Heart Rate Elevation Precedes the Development of Metabolic Syndrome in Japanese Men: A Prospective Study

417 Hypertens Res Vol.30 (2007) No.5 p.417-426 Original Article Heart Rate Elevation Precedes the Development of Metabolic Syndrome in Japanese Men: A Prospective Study Hirofumi TOMIYAMA1), Jiko YAMADA1), Yutaka KOJI1), Minoru YAMBE1), Kohki MOTOBE1), Kazuki SHIINA1), Yoshio YAMAMOTO2), and Akira YAMASHINA1) This observational study of Japanese men without metabolic syndrome (MetS) (age: 41 ± 8 years) was conducted to clarify whether or not heart rate elevation precedes the development of full-blown MetS. MetS was defined based on two modifications of the criteria of the Japanese Expert Committee on the Diagnosis and Classification of Metabolic Syndrome. Premetabolic syndrome subjects were defined as those having one component of MetS with increased body mass index (BMI). Among the subjects without MetS (n = 1,859 when the BMI criterion was ≥ 25 and n = 2,020 when the BMI criterion was ≥ 27.5), the incidence of progression to full-blown MetS by the time of the second examination at the end of the 3-year study period was higher in the subjects with premetabolic syndrome than in those without it. The receiver-operator characteristic curve analysis and binary logistic regression analysis revealed that the odds ratio (OR) of a heart rate ≥ 69 beats/ min at the first examination for progression to full-blown MetS by the time of the second examination was significant in subjects with premetabolic syndrome (BMI ≥ 25: OR = 3.64 [1.22–10.88]; BMI ≥ 27.5: OR = 3.67 [1.28–10.55]; p < 0.05). Thus, heart rate elevation appears to precede the development of full-blown MetS in subjects with premetabolic syndrome. Heart rate seems to be a simple and useful marker for predicting the progression to full-blown MetS of middle-aged Japanese men with premetabolic syndrome. (Hypertens Res 2007; 30: 417–426) Key Words: heart rate, metabolic syndrome, sympathetic nervous system Introduction Recently, attention has been paid to metabolic syndrome (MetS), which refers to the clustering of several cardiovascular risk factors (obesity, dyslipidemia, raised blood pressure and raised plasma glucose) as a potent atherogenic state and which has been reported to be associated with poor cardiovascular outcomes (1, 2). Estimates of the prevalence of MetS indicate that this condition is now common in the general population. Some studies have demonstrated that subjects having one or two components of MetS frequently show progression to full-blown MetS (3, 4). Therefore, it would be desirable to have an appropriate method to stratify the risk of progression to full-blown MetS in these subjects. It has been suggested that genetic and environmental factors act in concert in the pathogenesis of MetS (5). Some studies have also suggested that sympathetic nervous activity may play a role in the pathogenesis of MetS (6–8). Heart rate is a marker of sympathetic activity, and several factors, such as emotions, tobacco use, alcohol consumption and atherosclerotic risk factors (hypertension, obesity, high cholesterol) are well From the 1)Second Department of Internal Medicine, Tokyo Medical University, Tokyo, Japan; and 2)Health Care Center, Kajima Corporation, Tokyo, Japan. This study was supported in part by a Grant-in-Aid from the Japanese Atherosclerosis Prevention Fund (to A.Y.). Address for Reprints: Akira Yamashina, M.D., Second Department of Internal Medicine, Tokyo Medical University, 6–7–1 Nishi-Shinjuku, Tokyo 160– 0023, Japan. E-mail: Received September 19, 2006; Accepted in revised form December 27, 2006. 418 Hypertens Res Vol. 30, No. 5 (2007) known to affect heart rate (7, 9, 10). Cross-sectional studies demonstrated heart rate elevation in subjects with MetS (11, 12). However, no study until now has evaluated whether or not elevated heart rate precedes the development of fullblown MetS. If precedence is confirmed, heart rate monitoring may be a useful approach to stratifying the risk of progression to full-blown MetS. Our recent 3-year observational cohort studies have demonstrated that arterial stiffness, as assessed by measurement of the brachial-ankle pulse wave velocity (PWV), increased with increases in the number of MetS components (13), and that increased arterial stiffness precedes the progression to hypertension in subjects with high-normal blood pressure, a MetS component (14). The instrument used for measuring brachial-ankle PWV also simultaneously measures heart rate. The present observational study was conducted in the same cohort to clarify whether heart rate elevation and/or increased brachial-ankle PWV may precede the development of fullblown MetS. Methods Design and Subjects The subjects of this observational study were Japanese male employees of a single large construction company. Their routine annual health checkups included evaluation of atherosclerotic risk factors (body mass index [BMI], serum levels of triglycerides [TG], high-density lipoprotein cholesterol [HDL] and total cholesterol [TC], fasting plasma glucose [FPG] and blood pressure). Smoking status (current smokers vs. non-smokers) and habitual alcohol intake status (zero intake, non-drinker group; 1–14 g/day, light alcohol intake group; 15–29 g/day, moderate alcohol intake group; over 30 g/day, heavy alcohol intake group) were assessed using a selfadministered questionnaire. For this study, in addition to the routine tests, brachial-ankle PWV measurements were also conducted on two occasions: at the beginning and at the end of the 3-year study period. The details of this observational study protocol are described elsewhere (15–17). The study was initiated in the year 2000. Subjects with positive atherosclerotic risk factors (TC≥ 6.22 mmol/L, FPG≥ 6.93 mmol/L and blood pressure≥ 140/90 mmHg) were managed in accordance with the guidelines of the Japan Atherosclerosis Society (18), Japan Diabetes Society (19), and Japanese Society of Hypertension (20). Subjects with these abnormalities were advised to visit their company’s health care center as a first step, and a management plan, including therapeutic lifestyle modifications, was drawn for each subject by by a team consisting of a doctor, a nurse and a nutritionist. In this protocol, while subjects with BMI≥ 25 kg/m2, HDL< 1.03 mmol/L, TG≥ 1.70 mmol/L, raised blood pressure (≥ 130/85 mmHg and < 140/90 mmHg) or raised plasma glucose (≥ 6.11 mmol/ L and < 6.93 mmol/L) were not provided with the aggressive approach for therapeutic lifestyle modifications. Instead, these subjects received a written recommendation for lifestyle modifications (weight reduction; a diet rich in fruits, vegetables and low-fat dairy products along with reduced intake of saturated and total fat; dietary sodium reduction; regular physical activity; moderation of alcohol consumption) and a recommendation for an annual follow-up (15–17). Subjects meeting any of the following criteria were considered ineligible for the present study: FPG≥ 6.93 mmol/L, age at the first examination in this ob (...truncated)