Original article
Vitamin D, parathyroid hormone and risk factors for coronary artery disease in an elderly Chinese population Wei R. Chena, Yun D. Chena, Yang Shib, Da W. Yinb, Hao Wangb and Yuan Shab Aims Low vitamin D status has been shown to be associated with coronary artery disease; most studies have involved in adults, but few have involved elderly people. We planned to research the association between vitamin D, parathyroid hormone (PTH) and coronary artery disease in elderly people. Methods A population-based study was conducted among 1245 Chinese participants, aged 60–102 years, in the spring of 2013. Serum 25-hydroxyvitamin D (25 (OH)D) was measured by chemiluminescence assay. The levels of PTH were measured by the electrochemiluminescence immunoassay (ECLIA) method. Results One thousand two hundred and forty-five participants, including 543 women (43.6%), were evaluated in 2013. The median concentrations of serum 25 (OH)D and PTH for the entire group were 16.8 ng/ml and 41.0 pg/ml, respectively. The prevalence rates of diabetes, hypertension, hyperlipidemia and coronary artery disease were significantly different across the 25 (OH)D quartiles. The prevalence rates of diabetes, hypertension, hyperlipidemia and coronary artery disease were also
significantly different across the PTH quartiles. In logistic regression analyses, serum 25 (OH)D levels were associated with risk of coronary artery disease in single and multiple regression models (P < 0.05). Serum PTH levels were also associated with the risk of coronary artery disease in single and multiple regression models (P < 0.05). Subgroup analyses stratified by sex or age yielded similar results. Conclusions Serum vitamin D and PTH levels are independently associated with risk of coronary artery disease in a Chinese elderly population. J Cardiovasc Med 2015, 16:59–68 Keywords: coronary artery disease, elderly, parathyroid hormone, vitamin D a Department of Cardiology, PLA General Hospital at Beijing and bDepartment of South-building Cardiology, PLA General Hospital at Beijing, China
Correspondence to Yun D. Chen, Department of Cardiology, PLA General Hospital at Beijing, China Tel: +86 10 55499009; fax: +86 10 55499209; e-mail: [email protected] Received 7 January 2014 Revised 22 February 2014 Accepted 22 February 2014
Introduction
Methods
Coronary artery disease (CAD) remains a major cause of morbidity and mortality in the world. Vitamin D is known to regulate calcium and phosphate metabolism.1 Recently, low vitamin D status has been shown to be associated with increased risk of developing cardiovascular disease, hypertension and obesity.2,3 Different mechanisms could be involved in these relationships, such as the regulation of blood pressure,4,5 glycemia,5 percentage body fat6 and serum lipids7 by vitamin D. Some studies have examined the relationship between vitamin D and CAD; most of them have involved in adults,8–10 but few in elderly people. Vitamin D via its receptor has essential actions on parathyroid cells, inhibiting PTH secretion, and parathyroid cell proliferation.11 Vitamin D deficiency has been recently associated with higher PTH levels, and PTH excess might be associated with increased risk of cardiovascular disease events.12,13 In the study, we planned to research the associations of serum vitamin D and serum PTH with the risk of CAD in a Chinese elderly population.
Selection of patients
1558-2027 ß 2015 Italian Federation of Cardiology
The study was carried out in Chinese PLA General Hospital in Beijing (latitude 398 540 N). As the level of 25 (OH)D differs with seasonal changes, the study was started at the beginning of January 2013 and was completed at the end of March 2013. One thousand six hundred and eleven consecutive healthy individuals aged at least 60 years were enrolled in the study. Of these 1611 participants, 42 were excluded for inadequate blood sample to test 25 (OH)D or PTH (n ¼ 15), or lack of demographic data (n ¼ 27). Patients were excluded if they were already taking vitamin D supplements (n ¼ 112). Patients with chronic renal failure (n ¼ 151), cardiac failure (n ¼ 53) or thyroid disorders (n ¼ 8) were also excluded from the study. Thus, 1245 participants were included in the present analysis. The study population was divided by age into four groups. Groups were divided as follows: Group 1, age 60–70 years, mean age 65.8 4.1; Group 2, age 71–79 years, mean age 74.3 3.7; Group 3, age 80–89 years, mean age 84.9 2.8 DOI:10.2459/JCM.0000000000000094
Copyright © Italian Federation of Cardiology. Unauthorized reproduction of this article is prohibited.
60 Journal of Cardiovascular Medicine 2015, Vol 16 No 1
and Group 4, age at least 90 years, mean age 92.2 2.1. Group 1 included 213 subjects, and Groups 2, 3 and 4 included 256, 539 and 237 subjects, respectively. The study was approved by the Association of Ethics in Beijing and the Chinese PLA General Hospital. It was performed in compliance with the Helsinki Declaration. Written informed consent for participation in the study was obtained from all participants. Physical activity
Information about the subjects’ physical activity was obtained using a questionnaire that recorded the length of time spent sleeping, eating, reading, and so forth.14 An activity coefficient was established for each subject by multiplying the time spent in each activity by established coefficients15,16 – 1 for sleeping and resting, 1.5 for very light activities (those that can be done sitting such as reading, writing or painting), 2.5 for light activities (e.g., walking), 5 for moderate activities (e.g., dancing) – and then dividing by 24 h. Data collecting
One physician administered a questionnaire to collect information on medical history, smoking habits and alcohol consumption. A trained technician performed anthropometric measurements, including body height, body weight and waist and hip circumference. CAD is defined as an established pattern of angina pectoris, a history of myocardial infarction or the presence of plaque documented by catheterization. Angiographic CAD was defined as greater than 50% of diameter stenosis in any of the major epicardial coronary arteries. The criteria used to define CAD were investigated by a trained physician. Hypertension was defined as blood pressure at least 140/90 mmHg or a history of antihypertensive drug use. Diabetes was defined as fasting blood glucose level at least 7.0 mmol/l or a history of oral hypoglycemic drug or insulin use. Hyperlipidemia was defined by at least one of the following criteria: fasting triglycerides greater than 150 mg/dl, total cholesterol greater than 200 mg/dl, low-density lipoprotein cholesterol (LDL cholesterol) greater than 130 mg/dl or the use of antihyperlipidemic drugs. Renal failure was defined as glomerular filtration rates (GFRs) < 60 ml/min per 1.73 m2. Cardiac failure diagnosis was based on medical history, clinical features and echocardiography results. Smoking was defined as partaking of at least one cigarette per day. Heavy drinking was defined as an average daily consumption of 50 ml or more of pure alcohol (roughly equivalent to four or more standard drinks per day).17 Body mass index (BMI) was defined as a ratio of the body weight in kilograms to the square of the height in meters. GFR was calculated using the CKD-EPI (chronic kidney disease epidemiology collaboration) equation as: GFR ¼ 141 min (Scr/k,1)a max (Scr/k,1)1.209 0.993Age 1.018 (if female) 1.159 (if black), where Scr is serum creatinine (mg/dl), k is 0.7 for females and 0.9 for males, a
is 0.329 for females and 0.411 for males, min indicates the minimum of Scr/k or 1 and max indicates the maximum of Scr/k or 1.18 Laboratory tests
Blood samples were acquired and analyzed in the Department of Clinical Biochemistry according to the department’s clinical standards. Blood was obtained by venipuncture after an overnight fast and placed into tubes that were protected from sunlight. Serum was separated and stored at 708C within 30 min of collection. Blood samples were analyzed within 2 h after collection. Serum 25 (OH)D measurements were performed with a chemiluminescence assay (Liaison; DiaSorin, Stillwater, Minnesota, USA; coefficient of variation (C.V.) ¼ 7.3%). We defined vitamin D deficiency as a serum 25 (OH)D level of less than 20 ng/ml and vitamin D insufficiency as a level of 20–29 ng/ml.19 PTH levels were measured by the ECLIA using Roche Elecsys PTH kits (Roche, Basel, Switzerland; C.V. ¼ 3.2%, normal values (n.v.) 15.0– 65.0 pg/ml). Plasma concentrations of calcium were measured using Synchron LX 20 system (Beckman Coulter Inc., Brea, California, USA; C.V. ¼ 1.1%, n.v. 4.4–5.2 mg/dl). The high-sensitivity C-reactive protein (hsCRP) levels were analyzed by a sandwich enzyme linked immunosorbent assay (hsCRP kit; BioCheck, Foster City, California, USA; C.V. ¼ 3.5%, n.v.
Vitamin D, parathyroid hormone and risk factors for coronary artery disease in an elderly Chinese population Wei R. Chena, Yun D. Chena, Yang Shib, Da W. Yinb, Hao Wangb and Yuan Shab Aims Low vitamin D status has been shown to be associated with coronary artery disease; most studies have involved in adults, but few have involved elderly people. We planned to research the association between vitamin D, parathyroid hormone (PTH) and coronary artery disease in elderly people. Methods A population-based study was conducted among 1245 Chinese participants, aged 60–102 years, in the spring of 2013. Serum 25-hydroxyvitamin D (25 (OH)D) was measured by chemiluminescence assay. The levels of PTH were measured by the electrochemiluminescence immunoassay (ECLIA) method. Results One thousand two hundred and forty-five participants, including 543 women (43.6%), were evaluated in 2013. The median concentrations of serum 25 (OH)D and PTH for the entire group were 16.8 ng/ml and 41.0 pg/ml, respectively. The prevalence rates of diabetes, hypertension, hyperlipidemia and coronary artery disease were significantly different across the 25 (OH)D quartiles. The prevalence rates of diabetes, hypertension, hyperlipidemia and coronary artery disease were also
significantly different across the PTH quartiles. In logistic regression analyses, serum 25 (OH)D levels were associated with risk of coronary artery disease in single and multiple regression models (P < 0.05). Serum PTH levels were also associated with the risk of coronary artery disease in single and multiple regression models (P < 0.05). Subgroup analyses stratified by sex or age yielded similar results. Conclusions Serum vitamin D and PTH levels are independently associated with risk of coronary artery disease in a Chinese elderly population. J Cardiovasc Med 2015, 16:59–68 Keywords: coronary artery disease, elderly, parathyroid hormone, vitamin D a Department of Cardiology, PLA General Hospital at Beijing and bDepartment of South-building Cardiology, PLA General Hospital at Beijing, China
Correspondence to Yun D. Chen, Department of Cardiology, PLA General Hospital at Beijing, China Tel: +86 10 55499009; fax: +86 10 55499209; e-mail: [email protected] Received 7 January 2014 Revised 22 February 2014 Accepted 22 February 2014
Introduction
Methods
Coronary artery disease (CAD) remains a major cause of morbidity and mortality in the world. Vitamin D is known to regulate calcium and phosphate metabolism.1 Recently, low vitamin D status has been shown to be associated with increased risk of developing cardiovascular disease, hypertension and obesity.2,3 Different mechanisms could be involved in these relationships, such as the regulation of blood pressure,4,5 glycemia,5 percentage body fat6 and serum lipids7 by vitamin D. Some studies have examined the relationship between vitamin D and CAD; most of them have involved in adults,8–10 but few in elderly people. Vitamin D via its receptor has essential actions on parathyroid cells, inhibiting PTH secretion, and parathyroid cell proliferation.11 Vitamin D deficiency has been recently associated with higher PTH levels, and PTH excess might be associated with increased risk of cardiovascular disease events.12,13 In the study, we planned to research the associations of serum vitamin D and serum PTH with the risk of CAD in a Chinese elderly population.
Selection of patients
1558-2027 ß 2015 Italian Federation of Cardiology
The study was carried out in Chinese PLA General Hospital in Beijing (latitude 398 540 N). As the level of 25 (OH)D differs with seasonal changes, the study was started at the beginning of January 2013 and was completed at the end of March 2013. One thousand six hundred and eleven consecutive healthy individuals aged at least 60 years were enrolled in the study. Of these 1611 participants, 42 were excluded for inadequate blood sample to test 25 (OH)D or PTH (n ¼ 15), or lack of demographic data (n ¼ 27). Patients were excluded if they were already taking vitamin D supplements (n ¼ 112). Patients with chronic renal failure (n ¼ 151), cardiac failure (n ¼ 53) or thyroid disorders (n ¼ 8) were also excluded from the study. Thus, 1245 participants were included in the present analysis. The study population was divided by age into four groups. Groups were divided as follows: Group 1, age 60–70 years, mean age 65.8 4.1; Group 2, age 71–79 years, mean age 74.3 3.7; Group 3, age 80–89 years, mean age 84.9 2.8 DOI:10.2459/JCM.0000000000000094
Copyright © Italian Federation of Cardiology. Unauthorized reproduction of this article is prohibited.
60 Journal of Cardiovascular Medicine 2015, Vol 16 No 1
and Group 4, age at least 90 years, mean age 92.2 2.1. Group 1 included 213 subjects, and Groups 2, 3 and 4 included 256, 539 and 237 subjects, respectively. The study was approved by the Association of Ethics in Beijing and the Chinese PLA General Hospital. It was performed in compliance with the Helsinki Declaration. Written informed consent for participation in the study was obtained from all participants. Physical activity
Information about the subjects’ physical activity was obtained using a questionnaire that recorded the length of time spent sleeping, eating, reading, and so forth.14 An activity coefficient was established for each subject by multiplying the time spent in each activity by established coefficients15,16 – 1 for sleeping and resting, 1.5 for very light activities (those that can be done sitting such as reading, writing or painting), 2.5 for light activities (e.g., walking), 5 for moderate activities (e.g., dancing) – and then dividing by 24 h. Data collecting
One physician administered a questionnaire to collect information on medical history, smoking habits and alcohol consumption. A trained technician performed anthropometric measurements, including body height, body weight and waist and hip circumference. CAD is defined as an established pattern of angina pectoris, a history of myocardial infarction or the presence of plaque documented by catheterization. Angiographic CAD was defined as greater than 50% of diameter stenosis in any of the major epicardial coronary arteries. The criteria used to define CAD were investigated by a trained physician. Hypertension was defined as blood pressure at least 140/90 mmHg or a history of antihypertensive drug use. Diabetes was defined as fasting blood glucose level at least 7.0 mmol/l or a history of oral hypoglycemic drug or insulin use. Hyperlipidemia was defined by at least one of the following criteria: fasting triglycerides greater than 150 mg/dl, total cholesterol greater than 200 mg/dl, low-density lipoprotein cholesterol (LDL cholesterol) greater than 130 mg/dl or the use of antihyperlipidemic drugs. Renal failure was defined as glomerular filtration rates (GFRs) < 60 ml/min per 1.73 m2. Cardiac failure diagnosis was based on medical history, clinical features and echocardiography results. Smoking was defined as partaking of at least one cigarette per day. Heavy drinking was defined as an average daily consumption of 50 ml or more of pure alcohol (roughly equivalent to four or more standard drinks per day).17 Body mass index (BMI) was defined as a ratio of the body weight in kilograms to the square of the height in meters. GFR was calculated using the CKD-EPI (chronic kidney disease epidemiology collaboration) equation as: GFR ¼ 141 min (Scr/k,1)a max (Scr/k,1)1.209 0.993Age 1.018 (if female) 1.159 (if black), where Scr is serum creatinine (mg/dl), k is 0.7 for females and 0.9 for males, a
is 0.329 for females and 0.411 for males, min indicates the minimum of Scr/k or 1 and max indicates the maximum of Scr/k or 1.18 Laboratory tests
Blood samples were acquired and analyzed in the Department of Clinical Biochemistry according to the department’s clinical standards. Blood was obtained by venipuncture after an overnight fast and placed into tubes that were protected from sunlight. Serum was separated and stored at 708C within 30 min of collection. Blood samples were analyzed within 2 h after collection. Serum 25 (OH)D measurements were performed with a chemiluminescence assay (Liaison; DiaSorin, Stillwater, Minnesota, USA; coefficient of variation (C.V.) ¼ 7.3%). We defined vitamin D deficiency as a serum 25 (OH)D level of less than 20 ng/ml and vitamin D insufficiency as a level of 20–29 ng/ml.19 PTH levels were measured by the ECLIA using Roche Elecsys PTH kits (Roche, Basel, Switzerland; C.V. ¼ 3.2%, normal values (n.v.) 15.0– 65.0 pg/ml). Plasma concentrations of calcium were measured using Synchron LX 20 system (Beckman Coulter Inc., Brea, California, USA; C.V. ¼ 1.1%, n.v. 4.4–5.2 mg/dl). The high-sensitivity C-reactive protein (hsCRP) levels were analyzed by a sandwich enzyme linked immunosorbent assay (hsCRP kit; BioCheck, Foster City, California, USA; C.V. ¼ 3.5%, n.v.
