Adiponectin Levels Associated with the Development of Hypertension: A Prospective Study

229 Hypertens Res Vol.31 (2008) No.2 p.229-233 Original Article Adiponectin Levels Associated with the Development of Hypertension: A Prospective Study Takuya IMATOH1), Motonobu MIYAZAKI2), Yoshito MOMOSE1), Shinichi TANIHARA1), and Hiroshi UNE1) Adiponectin is a recently discovered protein that seems to be exclusively secreted by adipocytes and is the most abundant adipose tissue–derived protein. While some recent studies have demonstrated an association between adiponectin levels and hypertension, these studies were cross-sectional in design, and the results have been inconsistent. Therefore we performed a prospective study to elucidate the role of adiponectin in the development of hypertension. The results of this study showed that serum adiponectin levels were significantly lower in hypertensive subjects than in normotensive subjects. Moreover, in logistic regression analysis, the subjects in the lowest quartile had a 3.72-fold higher risk than those in the highest quartile. Even after adjusting for potential confounding factors, this association was found to be significant. Low serum adiponectin levels were found to be independently associated with a higher risk for the development of hypertension. Our results therefore suggest that hypoadiponectinemia is a novel predictor of hypertension. (Hypertens Res 2008; 31: 229–233) Key Words: hypertension, adiponectin, prospective study, epidemiological study Introduction The latest World Health Organization (WHO) projections indicate that approximately 1.6 billion adults (aged ≥ 15 years) are overweight and at least 400 million adults are obese. WHO further estimates that by 2015, approximately 2.3 billion adults will be overweight and more than 700 million will be obese. Because obese individuals are at risk of diabetes, hypertension, arteriosclerosis and other cardiovascular diseases, obesity and obesity-related diseases are a worldwide public health problem. Adipose tissue is involved in regulating a variety of homeostatic processes as an endocrine organ that secretes many biologically active molecules. Adiponectin is a recently discovered protein that seems to be exclusively secreted by adipocytes and is the most abundant adipose tissue–derived protein (1, 2). Plasma adiponectin levels in humans are lower in obese than in non-obese subjects, in patients with coronary artery disease and diabetes mellitus type 2 than in healthy subjects, higher in women than in men. A recent study reported that hypoadiponectinemia was significantly and independently associated with metabolic syndrome (3, 4) and cardiovascular disease (5–8). Hypertension is also a major trigger of cardiovascular complications and is associated with endothelial dysfunction and atherosclerosis. Though several cross-sectional studies have shown that adiponectin correlates negatively with blood pressure, the results of studies on the relation between adiponectin and hypertension have been inconsistent. Some recent studies have demonstrated an association between adiponectin levels and hypertension (9–16), but almost all these studies were From the 1)Department of Hygiene and Preventive Medicine, School of Medicine, Fukuoka University, Fukuoka, Japan; and 2)Department of Health and Welfare, Saitama City Government, Saitama, Japan. Address for Reprints: Takuya Imatoh, Department of Hygiene and Preventive Medicine, School of Medicine, Fukuoka University, 7–45–1, Nanakuma, Jonan-ku, Fukuoka 814–0180, Japan. E-mail: Received May 1, 2007; Accepted in revised form September 2, 2007. 230 Hypertens Res Vol. 31, No. 2 (2008) Table 1. Baseline Demographic and Clinical Characteristics of Study Population Based on Serum Adiponectin Level Quartiles Characteristics Follow-up period, years Age, years Smoking status, n (%) Non-smokers Ex-smokers Current smokers Drinking status, n (%) Non-drinkers Occasional drinkers Regular drinkers Body mass index, kg/m2 SBP, mmHg DBP, mmHg Quartile 1 (n=93) Quartile 2 (n=99) Quartile 3 (n=100) Quartile 4 (n=99) p value 4.2±0.6 46.0±3.8 4.1±0.5 47.2±4.5 4.2±0.5 47.0±4.9 4.2±0.6 47.1±4.4 0.46 0.25 28 (30.1) 9 (9.7) 56 (60.2) 28 (28.3) 10 (10.1) 61 (61.6) 17 (17.0) 8 (8.0) 75 (75.0) 28 (28.3) 9 (9.1) 62 (62.6) 0.37 12 (12.9) 38 (40.9) 43 (46.2) 24.8±2.5 122.7±10.2 76.7±8.9 8 (8.1) 45 (45.5) 46 (46.5) 23.6±2.6 120.4±10.9 76.0±8.6 13 (13.0) 41 (41.0) 46 (46.0) 22.8±2.6 118.5±11.3 73.4±9.1 15 (15.2) 37 (37.4) 47 (47.5) 21.4±2.6 119.0±10.9 72.9±9.0 0.81 <0.001 <0.05 <0.01 Data are expressed as mean±SD or n (%). SBP, systolic blood pressure; DBP, diastolic blood pressure. Table 2. Baseline Biochemical Characteristics of the Study Population Based on Serum Adiponectin Level Quartiles Characteristics Serum adiponectin level, μg/mL Mean±SD Median (IQR) log-adiponectin level Triglyceride, mg/dL log-triglyceride Cholesterol level, mg/dL TC LDL-C HDL-C HbA1c, % Quartile 1 (n=93) Quartile 2 (n=99) Quartile 3 (n=100) Quartile 4 (n=99) 3.59±0.7 3.70 (3.2–4.1) 1.27±0.2 288.63±159.2 5.37±0.7 5.29±0.5 5.30 (4.8–5.8) 1.66±0.1 191.64±159.2 5.04±0.6 7.28±0.7 7.20 (6.7–7.8) 1.98±0.1 137.64±66.3 4.82±0.5 11.18±2.5 10.60 (9.4–12.2) 2.39±0.2 132.65±277.8 4.59±0.6 <0.001 206.28±35.9 109.24±28.8 50.86±8.7 4.83±0.5 200.92±34.1 107.72±28.6 56.78±12.7 4.69±0.4 197.76±36.0 109.94±31.2 61.11±15.5 4.73±0.4 195.04±31.9 103.72±26.9 69.99±14.2 4.68±0.4 0.13 0.43 <0.001 0.07 p value <0.001 <0.001 Data are expressed as mean±SD unless otherwise noted. IQR, interquartile range; TC, total cholesterol; HDL-C, high-density lipoprotein-cholesterol; HbA1c, hemoglobin A1c. small-sample clinical or case-control studies, and thus are not sufficient to establish a cause-effect relationship. We therefore carried out a prospective study to elucidate the role of adiponectin in the development of hypertension. Methods Measurement The study subjects were employees who belonged to health insurance society A in Fukuoka Prefecture, Japan. They received annual health check-ups in 2000. All the subjects were followed up at one of their health check-ups in the next 3 years: 53 subjects in 2003, 319 in 2004, and 122 in 2005. Subjects with blood pressure ≥ 140/90 mmHg, and/or taking antihypertensive drugs (n= 88), and/or with hemoglobin A1c (HbA1c) of ≥ 6.5% (n= 15) at the time of the baseline data collection in 2000 were excluded. After these exclusions, 391 healthy men were included in this study. Baseline adiponectin levels were determined in 2006 in archived serum samples that had been stored at −80°C. All of the subjects agreed to have their serum adiponectin levels measured. Height and weight were measured to calculate body mass index (BMI = weight in kg divided by the square of height in m). The systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured once using a standard mercury sphygmomanometer with the cuff on the right arm and the subjects in a sitting position. Hypertension was defined as an SBP of ≥ 140 mmHg and/o (...truncated)