Research Article: High-normal albuminuria is associated with subclinical atherosclerosis in male population with estimated glomerular filtration rate ≥60 mL/min/1.73 m2: A cross-sectional study

Date Published: August 1, 2019

Publisher: Public Library of Science

Author(s): Tomoe Kimura, Toshinori Ueno, Shigehiro Doi, Ayumu Nakashima, Toshiki Doi, Aki Ashitani, Reo Kawano, Kiminori Yamane, Takao Masaki, Tatsuo Shimosawa.


Low-grade albuminuria has been considered a predictor of cardiovascular mortality. We investigated the relationship between high-normal albuminuria and subclinical atherosclerosis in non-diabetic men with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2.

In this cross-sectional study, 1,756 men with eGFR ≥60 mL/min/1.73 m2 and urine albumin-to-creatinine ratio (UACR) <30 mg/g, who attended general health checkups between April 2012 and March 2015, underwent blood sampling, urinalysis, and carotid ultrasonography. We excluded the subjects who were diabetic and/or received an anti-hypertensive drug. Carotid intima-media thickness (IMT) and the number of focal atheromatous plaques were used as indicators of subclinical atherosclerosis. Multiple linear regression analysis was performed to identify clinical factors associated with carotid IMT. Poisson regression analysis was used to assess the determinants of the carotid plaque number. Median UACR was 4.8 mg/g (interquartile range, 3.6–6.9 mg/g). Compared with subjects with low-normal UACR (<10.0 mg/g), subjects with high-normal UACR (10.0–29.8 mg/g) had greater IMT and higher carotid plaque number. High-normal UACR was independently associated with thickened IMT in the model adjusted for conventional cardiovascular disease risk factors. Moreover, participants with high-normal UACR were also more likely to be associated with increased plaque count (prevalence ratio: 1.06; 95% confidence interval: 1.01–1.14) after adjustment for conventional cardiovascular disease risk factors. Our results indicate that high-normal albuminuria is associated with both carotid IMT and plaque formation in the non-diabetic male population with eGFR ≥60 mL/min/1.73 m2.

Partial Text

Atherosclerosis is a state whereby the inside of an artery hardens and narrows [1]. Even without symptoms in the early phase, atherosclerosis eventually causes severe cardiovascular disease (CVD) such as coronary heart disease and stroke. Currently the impact of atherosclerosis is estimated at 422.7 million CVD events and 17.9 million CVD deaths worldwide [2], confirming its consideration as a major health problem. According to previous studies, carotid atherosclerosis correlates with not only coronary and cerebral atherosclerosis, but also incidence of CVD [3, 4]. Subsequently, carotid intima-media thickness (IMT) and the extent of atheromatous carotid plaque measured by ultrasonography have become well-established methods for the evaluation of atherosclerosis [5]. In the clinical setting, carotid duplex is mainly performed in subjects with a risk factor for CVD, including smoking, obesity, hypertension, diabetes, and dyslipidemia [6]. Nonetheless many people still die of CVD; therefore, unconventional risk factors should also be determined for the early evaluation of atherosclerosis.

Characteristics of 1,756 men with mean age of 51.5 ± 7.6 years are shown in Table 1. The median UACR of the subjects was 5.1 mg/g (3.6–8.1 mg/g). In the group with high-normal UACR, age (p < 0.001), BMI (p < 0.001), current smoking rate (p = 0.047), systolic BP (p < 0.001), diastolic BP (p < 0.001), presence of hematuria (p < 0.001), as well as the levels of HbA1c (p = 0.006), HOMA-IR (p < 0.001), urinary acid (p = 0.03), total cholesterol (p = 0.01), triglycerides (p = 0.005), CRP (p < 0.001), and eGFR (p = 0.012) were all significantly greater than in the group with low-normal UACR. In the present study, we conducted a cross-sectional analysis using data of medical examinations from 1,756 Japanese men with eGFR ≥60 mL/min/1.73 m2 and UACR <30 mg/g. We have demonstrated that in this population, high-normal albuminuria is associated with thickened IMT and increased carotid plaque number. Moreover, we show that this association is independent of conventional CVD risk factors. Our results indicate that the population with a UACR of 10–29.9 mg/g exhibit subclinical atherosclerotic changes even though a UACR of less than 30 mg/g is regarded as being low risk for CVD.   Source: