Conclusion: Adults with elevated levels of albuminuria within the low range (UACR <30 mg/g) and no major cardiovascular risk factors had elevated risks of cardiovascular and all-cause mortality. The risk increased linearly with higher albuminuria levels. This emphasizes a risk gradient across all albuminuria levels, even within the supposedly normal range, adding to the existing evidence.

Keywords: Albuminuria; All-cause mortality; Cardiovascular mortality; Low-grade albuminuria; NHANES; UACR.

Plain language summary

In this study of 12 835 adults without major cardiovascular risk factors (such as hypertension, cardiovascular disease, diabetes, pre-diabetes, or chronic kidney disease), we investigated the association between higher albuminuria levels within the low range [urine albumin-to-creatinine ratio (UACR) <30 mg/g] and both cardiovascular and all-cause mortality. Our findings revealed a linear increase in excess risk for both outcomes with rising albuminuria among relatively healthy adults. Each doubling of albuminuria was associated with a 36% higher risk of cardiovascular death [hazard ratio (HR) 1.36, 95% confidence interval (CI) 1.02–1.82] and a 24% higher risk of all-cause mortality (HR 1.24, 95% CI 1.10–1.39). Each 10 mg/g increase in albuminuria was associated with a 66% higher risk of cardiovascular mortality (HR 1.66, 95% CI 1.20–2.28) and a 41% higher risk of all-cause mortality (HR 1.41, 95% CI 1.17–1.68). These results challenge the assumption that UACR values below 30 mg/g are non-prognostic in adults without major cardiovascular risk factors.

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Conflict of interest statement

Conflict of interest: none declared.

Figures

Figure 1
Figure 1
Adjusted cumulative incidences for (A) cardiovascular mortality and (B) all-cause mortality among urinary albumin-to-creatinine ratio tertiles at 10 and 15 years of follow-up in individuals with low levels of albuminuria.
Figure 2
Figure 2
Restricted cubic splines. Linear relationship between urinary albumin-to-creatinine ratio and (A) cardiovascular mortality and (B) non-cardiovascular mortality. The P-value for linearity is <0.0001 for all. The restricted cubic spline model was fitted using 3 knots at 25, 50, and 75 percentiles of urinary albumin-to-creatinine ratio and reflects multivariable model adjusted for age, sex, race or ethnicity, insurance, smoking, survey year, body mass index, food security, haemoglobin A1c, total cholesterol, systolic blood pressure, serum albumin, statin use, and estimated glomerular filtration rate. UACR, urinary albumin-to-creatinine ratio.
Figure 3
Figure 3
Adjusted cumulative incidences of (A) cardiovascular and (B) all-cause mortality at 15 years by baseline urinary albumin-to-creatinine ratio.
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