A Newly Estimated Glomerular Filtration Rate Is Independently Associated with Arterial Stiffness in Japanese Patients

193 Hypertens Res Vol.31 (2008) No.2 p.193-201 Original Article A Newly Estimated Glomerular Filtration Rate Is Independently Associated with Arterial Stiffness in Japanese Patients Naoki NAKAGAWA1),2), Fumihiko TAKAHASHI2), Junko CHINDA2), Motoi KOBAYASHI2), Yoshikazu HAYASHI2), Masahiko ABE2), Yasuaki SAIJO3), Kenjiro KIKUCHI1), and Naoyuki HASEBE1) Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular disease, and thus is a major worldwide public health problem. Recently, an estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease equation for Japanese patients was proposed by the Japanese Society of Nephrology. However, the role of eGFR in the assessment of atherosclerosis is not well understood in Japanese patients. We analyzed the relationship between eGFR and severity of arterial stiffness using brachial-ankle pulse wave velocity (baPWV) in 647 adult Japanese patients. baPWV correlated significantly and positively with age, hypertension, diabetes, prior cardiovascular disease, blood pressure, pulse pressure and heart rate, and negatively with eGFR (r = – 0.405, p < 0.0001). A multiple regression analysis revealed that baPWV correlated independently with eGFR. Furthermore, there was a stepwise increase in baPWV, corresponding to advances in CKD through stages 1 to 5. When CKD stage 3 was divided at eGFR 45 mL/min/ 1.73 m2, the baPWV of stage 3b (eGFR 30 to 44) was significantly higher than that of stage 3a (eGFR 45 to 59) independent of traditional risk factors, suggesting that an eGFR of 45 mL/min/1.73 m2 may be a critical cut off value to predict arterial stiffness in CKD. In conclusion, the newly proposed eGFR is significantly associated with arterial stiffness, independent of traditional risk factors for cardiovascular disease. (Hypertens Res 2008; 31: 193–201) Key Words: chronic kidney disease, estimated glomerular filtration rate, arterial stiffness, cross-sectional studies, Japanese patients Introduction Chronic kidney disease (CKD) is a major worldwide public health problem, with adverse outcomes of kidney failure, cardiovascular disease (CVD), and premature death (1–3). A number of prospective epidemiologic studies have shown that patients with CKD are at increased risk for CVD, independent of conventional cardiovascular risk factors (4–6). Thus, the National Kidney Foundation formed a task force to heighten awareness of CVD in CKD (7), and defined CKD as either 1) kidney damage for ≥ 3 months, confirmed by kidney biopsy or markers of kidney damage, with or without a decrease in glomerular filtration rate (GFR), or 2) GFR < 60 mL/min/1.73 m2 for ≥ 3 months, with or without kidney damage (8). Pulse wave velocity (PWV) is known to be an indicator of arterial stiffness (9, 10), and an independent predictor of cardiovascular events in patients with end-stage renal disease (11, 12). A simple and noninvasive method to automatically measure brachial-ankle PWV (baPWV) was recently developed to From the 1)Cardiovascular Division, Department of Internal Medicine and 3)Department of Health Science, Asahikawa Medical College, Asahikawa, Japan; and 2)Department of Internal Medicine, Hokkaido Prefectural Haboro Hospital, Hokkaido, Japan. Address for Reprints: Naoki Nakagawa, M.D., Cardiovascular Division, Department of Internal Medicine, Asahikawa Medical College, 2–1–1–1 Midorigaoka-higashi, Asahikawa 078–8510, Japan. E-mail: Received March 28, 2007; Accepted in revised form August 16, 2007. 194 Hypertens Res Vol. 31, No. 2 (2008) Table 1. Baseline Characteristics N Age (years) BMI (kg/m2) Hypertension (n (%)) Diabetes (n (%)) Dyslipidemia (n (%)) Smoking (n (%)) Prior CVD (n (%)) baPWV (cm/s) Systolic BP (mmHg) Diastolic BP (mmHg) Pulse pressure (mmHg) Mean BP (mmHg) HR (bpm) Hb (g/dL) Total cholesterol (mg/dL) Triglycerides (mg/dL) (n=607) HDL-C (mg/dL) (n=606) LDL-C (mg/dL) (n=605) Uric acid (mg/dL) (n=604) HbA1c (%) (n=278) Serum creatinine (mg/dL) eGFR (mL/min/1.73 m2) Men Women Total 318 65.9±12.4 25.6±3.7 251 (79) 117 (37) 163 (51) 153 (48) 81 (25) 1,782±376 142±19 83±10 59±13 103±12 68±12 14.3±1.7 180±34 151±120 53±15 104±26 5.9±1.4 6.3±1.4 0.97±0.79 66.1±16.1 329 66.6±11.0 26.3±4.3 265 (81) 112 (34) 223 (68) 40 (12) 32 (11) 1,768±374 144±18 81±10 63±14 102±12 70±11 13.1±1.3 188±32 125±65 59±16 110±28 4.8±1.3 6.3±1.2 0.72±0.33 60.9±12.7 647 66.3±11.7 25.9±4.0 516 (80) 229 (35) 386 (60) 193 (30) 113 (18) 1,775±375 143±19 82±10 61±14 102±12 69±12 13.7±1.6 184±33 138±96 56±16 107±28 5.3±1.4 6.3±1.3 0.84±0.61 63.4±14.5 Variables are presented as mean±SD, or number and percentage. BMI, body mass index; CVD; cardiovascular disease; baPWV, brachial-ankle pulse wave velocity; BP, blood pressure; HR, heart rate; eGFR, estimated glomerular filtration rate. screen large populations (13, 14). In several reports that included patients with different stages of CKD, PWV increased proportionally to decreased estimated GFR (eGFR) or creatinine clearance (15–17). Recently, an eGFR for Japanese patients was proposed by the Japanese Society of Nephrology (18); however, its clinical usefulness has not yet been fully established. In this study, we investigated for the first time the significance of eGFR as an index and predictor of arterial stiffness in Japanese patients to clarify whether CKD is related to the progression of arterial stiffness in such patients. Methods Subjects Subjects were 647 consecutive patients (318 men and 329 women; aged 15 to 92 years), who underwent baPWV at Hokkaido Prefectural Haboro Hospital from January 2005 to April 2006. Patients on hemodialysis or with an ankle brachial pressure index (ABI) of ≤ 0.9 were excluded. Age, gender, lipid parameters, and conventional cardiovascular risk factors were recorded. Body weight and height were measured during the examination in light indoor clothing without shoes. baPWV, ABI, heart rate (HR), and blood pressure (BP) were measured with a pulse pressure analyzer (model: BP203RPE II; Nihon Colin, Tokyo, Japan) as described previously (13, 14). PWV was expressed in cm/s. Fasting or nonfasting blood samples were drawn from the antecubital vein of seated participants with minimal tourniquet use. Samples were collected into vacuum tubes containing ethylenediaminetetraacetic acid for Hb and HbA1c measurement, or a serum separator gel for serum creatinine, total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, and uric acid measurement. A history of smoking was defined as > 10 pack-years. Hypertension was defined as either systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, or current use of antihypertensive medications. Diabetes was defined as one of the following: fasting blood sugar ≥ 126 mg/dL; non-fasting blood sugar ≥ 200 mg/dL or HbA1c ≥ 6.5%; or current use of insulin or an oral hypoglycemic agent. Dyslipidemia was defined as: TC ≥ 220 mg/dL; HDL cholest (...truncated)