Age and Homocystein were Risk Factor for Peripheral Arterial Disease

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Proyeksi penduduk Indonesia (Indonesia population projection) 2000-2025. Jakarta: Badan Perencanaan. Pembangunan Nasional, BPS, United Nations ...
ORIGINAL ARTICLE

Age and Homocystein were Risk Factor for Peripheral Arterial Disease in Elderly with Type 2 Diabetes Mellitus RA. Tuty Kuswardhani, Ketut Suastika

Department of Internal Medicine, Faculty of Medicine, Udayana University - Sanglah Hospital. Jl. PB Sudirman, Denpasar Bali, Indonesia. Correspondence mail to: [email protected]

ABSTRACT Aim: to find out the magnitude of risk of some traditional and non-traditional risk factors for PAD event in the elderly with Type 2 diabetes mellitus (T2DM) patients. Methods: a case-control study involved 40 subjects of each arms (case and control group) at Geriatric Outpatient Clinic Sanglah Hospital, Denpasar, Bali, Indonesia was conducted. Results: the study showed that compared to patients wihout PAD, patients with PAD had higher age (70.7 vs. 65.0 years; p60 years. The projection of elderly population in Indonesia by the year 2010 will be 23.992.552.1 US Bureau of Census predicted that from 1990 to 2020, the Indonesian elderly population will increase 414%. 2 Indonesia as the country with the biggest forth of elderly population in the world after China, India, and USA.1 Peripheral arterial disease (PAD), a marker of systemic atherosclerosis, is frequently related with age.3 It mostly starts at age 40 and sharply increases after age 70 years. Althoug in general the mechanism of PAD is similar to that of coronary atherosclerosis, they have somewhat different in the role of some risk factors. Commonly, these factors can be differentiated into traditional (such as hypercholesterolemia, hypertension, Type 2 diabetes mellitus [Type 2 DM], and smoking) and non-traditional (or novel) risk factors.4-6 Several studies reviewed by Kuswardhani (2007) found out that prevalence of PAD ranged from 16 to 30%.7 Some of novel risk factos for PAD are transforming growth factor β (TGF-β), vascular cellular adhesion molecule (VCAM), apoptotic inducer (Fas ligand), assymetric dimethylarginine (ADMA), soluble vascular adhesion molecule 1 (sVCAM-1), high sensitive C Reactive Protein (hs CRP), and homocystein.8-16 Up to now, only a few data are available regarding risk factors for PAD especially among the elderly with Type 2 DM population in Indonesia. And also no any data has published concerning the association of nontraditional risk factors (homocystein and ADMA) for PAD in the elderly with Type 2 DM in Indonesia. This study aim is want to know the role of some traditional and non-traditional risk factors (homocystein and ADMA) for PAD in the elderly with Type 2 DM.

Vol 42 • Number 2 • April 2010

Age and Homocystein were Risk Factor for Peripheral Arterial Disease

METHODS

To find out the magnitude of some risk factors to PAD event in the elderly (>60 years) patients with Type 2 DM, a case-control study involving 40 patients each arms (case and control groups) at Geriatric Outpatient Clinic Sanglah Hospital, Denpasar, Bali, Indonesia was conducted. PAD was diagnosed if ankle-brachial index (ABI) was lower than 0.9; DM was confirmed by ADA (2009) criteria.17 For calculating the minimal number of sample each arms in case-control study was used formula as follow (Kirkwood).18

n >

{µ V[n1(1- n1) + n2(1- n2)] + v V[2n3(1- n3)]}2 —————————————————— (n2 - n1)2

n3= n1 + n2; n1 = proporsion of control with high plasma homocystein concentration (0,1); n2 = proporsion of case with high plasma homocystein concentration (0,4); µ = 0.8 (beta 0.20); v = 1.64 (alfa 0.05); minimal number of sample in each arms was 29 patients. Subjects with smoking, acute cardiovascular (coronary and stroke) events, acute infections, acute and chronic hepatic failure (SGOT and SGPT >2X normal range), malingancy, acute or chronic kidney disease with creatinine serum >3 mg/dl or CCT 90 cm for men and >80 cm for women, high body mass index

(overweight or obese) was >23 kg/m2, systolic blood pressure >130 mmHg, high diastolic blood pressure was >90 mmHg, hypertension was blood pressure >130/90 mmHg, high concentrations of total cholesterol was >200 mg/dl, high LDL-cholesterol was >100 mg/dl, low HDL-cholesterol was 126 mg/dl, high 2hpp plasma glucose was >200 mg/dl, high A1C was >7%, longterm duration of diabetes was >5 years, high concentration of homocystein was >12 µmol/L and high ADMA was >0,75μmol/L. The data were analyzed by chi-square test to define the difference of a variable (risk factor) between case and control group, and odds ratio value was calculated to determin the magnitude of risk a variable (risk factor) for PAD event. Multivariate analysis by logistic regression forward stepwise (conditional) was used to know the role some risk factor for PAD event. All analysis using software SPSS 15.0, with significant values was confirmed by p11 µmol/L (based on ROC analysis, by sensitivity = 0.700 and 1-spesificity = 0.450, the cut of point of homocystein level as risk for PAD event was 11 µmol/L ) (Figure 1), high homocystein level (>11 µmol/L) 2.5 time has risk for PAD compared to normal level (OR = 2,538; CI = 1.023-6.298; p = 0.043) (Table 3). 1.0

0.8

Sensitivity

groups (Table 1). Although no any significant difference, subjects with PAD tend to doing exercise less prevalent, consumed anti-hyperlipidemic and antithrombotic more frequent compared to subjects without PAD (Table 2).

0.6

0.4

0.2

0.0 0.0

0.2

0.4

0.6

96

1.0

Figure 1. ROC curve of homocystein levels to PAD event. By sensitivity, 0.700 and 1-spesicity, 0.450; was found that cut of point of homocystein level as risk factor for PAD event was 11 mmol/L

Table 3. Odds ratio of risk factors for PAD event Risk factors

OR

95% CI

p

Age (60-69 vs. 70-80) Wist circumference (normal vs. obese) Body mass index (non-obese vs. obese) Lying systolic blood pressure (normal vs. high) Sitting systolic blood pressure (normal vs. high) Standing systolic blood pressure (normal vs. high) Lying diastolic blood pressure (normal vs. high) Sitting diastolic blood pressure (normal vs. high) Standing diastolic blood pressure (normal vs. high Lying hypertension (normotension vs. hypertension) Sitting hypertension (normotension vs. hypertension) Standing hypertension (normotension vs. hypertension) Total – cholesterol (normal vs. high) LDL-cholesterol (normal vs. high) HDL-cholesterol (normal vs. low) Triglyceride (normal vs. high) Fasting plasma glucose (normal vs. high) 2hpp plasma glucose (normal vs. high) A1C (normal vs. high) Duratio of diabetes (