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Association of heart rate with albuminuria in a general adult population: the 2011 Korea National Health and Nutrition Examination Survey H. S. Choi,1 J. W. Hong,2 J. H. Lee,3 J. H. Noh2 and D. J. Kim2 1 Division of Endocrinology and Metabolism, Department of Internal Medicine, Dongguk University Ilsan Hospital, 2Department of Internal Medicine, Ilsan-Paik Hospital, College of Medicine, Inje University and 3Division of Endocrinology and Metabolism, Department of Internal Medicine, Myongji
Hospital, Koyang, Gyeonggi-do, South Korea
Key words albuminuria, microalbuminuria, heart rate, cardiovascular disease. Correspondence Dong-Jun Kim, Department of Internal Medicine, Ilsan-Paik Hospital, 2240 Daehwa-dong, Ilsanseoku, Koyang City, Gyonggi-do 411-706, South Korea. Email: [email protected] Received 5 August 2014; accepted 14 December 2014. doi:10.1111/imj.12672
Abstract Background: Albuminuria is associated with increased risk of multiple adverse health outcomes, such as progressive renal failure, cardiovascular disease and death. However, in the general population, it is uncertain whether albuminuria is associated with elevated heart rate, which is an independent and powerful risk factor for cardiovascular disease. Aim: To investigate whether an elevated heart rate is an independent factor associated with albuminuria in the general adult population of Korea. Methods: A cross-sectional analysis was carried out on 5198 Korean adults aged 19 years or older who participated in the fifth (2011) Korea National Health and Nutrition Examination Survey (KNHANES V-2). Results: The prevalence of albuminuria showed an increasing trend throughout the whole range of heart rate, even after adjusting for confounders (P = 0.002). The increment was most profound at the heart rate of 70–75 and >76 beats per minute (b.p.m.; P = 0.011). In multiple logistic regression analysis, age (P < 0.001), hypertension (P < 0.001), diabetes (P < 0.001), hypertriglyceridaemia (P = 0.025), estimated glomerular filtration rate (P = 0.028) and heart rate (P = 0.023) were independently associated with the presence of albuminuria in Korean adults. Compared with participants with heart rate ≤64 b.p.m., the odds ratio (95% CI) for albuminuria was 1.50 (1.15–1.96) for those with heart rate ≥76 b.p.m. Conclusions: The prevalence of albuminuria is independently associated with heart rate in the general adult population of Korea.
Introduction Albuminuria is a common health condition. Its prevalence increases with age. In the United States, the prevalence of micro- and macroalbuminuria in the adult population is estimated to be 8.2% and 1.3% respectively.1 As we recently reported, the prevalence of microand macro-albuminuria in Korean adults is 5.2% and 1.0% respectively.2 Also, in other countries, microalbuminuria is very common in the general population with a respective prevalence of 4.6%, 6.0% and 7% in Japan,
Funding: This work was supported by the Dongguk University Research Fund 2011. Conflict of interest: None.
Australia and Europe, although there exist some discrepancies due to differences in the population analysed, diagnostic criteria or method of measurement.3–5 In addition, the prevalence of microalbuminuria rises to 16% and 29% in individuals with hypertension and diabetes respectively.6,7 With regards to clinical significance, the presence of albuminuria has been associated with increased risk of multiple adverse health outcomes, such as progressive renal failure, cardiovascular disease or death, not only in diabetic or hypertensive patients, but also in non-diabetic and non-hypertensive subjects.8–13 More recent studies have shown that the risk of adverse health outcomes is increased at even very low levels of albuminuria. A study showed that for every 3.5 mg/g of creatinine (Cr) increase in albumin-creatinine ratio (ACR) the risk of © 2014 Royal Australasian College of Physicians
428
Heart rate and albuminuria
major cardiovascular events increased by 5.9%.14 Hillege et al. also reported that a twofold increase in urinary albumin concentration was associated with a 12% increased risk for non-cardiovascular mortality.13 Therapeutic reduction of albuminuria with pharmacological interventions using angiotensin-converting enzyme inhibitors or angiotension II-receptor blockers has been consistently associated with reduced progression of renal disease or improved cardiovascular outcomes.15–18 Accordingly, albuminuria is now recognised as a risk predictor and a treatment target in individuals with increased risk for renal or cardiovascular diseases. Associated factors for albuminuria include older age, hypertension, hypertriglyceridaemia, impaired fasting glucose and diabetes.19–21 Also, in Korean adults, older age, female sex, hypertension, serum triglyceride and diabetes are independently associated with albuminuria.2 An elevated heart rate is closely associated with an adverse cardiovascular outcome in hypertensive and diabetic individuals, and also the general population.22–24 An elevated heart rate can promote atherosclerosis by enhancing the magnitude and frequency of the tensile stress imposed on the arterial wall and by increasing systolic flow-induced shear stress.25 It can also be speculated that the number of pulse waves caused by a high heart rate might also contribute to glomerular damage that can lead to transvascular leakage of albumin in the kidney. We hypothesised that elevated heart rate might be a predictor for albuminuria even in a general population. To test this hypothesis, we performed a cross-sectional analysis to investigate the association between heart rate and albuminuria. Analyses were performed using data from participants in the fifth Korea National Health and Nutrition Examination Survey (KNHANES V-2) from 2011.
Methods Study population and data collection This study is based on the data from KNHANES V-2, a cross-sectional and nationally representative survey conducted by the Korean Center for Disease Control for Health Statistics. KNHANES has been conducted periodically since 1998 to assess the health and nutritional status of the civilian non-institutionalised population of Korea. Participants were chosen using proportional allocationsystemic sampling with multistage stratification. In KNHANES V-2, 3840 households were selected. A standardised interview was conducted in the homes of the participants to collect information on demographic variables, family history, medical history and a variety of
other health-related variables. The health interview included well-established questions to determine the demographic and socioeconomic characteristics of the subjects, including questions on age, education level, occupation, income, marital status, smoking habit, alcohol consumption, exercise, previous and current diseases and family disease history. Smoking status was divided into three categories: current smoker, ex-smoker and nonsmoker. Subjects were questioned about whether they exercised with an intensity that left them with slight difficulty in breathing and sweating. Subjects who exercised regularly at a moderate intensity were asked about the frequency at which they exercised per week and the length of time per exercise session. Regular exercise was defined exercising five or more times per week. Alcohol consumption was assessed by questioning the subjects about their drinking behaviour during the month before the interview. Heavy alcohol drinking was categorised as drinking four or more times per week. Hypertension was defined as systolic blood pressure (BP) ≥ 140 mmHg, diastolic BP ≥ 90 mmHg or use of antihypertensive medications irrespective of blood pressure. Diabetes was defined as fasting plasma glucose ≥7.0 mmol/L, current anti-diabetes medication or a previous diagnosis of diabetes by a doctor. Obesity was defined as body mass index (BMI) ≥ 25 kg/m2 according to the Asia-Pacific obesity classification.26 Height and weight were obtained using standardised techniques and equipment. Height was measured to the nearest 0.1 cm using a portable stadiometer (Seriter, Bismarck, ND). Weight was measured to the nearest 0.1 kg using a Giant-150N calibrated balance-beam scale (Hana, Seoul, Korea). BMI was calculated by dividing weight by the square of height (kg/m2). Systolic and diastolic BP was measured by standard methods using a sphygmomanometer with the patient in the sitting position. Three measurements were made for all subjects at 5-min intervals; the average of the second and third measurements was used in the analysis. Heart rate per minute was determined by counting the number of beats on the subject’s wrist for 15 s and multiplying this number by 4 to yield beats per minute (b.p.m.). The median (interquartile) value of heart rate in our participants was 68 (range, 64–76) b.p.m.. Taking into account the distribution of heart rate, we classified our participants into four groups: heart rate ≤64 (n = 2009), 65–69 (n = 873), 70–75 (n = 926) and ≥76 (n = 1390) b.p.m.. This study was approved by the institutional review board of Ilsan Paik Hospital, Republic of Korea (IB-31402-006). After approval of the study proposal, the KNHANES dataset was made available at the request of the investigator. As the dataset did not include any personal information and, since participant consent had
© 2014 Royal Australasian College of Physicians
429
Choi et al.
already been given for the KNHANES, our study was exempt from participant consent.
Laboratory methods Blood samples were collected in the morning after fasting for at least 8 h. Fasting plasma glucose (FPG), total cholesterol, triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) levels were measured by a model 7600 automatic analyser 7600 (Hitachi, Tokyo, Japan). Urine albumin and creatinine concentrations were measured in the same laboratory during all surveys. Serum and urinary concentrations of creatinine were measured by a colorimetric method using the aforementioned automatic analyser. The inter-assay coefficient of variation for serum creatinine was
Association of heart rate with albuminuria in a general adult population: the 2011 Korea National Health and Nutrition Examination Survey H. S. Choi,1 J. W. Hong,2 J. H. Lee,3 J. H. Noh2 and D. J. Kim2 1 Division of Endocrinology and Metabolism, Department of Internal Medicine, Dongguk University Ilsan Hospital, 2Department of Internal Medicine, Ilsan-Paik Hospital, College of Medicine, Inje University and 3Division of Endocrinology and Metabolism, Department of Internal Medicine, Myongji
Hospital, Koyang, Gyeonggi-do, South Korea
Key words albuminuria, microalbuminuria, heart rate, cardiovascular disease. Correspondence Dong-Jun Kim, Department of Internal Medicine, Ilsan-Paik Hospital, 2240 Daehwa-dong, Ilsanseoku, Koyang City, Gyonggi-do 411-706, South Korea. Email: [email protected] Received 5 August 2014; accepted 14 December 2014. doi:10.1111/imj.12672
Abstract Background: Albuminuria is associated with increased risk of multiple adverse health outcomes, such as progressive renal failure, cardiovascular disease and death. However, in the general population, it is uncertain whether albuminuria is associated with elevated heart rate, which is an independent and powerful risk factor for cardiovascular disease. Aim: To investigate whether an elevated heart rate is an independent factor associated with albuminuria in the general adult population of Korea. Methods: A cross-sectional analysis was carried out on 5198 Korean adults aged 19 years or older who participated in the fifth (2011) Korea National Health and Nutrition Examination Survey (KNHANES V-2). Results: The prevalence of albuminuria showed an increasing trend throughout the whole range of heart rate, even after adjusting for confounders (P = 0.002). The increment was most profound at the heart rate of 70–75 and >76 beats per minute (b.p.m.; P = 0.011). In multiple logistic regression analysis, age (P < 0.001), hypertension (P < 0.001), diabetes (P < 0.001), hypertriglyceridaemia (P = 0.025), estimated glomerular filtration rate (P = 0.028) and heart rate (P = 0.023) were independently associated with the presence of albuminuria in Korean adults. Compared with participants with heart rate ≤64 b.p.m., the odds ratio (95% CI) for albuminuria was 1.50 (1.15–1.96) for those with heart rate ≥76 b.p.m. Conclusions: The prevalence of albuminuria is independently associated with heart rate in the general adult population of Korea.
Introduction Albuminuria is a common health condition. Its prevalence increases with age. In the United States, the prevalence of micro- and macroalbuminuria in the adult population is estimated to be 8.2% and 1.3% respectively.1 As we recently reported, the prevalence of microand macro-albuminuria in Korean adults is 5.2% and 1.0% respectively.2 Also, in other countries, microalbuminuria is very common in the general population with a respective prevalence of 4.6%, 6.0% and 7% in Japan,
Funding: This work was supported by the Dongguk University Research Fund 2011. Conflict of interest: None.
Australia and Europe, although there exist some discrepancies due to differences in the population analysed, diagnostic criteria or method of measurement.3–5 In addition, the prevalence of microalbuminuria rises to 16% and 29% in individuals with hypertension and diabetes respectively.6,7 With regards to clinical significance, the presence of albuminuria has been associated with increased risk of multiple adverse health outcomes, such as progressive renal failure, cardiovascular disease or death, not only in diabetic or hypertensive patients, but also in non-diabetic and non-hypertensive subjects.8–13 More recent studies have shown that the risk of adverse health outcomes is increased at even very low levels of albuminuria. A study showed that for every 3.5 mg/g of creatinine (Cr) increase in albumin-creatinine ratio (ACR) the risk of © 2014 Royal Australasian College of Physicians
428
Heart rate and albuminuria
major cardiovascular events increased by 5.9%.14 Hillege et al. also reported that a twofold increase in urinary albumin concentration was associated with a 12% increased risk for non-cardiovascular mortality.13 Therapeutic reduction of albuminuria with pharmacological interventions using angiotensin-converting enzyme inhibitors or angiotension II-receptor blockers has been consistently associated with reduced progression of renal disease or improved cardiovascular outcomes.15–18 Accordingly, albuminuria is now recognised as a risk predictor and a treatment target in individuals with increased risk for renal or cardiovascular diseases. Associated factors for albuminuria include older age, hypertension, hypertriglyceridaemia, impaired fasting glucose and diabetes.19–21 Also, in Korean adults, older age, female sex, hypertension, serum triglyceride and diabetes are independently associated with albuminuria.2 An elevated heart rate is closely associated with an adverse cardiovascular outcome in hypertensive and diabetic individuals, and also the general population.22–24 An elevated heart rate can promote atherosclerosis by enhancing the magnitude and frequency of the tensile stress imposed on the arterial wall and by increasing systolic flow-induced shear stress.25 It can also be speculated that the number of pulse waves caused by a high heart rate might also contribute to glomerular damage that can lead to transvascular leakage of albumin in the kidney. We hypothesised that elevated heart rate might be a predictor for albuminuria even in a general population. To test this hypothesis, we performed a cross-sectional analysis to investigate the association between heart rate and albuminuria. Analyses were performed using data from participants in the fifth Korea National Health and Nutrition Examination Survey (KNHANES V-2) from 2011.
Methods Study population and data collection This study is based on the data from KNHANES V-2, a cross-sectional and nationally representative survey conducted by the Korean Center for Disease Control for Health Statistics. KNHANES has been conducted periodically since 1998 to assess the health and nutritional status of the civilian non-institutionalised population of Korea. Participants were chosen using proportional allocationsystemic sampling with multistage stratification. In KNHANES V-2, 3840 households were selected. A standardised interview was conducted in the homes of the participants to collect information on demographic variables, family history, medical history and a variety of
other health-related variables. The health interview included well-established questions to determine the demographic and socioeconomic characteristics of the subjects, including questions on age, education level, occupation, income, marital status, smoking habit, alcohol consumption, exercise, previous and current diseases and family disease history. Smoking status was divided into three categories: current smoker, ex-smoker and nonsmoker. Subjects were questioned about whether they exercised with an intensity that left them with slight difficulty in breathing and sweating. Subjects who exercised regularly at a moderate intensity were asked about the frequency at which they exercised per week and the length of time per exercise session. Regular exercise was defined exercising five or more times per week. Alcohol consumption was assessed by questioning the subjects about their drinking behaviour during the month before the interview. Heavy alcohol drinking was categorised as drinking four or more times per week. Hypertension was defined as systolic blood pressure (BP) ≥ 140 mmHg, diastolic BP ≥ 90 mmHg or use of antihypertensive medications irrespective of blood pressure. Diabetes was defined as fasting plasma glucose ≥7.0 mmol/L, current anti-diabetes medication or a previous diagnosis of diabetes by a doctor. Obesity was defined as body mass index (BMI) ≥ 25 kg/m2 according to the Asia-Pacific obesity classification.26 Height and weight were obtained using standardised techniques and equipment. Height was measured to the nearest 0.1 cm using a portable stadiometer (Seriter, Bismarck, ND). Weight was measured to the nearest 0.1 kg using a Giant-150N calibrated balance-beam scale (Hana, Seoul, Korea). BMI was calculated by dividing weight by the square of height (kg/m2). Systolic and diastolic BP was measured by standard methods using a sphygmomanometer with the patient in the sitting position. Three measurements were made for all subjects at 5-min intervals; the average of the second and third measurements was used in the analysis. Heart rate per minute was determined by counting the number of beats on the subject’s wrist for 15 s and multiplying this number by 4 to yield beats per minute (b.p.m.). The median (interquartile) value of heart rate in our participants was 68 (range, 64–76) b.p.m.. Taking into account the distribution of heart rate, we classified our participants into four groups: heart rate ≤64 (n = 2009), 65–69 (n = 873), 70–75 (n = 926) and ≥76 (n = 1390) b.p.m.. This study was approved by the institutional review board of Ilsan Paik Hospital, Republic of Korea (IB-31402-006). After approval of the study proposal, the KNHANES dataset was made available at the request of the investigator. As the dataset did not include any personal information and, since participant consent had
© 2014 Royal Australasian College of Physicians
429
Choi et al.
already been given for the KNHANES, our study was exempt from participant consent.
Laboratory methods Blood samples were collected in the morning after fasting for at least 8 h. Fasting plasma glucose (FPG), total cholesterol, triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) levels were measured by a model 7600 automatic analyser 7600 (Hitachi, Tokyo, Japan). Urine albumin and creatinine concentrations were measured in the same laboratory during all surveys. Serum and urinary concentrations of creatinine were measured by a colorimetric method using the aforementioned automatic analyser. The inter-assay coefficient of variation for serum creatinine was
