Clinical Hemorheology and Microcirculation 60 (2015) 327–334 DOI 10.3233/CH-141887 IOS Press
327
Association of metabolic syndrome and its components with hyperuricemia in a Mediterranean population Amparo Vay´aa,∗ , Leonor Riveraa , Antonio Hern´andez-Mijaresb , Daniel Bautistac , Eva Sol´ab , Marco Romagnolid,e , Rafael Alise,f and Bego˜na Laiza a
Hemorheology and Haemostasis Unit, Service of Clinical Pathology, La Fe University Hospital, Valencia, Spain b Endocrinology Service, Dr. Peset University Hospital, Valencia, Spain c Epidemiology Service, Dr. Peset University Hospital, Valencia, Spain d Department of Physical Education and Sports, Catholic University of Valencia “San Vicente M´artir”, Valencia, Spain e Research Universitary Institute “Dr. Vi˜na Giner”, Molecular and Mitochondrial Medicine, Catholic University of Valencia “San Vicente Mártir”, Valencia, Spain f Faculty of Medicine, Catholic University of Valencia “San Vicente Mártir”, Valencia, Spain
Abstract. Several studies have found an association between hyperuricemia and metabolic syndrome (MS), although there are discrepancies as to which MS components play a pivotal role in this association. We aimed to investigate the association between serum uric acid (SUA) levels and MS in a Mediterranean population (eastern Spain). We performed a case-control study of 71 patients with MS and 122 healthy controls. MS was defined according to the revised National Cholesterol Education Program Adult Treatment Panel III modified criteria. Hyperuricemia was defined as SUA levels >6.55 mg/dL. We determined biochemical, lipidic and inflammatory parameters along with uric acid. Patients with MS showed a higher risk of hyperuricemia than those without MS (OR: 2.87 95%CI: 1.48–5.55; p = 0.002). In turn, the unadjusted logistic regression analysis showed that hyperuricemia is associated with a higher risk of presenting all the MS components, except hypertension; i.e., hypertriglyceridemia, low HDL-cholesterol, abdominal obesity and glucose intolerance were predictors for hyperuricemia (OR: 3.15, 95%CI: 1.61–6.15, p = 0.001; OR: 4.07, 95%CI: 1.77–9.33, p = 0.001; OR: 2.81, 95%CI: 1.41–5.58, p = 0.003 and OR: 2.82, 95%CI: 1.46–5.45, p = 0.002 respectively). The adjusted logistic regression analysis revealed that only low HDL-cholesterol and glucose intolerance were independent predictors for hyperuricemia (OR: 2.71, 95%CI 1.06–6.97, p = 0.038; OR: 2.14, 95%CI 1.01–4.56, p = 0.049, respectively). In our geographical area, the patients with MS showed a nearly 3-fold risk of hyperuricemia than those without. Among all the MS components, low-HDL-cholesterol and high glucose independently increased more than twice the risk of hyperuricemia, and are the pivotal components involved in hyperuricemia. Keywords: Hyperuricemia, metabolic syndrome, mediterranean population, low HDL-cholesterol, high glucose levels
1. Introduction Metabolic syndrome (MS) is a cluster of interrelated metabolic abnormalities that includes glucose intolerance, insulin resistance, abdominal obesity, dyslipidemia and hypertension [1, 13]. It is wellknown that individuals with MS are at increased risk of cardiovascular disease and type 2 diabetes [12]. ∗ Corresponding author: Amparo Vay´a, MD, PhD, Hemorheology and Hemostasis Unit, Service of Clinical Pathology, La Fe University Hospital, Avda. de Campanar, 21, 46009, Valencia, Spain. Tel./Fax: +34 963862714; E-mail: vaya [email protected].
1386-0291/15/$35.00 © 2015 – IOS Press and the authors. All rights reserved
328
A. Vay´a et al. / Hyperuricemia and metabolic syndrome
Several studies have shown that the traditional risk factors defined in MS cannot explain all the cardiovascular events observed in these individuals. Therefore, other factors including inflammatory markers, abnormalities of coagulation and hyperuricemia have been suggested to be considered to evaluate the risk of cardiovascular diseases in these patients. Moreover, several authors have suggested that serum uric acid (SUA) levels should be included in the definition of MS [3, 24, 30] as increased SUA levels are independently associated with a higher risk of cardiovascular mortality [6, 10]. The association of MS and its several components, i.e., hypertension, glucose intolerance, low HDLcholesterol, hypertriglyceridemia and abdominal obesity with hyperuricemia, varies in the several studies analysed [4, 7, 8, 16–18, 27, 31]. This fact may be attributed to the different criteria used for the definition of MS [1, 2, 13], and also to the different ethnicities in which the studies have been carried out. In Spain, two studies on this topic have been performed [25, 26]. The regions in these two studies are not located on the coast, where lifestyle and dietary habits are not similar. Therefore, differences exist in MS prevalence [19]. In our geographical area (eastern Spain on the coast), no studies have been conducted in this respect. The aim of the present study was to analyze the association of hyperuricemia and MS and its several components in a Mediterranean population by means of a case-control study. 2. Materials and methods 2.1. Subjects Seventy-one consecutive outpatients with MS (49 males, 22 females), aged 50 ± 11 years, attending the Endocrinology Service at the Dr. Peset University Hospital (Valencia, Spain) between January 2011 and December 2011 constituted the case group. Exclusion criteria were hepatic, renal, infectious, inflammatory or malignant diseases, and previous thrombotic events. Those patients under treatment with hypuricemic drugs were also excluded. One hundred and twenty-two volunteer blood donors from the Valencian Community Transfusion Center (73 males, 49 females), aged 49 ± 10 years, constituted the control group, in whom MS was ruled out when they presented none, one or two features of MS. Controls and patients were from the same geographical area (eastern Spain) and they were all Caucasians. The inclusion of patients and controls in the study was performed simultaneously, as were sampling and analytical testing. An informed consent from all the participants and approval from our hospital’s Ethics Committee were obtained. The work complies with the principles of the Declaration of Helsinki and was performed in accordance with the ethical guidelines for Clinical Hemorheology and Microcirculation. MS was defined according to the NCEP ATPIII criteria modified by Grundy et al. [13] as having three or more risk factors, including the following: abdominal obesity (waist circumference ≥102 cm for men and ≥88 cm for women); triglycerides ≥150 mg/dL or drug treatment for elevated triglycerides; HDLcholesterol6.55 mg/dL). The cut-off point for defining hyperuricemia was obtained from the normal values of the control group, plus one standard deviation (SD). Data are expressed as means ± one SD. For statistical inference, a bilateral p-value of < 0.05 was considered statistically significant. All the analyses were calculated using the Statistical Package for Social Sciences (SPSS, version 11) for Windows. 3. Results Table 1 shows the anthropometric, lipidic and inflammatory characteristics for MS patients and controls. When compared with controls, MS patients presented higher BMI, waist circumference, uric acid, glucose, triglycerides, insulin, CRP levels, leucocytes, neutrophils (p < 0.001, respectively), HOMA (p < 0.010) and lower HDL-Cholesterol (p < 0.001). The Pearson bivariate correlation between SUA and the several analyzed parameters indicated that SUA correlated only with waist (r = 0.242, p < 0.05), creatinine (r = 0.469, p < 0.01) and triglycerides (r = 0.291, p < 0.05). Table 2 shows the prevalence of MS and its individual components in patients with SUA >6.55 mg/dL and those with SUA 6.55 mg/dL (p = 0.001, p = 0.001, p = 0.001, p = 0.003 and p = 0.002, respectively).
330
A. Vay´a et al. / Hyperuricemia and metabolic syndrome Table 1 Anthropometric, lipidic and inflammatory characteristics for MS patients and controls
Age (years) Gender (male/female) BMI (kg/m2 ) Waist (cm) Glucose (mg/dL) Serum Uric acid (mg/dL) Creatinine (mg/dL) HDL-Cholesterol (mg/dL) Triglycerides (mg/dL) CRP (mg/L) Fibrinogen (mg/dL) Leucocytes (106 /L) Neutrophils (103 /L) Insulin (U/mL) HOMA
Metabolic syndrome n = 71
Control n = 122
p
41 ± 12 49/22 32.9 ± 4.6 110.2 ± 11.4 120 ± 34 6.2 ± 1.5 0.88 ± 0.18 48 ± 12 176 ± 73 5.56 ± 8.64 367 ± 75 7.22 ± 1.68 4.17 ± 1.37 18.59 ± 12.09 9.18 ± 25.35
45 ± 11 73/49 26.2 ± 3.8 91.6 ± 10.8 95 ± 14 5.2 ± 1.3 0.86 ± 0.16 59 ± 14 99 ± 41 1.75 ± 1.98 312 ± 55 6.03 ± 1.68 3.32 ± 1.21 7.25 ± 3.69 1.82 ± 1.02
0.060 0.202
327
Association of metabolic syndrome and its components with hyperuricemia in a Mediterranean population Amparo Vay´aa,∗ , Leonor Riveraa , Antonio Hern´andez-Mijaresb , Daniel Bautistac , Eva Sol´ab , Marco Romagnolid,e , Rafael Alise,f and Bego˜na Laiza a
Hemorheology and Haemostasis Unit, Service of Clinical Pathology, La Fe University Hospital, Valencia, Spain b Endocrinology Service, Dr. Peset University Hospital, Valencia, Spain c Epidemiology Service, Dr. Peset University Hospital, Valencia, Spain d Department of Physical Education and Sports, Catholic University of Valencia “San Vicente M´artir”, Valencia, Spain e Research Universitary Institute “Dr. Vi˜na Giner”, Molecular and Mitochondrial Medicine, Catholic University of Valencia “San Vicente Mártir”, Valencia, Spain f Faculty of Medicine, Catholic University of Valencia “San Vicente Mártir”, Valencia, Spain
Abstract. Several studies have found an association between hyperuricemia and metabolic syndrome (MS), although there are discrepancies as to which MS components play a pivotal role in this association. We aimed to investigate the association between serum uric acid (SUA) levels and MS in a Mediterranean population (eastern Spain). We performed a case-control study of 71 patients with MS and 122 healthy controls. MS was defined according to the revised National Cholesterol Education Program Adult Treatment Panel III modified criteria. Hyperuricemia was defined as SUA levels >6.55 mg/dL. We determined biochemical, lipidic and inflammatory parameters along with uric acid. Patients with MS showed a higher risk of hyperuricemia than those without MS (OR: 2.87 95%CI: 1.48–5.55; p = 0.002). In turn, the unadjusted logistic regression analysis showed that hyperuricemia is associated with a higher risk of presenting all the MS components, except hypertension; i.e., hypertriglyceridemia, low HDL-cholesterol, abdominal obesity and glucose intolerance were predictors for hyperuricemia (OR: 3.15, 95%CI: 1.61–6.15, p = 0.001; OR: 4.07, 95%CI: 1.77–9.33, p = 0.001; OR: 2.81, 95%CI: 1.41–5.58, p = 0.003 and OR: 2.82, 95%CI: 1.46–5.45, p = 0.002 respectively). The adjusted logistic regression analysis revealed that only low HDL-cholesterol and glucose intolerance were independent predictors for hyperuricemia (OR: 2.71, 95%CI 1.06–6.97, p = 0.038; OR: 2.14, 95%CI 1.01–4.56, p = 0.049, respectively). In our geographical area, the patients with MS showed a nearly 3-fold risk of hyperuricemia than those without. Among all the MS components, low-HDL-cholesterol and high glucose independently increased more than twice the risk of hyperuricemia, and are the pivotal components involved in hyperuricemia. Keywords: Hyperuricemia, metabolic syndrome, mediterranean population, low HDL-cholesterol, high glucose levels
1. Introduction Metabolic syndrome (MS) is a cluster of interrelated metabolic abnormalities that includes glucose intolerance, insulin resistance, abdominal obesity, dyslipidemia and hypertension [1, 13]. It is wellknown that individuals with MS are at increased risk of cardiovascular disease and type 2 diabetes [12]. ∗ Corresponding author: Amparo Vay´a, MD, PhD, Hemorheology and Hemostasis Unit, Service of Clinical Pathology, La Fe University Hospital, Avda. de Campanar, 21, 46009, Valencia, Spain. Tel./Fax: +34 963862714; E-mail: vaya [email protected].
1386-0291/15/$35.00 © 2015 – IOS Press and the authors. All rights reserved
328
A. Vay´a et al. / Hyperuricemia and metabolic syndrome
Several studies have shown that the traditional risk factors defined in MS cannot explain all the cardiovascular events observed in these individuals. Therefore, other factors including inflammatory markers, abnormalities of coagulation and hyperuricemia have been suggested to be considered to evaluate the risk of cardiovascular diseases in these patients. Moreover, several authors have suggested that serum uric acid (SUA) levels should be included in the definition of MS [3, 24, 30] as increased SUA levels are independently associated with a higher risk of cardiovascular mortality [6, 10]. The association of MS and its several components, i.e., hypertension, glucose intolerance, low HDLcholesterol, hypertriglyceridemia and abdominal obesity with hyperuricemia, varies in the several studies analysed [4, 7, 8, 16–18, 27, 31]. This fact may be attributed to the different criteria used for the definition of MS [1, 2, 13], and also to the different ethnicities in which the studies have been carried out. In Spain, two studies on this topic have been performed [25, 26]. The regions in these two studies are not located on the coast, where lifestyle and dietary habits are not similar. Therefore, differences exist in MS prevalence [19]. In our geographical area (eastern Spain on the coast), no studies have been conducted in this respect. The aim of the present study was to analyze the association of hyperuricemia and MS and its several components in a Mediterranean population by means of a case-control study. 2. Materials and methods 2.1. Subjects Seventy-one consecutive outpatients with MS (49 males, 22 females), aged 50 ± 11 years, attending the Endocrinology Service at the Dr. Peset University Hospital (Valencia, Spain) between January 2011 and December 2011 constituted the case group. Exclusion criteria were hepatic, renal, infectious, inflammatory or malignant diseases, and previous thrombotic events. Those patients under treatment with hypuricemic drugs were also excluded. One hundred and twenty-two volunteer blood donors from the Valencian Community Transfusion Center (73 males, 49 females), aged 49 ± 10 years, constituted the control group, in whom MS was ruled out when they presented none, one or two features of MS. Controls and patients were from the same geographical area (eastern Spain) and they were all Caucasians. The inclusion of patients and controls in the study was performed simultaneously, as were sampling and analytical testing. An informed consent from all the participants and approval from our hospital’s Ethics Committee were obtained. The work complies with the principles of the Declaration of Helsinki and was performed in accordance with the ethical guidelines for Clinical Hemorheology and Microcirculation. MS was defined according to the NCEP ATPIII criteria modified by Grundy et al. [13] as having three or more risk factors, including the following: abdominal obesity (waist circumference ≥102 cm for men and ≥88 cm for women); triglycerides ≥150 mg/dL or drug treatment for elevated triglycerides; HDLcholesterol6.55 mg/dL). The cut-off point for defining hyperuricemia was obtained from the normal values of the control group, plus one standard deviation (SD). Data are expressed as means ± one SD. For statistical inference, a bilateral p-value of < 0.05 was considered statistically significant. All the analyses were calculated using the Statistical Package for Social Sciences (SPSS, version 11) for Windows. 3. Results Table 1 shows the anthropometric, lipidic and inflammatory characteristics for MS patients and controls. When compared with controls, MS patients presented higher BMI, waist circumference, uric acid, glucose, triglycerides, insulin, CRP levels, leucocytes, neutrophils (p < 0.001, respectively), HOMA (p < 0.010) and lower HDL-Cholesterol (p < 0.001). The Pearson bivariate correlation between SUA and the several analyzed parameters indicated that SUA correlated only with waist (r = 0.242, p < 0.05), creatinine (r = 0.469, p < 0.01) and triglycerides (r = 0.291, p < 0.05). Table 2 shows the prevalence of MS and its individual components in patients with SUA >6.55 mg/dL and those with SUA 6.55 mg/dL (p = 0.001, p = 0.001, p = 0.001, p = 0.003 and p = 0.002, respectively).
330
A. Vay´a et al. / Hyperuricemia and metabolic syndrome Table 1 Anthropometric, lipidic and inflammatory characteristics for MS patients and controls
Age (years) Gender (male/female) BMI (kg/m2 ) Waist (cm) Glucose (mg/dL) Serum Uric acid (mg/dL) Creatinine (mg/dL) HDL-Cholesterol (mg/dL) Triglycerides (mg/dL) CRP (mg/L) Fibrinogen (mg/dL) Leucocytes (106 /L) Neutrophils (103 /L) Insulin (U/mL) HOMA
Metabolic syndrome n = 71
Control n = 122
p
41 ± 12 49/22 32.9 ± 4.6 110.2 ± 11.4 120 ± 34 6.2 ± 1.5 0.88 ± 0.18 48 ± 12 176 ± 73 5.56 ± 8.64 367 ± 75 7.22 ± 1.68 4.17 ± 1.37 18.59 ± 12.09 9.18 ± 25.35
45 ± 11 73/49 26.2 ± 3.8 91.6 ± 10.8 95 ± 14 5.2 ± 1.3 0.86 ± 0.16 59 ± 14 99 ± 41 1.75 ± 1.98 312 ± 55 6.03 ± 1.68 3.32 ± 1.21 7.25 ± 3.69 1.82 ± 1.02
0.060 0.202
