Relationship between Blood Pressure and Chronic Kidney Disease in the Japanese Population: The Lower the Better Even in Individuals without Hypertension?

213 Hypertens Res Vol.31 (2008) No.2 p.213-219 Original Article Relationship between Blood Pressure and Chronic Kidney Disease in the Japanese Population: The Lower the Better Even in Individuals without Hypertension? Yasutomi HIGASHIKUNI1), Nobukazu ISHIZAKA1), Yuko ISHIZAKA2), Ei-ichi TODA2), Ryozo NAGAI1), and Minoru YAMAKADO2) In hypertensive subjects, it has been demonstrated that the lower the blood pressure, the lower the incidence of chronic kidney disease (CKD). However, whether this relationship holds true in individuals without hypertension—that is, in individuals with a blood pressure < 140/90 mmHg—remains unknown. This study was performed to assess the relationship between blood pressure and CKD in a Japanese population without hypertension. Among 13,007 Japanese participants in a general health screening, 9,596 (5,691 men and 3,905 women) were found to have either normal blood pressure or prehypertension, and were enrolled in this study. We categorized these individuals’ blood pressure into six classes: BP-C1, < 90/< 65 mmHg; BPC2, 90–100/65–70 mmHg; BP-C3, 100–110/70–75 mmHg; BP-C4, 110–120/75–80 mmHg; BP-C5, 120–130/80– 85 mmHg; and BP-C6, 130–140/85–90 mmHg. Albuminuria was defined as a urinary albumin excretion ratio of ≥ 30 mg/g. Low estimated glomerular filtration rate (eGFR) was defined as eGFR < 60 mL/min/1.73 m2. In men, when BP-C3 was used as a reference, multivariate logistic regression analysis adjusted for age, body mass index, serum lipid profiles, fasting plasma glucose and smoking status showed that BP-C1, BP-C2, BP-C4, BP-C5 and BP-C6 were associated with albuminuria with an adjusted odds ratio of 1.85 (0.53–6.46), 1.22 (0.59–2.51), 1.62 (1.01–2.59), 2.57 (1.64–4.02), and 3.81 (2.44–5.96). In women, the adjusted odds ratios of the risk for albuminuria in BP-C2, BP-C3, BP-C4, BP-C5 and BP-C6, as compared with BP-C1 as a reference, were 1.83 (0.70–4.79), 2.13 (0.84–5.42), 2.80 (1.10–7.14), 2.59 (0.99–6.78), and 3.99 (1.50–10.64). Blood pressure was not significantly associated with low eGFR in either gender. The risk for albuminuria was significantly greater when blood pressure exceeded 110/75 mmHg in both genders. (Hypertens Res 2008; 31: 213–219) Key Words: blood pressure, chronic kidney disease, Japanese population Introduction The increasing prevalence of end-stage renal disease (ESRD) that may require hemodialysis is now a worldwide public health problem because of poor outcomes and high costs. To prevent an increase in the number of ESRD patients, intensive intervention at an early stage of kidney impairment has recently been emphasized. This enthusiasm has led to the establishment of the concept of chronic kidney disease (CKD). According to the National Kidney Foundation (NKF) Kidney Disease Outcomes Quality Initiative (K/DOQI) crite- From the 1)Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Tokyo, Japan; and 2)Center for Multiphasic Health Testing and Services, Mitsui Memorial Hospital, Tokyo, Japan. Address for Reprints: Nobukazu Ishizaka, M.D., Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, 7–3–1 Hongo, Bunkyo-ku, Tokyo 113–0033, Japan. E-mail: Received May 22, 2007; Accepted in revised form August 24, 2007. 214 Hypertens Res Vol. 31, No. 2 (2008) Table 1. Characteristics of the Enrolled Male Subjects According to Blood Pressure Levels Total (n=5,691) BP-C1 (n=67) BP-C2 (n=401) BP-C3 BP-C4 BP-C5 BP-C6 (n=1,130) (n=1,565) (n=1,140) (n=1,088) p value Age, years old 52.2±10.5 53.4±11.9 51.0±10.8 50.8±10.6 51.3±10.5 53.2±10.4 54.2±11.9 <0.0001 BMI, kg/m2 23.3±2.7 20.9±2.1 21.8±2.2 22.5±2.3 23.1±2.5 23.8±2.7 24.3±2.9 <0.0001 Systolic BP, mmHg 116.3±11.9 85.5±3.5 95.6±3.0 104.9±3.0 114.0±3.2 123.0±3.9 132.2±4.7 <0.0001 Diastolic BP, mmHg 74.3±7.9 56.4±4.0 62.5±4.3 67.6±4.1 72.8±4.3 78.3±4.3 83.6±4.5 <0.0001 TC, mg/dL 206.7±32.2 208.2±32.9 200.0±31.3 202.8±32.6 206.9±32.1 208.4±31.9 210.3±31.9 <0.0001 HDL-C, mg/dL 55.0±13.4 60.4±16.5 55.0±13.4 55.2±12.9 55.2±13.9 54.8±13.0 54.7±13.6 0.032 LDL-C, mg/dL 127.2±30.6 125.3±38.2 123.8±30.5 125.4±30.6 127.6±30.3 127.5±30.9 129.2±29.9 0.017 TG, mg/dL 128.0±88.7 108.9±96.1 106.9±58.2 113.8±73.6 127.5±97.0 136.7±96.9 140.6±84.4 <0.0001 Hyperglycemia, n (%) 698 (12.3%) 6 (9.0%) 30 (7.5%) 78 (6.9%) 175 (11.2%) 212 (14.7%) 197 (18.1%) <0.0001 Fasting plasma glucose, mg/dL 98.1±19.3 96.6±24.2 94.2±16.9 94.9±15.5 97.6±19.2 99.4±17.7 102.2±24.0 <0.0001 HbA1c, % 5.34±0.72 5.43±0.91 5.28±0.68 5.26±0.62 5.33±0.69 5.36±0.68 5.44±0.86 <0.0001 Smoking status <0.0001 Former smoking, n (%) 1,849 (32.5%) 17 (25.4%) 95 (23.7%) 316 (28.0%) 496 (31.7%) 496 (34.4%) 429 (39.4%) Current smoking, n (%) 1,893 (33.3%) 32 (47.8%) 183 (45.6%) 402 (35.6%) 522 (33.4%) 440 (30.6%) 314 (28.9%) UAER, mg/g 14.1±73.7 9.1±22.0 11.1±72.4 8.0±33.5 11.5±50.3 19.8±117.8 18.0±56.3 0.0005 Albuminuria, n (%) 331 (5.8%) 3 (4.5%) 11 (2.7%) 26 (2.3%) 65 (4.2%) 102 (7.1%) 124 (11.4%) <0.0001 eGFR, mL/min/1.73 m2 70.7±9.9 71.5±11.3 71.3±9.9 71.3±9.8 70.8±9.6 70.5±10.0 70.1±9.9 0.055 Low eGFR, n (%) 735 (12.9%) 9 (13.4%) 42 (10.5%) 131 (11.6%) 189 (12.1%) 206 (14.3%) 158 (14.5%) 0.078 BMI, body mass index; BP, blood pressure; eGFR, estimated glomerular filtration rate; HbA1c, hemoglobin A1c; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; TC, total cholesterol; TG, triglyceride; UAER, urinary albumin excretion ratio. ria, CKD is defined as an estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73 m2 and/or kidney damage identified mainly by microalbuminuria (1). Hypertension is a well-known risk factor for the progression of renal and cardiovascular diseases (2–5). Previous studies have demonstrated that lower blood pressure leads to better clinical outcomes in regard to renal and cardiovascular diseases (2, 6–10), thereby providing the academic basis of “the lower the better” strategy in daily practice. Only a few studies, however, have evaluated the relationship between blood pressure and CKD in the non-hypertensive range of blood pressure. Haroun et al. (10) demonstrated that a blood pressure of 130–140/85–90 mmHg was associated with an increase in serum creatinine levels in a predominantly Caucasian population. Ramirez et al. (4) showed that the risk for proteinuria was significantly increased at a systolic blood pressure of 130–140 mmHg in a Chinese population, whereas a significant increase in the risk for proteinuria was not found at a blood pressure level below 140/90 mmHg in a Malaysian population. In the current study, we sought to assess the relationship between blood pressure level and CKD in Japanese individuals without hypertension. We used albuminuria and low eGFR as indicators of CKD, and the two indicators were evaluated separately so that the pathophysiology of kidney damage could be clearly assessed. Methods Study Subjects The study was approved by the Ethical Committee of Mits (...truncated)