A cohort study to find Incidence of Peripheral Arterial Disease in

Transcription

1 A cohort study to find Incidence of Peripheral Arterial Disease in Thailand from EGAT study (I PAD EGAT) Uraporn Jaowattana, MD Fellowship in Cardiology, Ramathibodi Hospital

2 Background and Rationale Peripheral Arterial Disease (PAD) is one of burden diseases Systemic atherosclerosis Causes morbidity and mortality worldwide PAD is considered to be an established CAD equivalent. By year 2020, PAD will surely be one of the globally burden diseases.

3 Poor Outcomes of PAD Chronic Limb Ischemia(CLI): is pain in lower extremity at rest or ulceration with or without tissue necrosis. Acute Limb Ischemia (ALI) : presents within hours with rest limb pain and a pulseless, painful foot. The vessel is occluded with a thrombus on top of mild to severe lesions.ali is a result from plaque rupture followed by in situ thrombosis or migration of a clot from proximal location.

4 PAD mortality : 10 year survival rates the San Diego Artery At Study Normal Surv vival Asymptomatic Symptomatic Severe symptomatic Time (years) Criqui MH et al. N Engl J Med 1992;326:

5 In USA, the incidence of symptomatic Peripheral Vascular Disease(PVD) increases with age from about 0.3% per year for men aged years to about 1% per year for men aged over 75 years.

6 In Thailand, the study data on PAD is still scant, even we had been enrolled in the REACH registry trial.

7 REACH Study( n= 68,236) North America: 27, Canada: 1,976 USA: 25,770 Latin America: 1,931 Brazil: 441 Chile: 253 Mexico: 899 Interlatina : 338 Europe: 23,542 Austria: 1,588 Lithuania: 99 Belgium: 383 The Netherlands: 324 Bulgaria: 996 Portugal: 218 Denmark: 422 Romania: 2,009 Finland: 311 Russia: 999 France: 4,592 Spain: 2,515 Germany: 5,521 Switzerland: 695 Greece: 699 Ukraine: 596 Hungary: 957 United Kingdom: 618 Middle East: 846 Israel: 379 Kingdom of Saudi Arabia: 198 Lebanon: 120 United Arab Emirates: 149 Asia China: 708 Hong Kong:175 Indonesia: 499 Japan: 5,048 Malaysia: 525 Phillippines: 1,039 Singapore: 880 South Korea: 505 Taiwan: 1,057 Thailand: 515 Australia: 2,872

8 PAD burden internationally REACH STUDY Reduction of Atherothrombosis for Continued Health (REACH) Registry 68,236 patients with either known atherosclerotic arterial disease (n= 55,814) or at least had 3 risk factors for atherothrombosis (n=12,422) from 5, practices in 44 countries ti in December 2003 June2004. AmHeart J. 2006;151: 786.e1 786.e10.

9 PAD Prevalence 18.3% in UK 19.1% in Netherlands 18% in Germany and Sweden, ranging gfrom % in US from different studies 19.8% in China 11.7% in Saudi Arabic 10.5% in Spain 29.3% in South Africa 3.2% South India 5.2% in Thailand Review: Ethnicity and peripheral artery disease,q J Med 2009; 102:3 16 Sritara, P. International Epidemiology Journal, 2003.

10 REACH Study Demonstrated that PAD patients had high prevalence of underlying vascular disease, multiple atherothrombotic risk factors. Found that there was underutilization in treating cardiovascular risk

11 PAD prevalence in Thailand 5.2% * * Sritara, P. International Epidemiology Journal, 2003.

12 EGAT 2002 In Thailand, from EGAT employee Overall prevalence of PAD was 5.2%,with finding of 4% in male and 9% in female. Hypertension, women, current smoking, current alcohol drinking and overweight have been found to be significant predictors of PAD * Sritara, P. International Epidemiology Journal, 2003.

13 Incidence of PAD from EGAT populations

14 I PAD EGAT Inclusion Criteria: All of the Employee from previous EGAT study population p in 2002

15 I PAD EGAT Exclusion: Loss of contact and not followed up in this study

16 Objectives Primary objective To find PAD incidence from EGAT study Secondary objectives To estimate prevalence of PAD fromegat To assess influence of RFs on new PAD development To find mean CAVI value ( indicate arterial stiffness)

17 Methodology Cohort study EGAT study subjects without PAD at Follow up on PAD diagnosis at year 2012.

18 Populations Population Elderly age 50 74, middle class, urban Study sample All EGAT employee who are available in former and this EGAT study.

19 Definition Peripheral artery disease (PAD) Year 10 th PAD Cumulative 10 years PAD

20 Operational Definitions PAD Asymptomatic PAD Lowest resting ABI<0.9 PAD + no leg symptom IC i Typical Calf pain while walking Disappears in 10 min after standing still Never occurs at rest Atypical Exertional leg pain other than calf i Rose GA. Bull WHO 1962;27:

21 Operational Definitions Diabetes i Hypercholeste FBG>126 mg/dl or on hypoglycemic Rx TC 240 mg/dl or on lipid-lowering lowering Rx rolaemia ii Hypertension iii Systolic BP 140 mmhg or diastolic BP 90 mmhg or on antihypertensive Rx i ADA. Diabetes Care 2000;23(Suppl 1):s20-3 ii NCEP III. JAMA 2001;285: iii 1999 WHO/ISH. J Hypertens 2001;19(12):2285-8

22 Operational Definitions Thais Current smoker Current alcohol drinker Individuals who had lived in Thailand for >17 yrs Individuals who currently smoke >1 cigarette per day for at least 1 yr Individuals who currently take >1 drink of alcohol beverage at least once a month for at least 1 yr

23 I PAD EGAT Diagnosis of Peripheral Arterial Disease: ABI <0.9 is made for the diagnosis of PAD in this study. normal ABI ( )

24 ABI ADA & AHA 5 min rest, quiet and supine Angle probe 60 degrees Move probe back & forth Inflate>20 mmhg Slow deflation: 2mmHg/sec Syst BP: 1 st signal during deflation ADA & AHA. Circulation 1993;88 88(2): ): Pocket Doppler MINIDOP ES100VX

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31 Statistical Methods Descriptive i statistic i (mean, SD, percent) for subject characteristics explanation and incidence analysis. KS test for normal distribution test. Z test to demonstrate mean of ABI and CAVI. Paired T test to test difference b/w ABI 2002 and ABI 2012, ABI and CAVI at 2012 Univariate and multivariate logistic regression for demonstrating the predictor of peripheral artery disease (PAD) in elderly.

32 Statistical Methods Univariate and multivariate logistic regression for demonstrating the predictor of peripheral p artery disease (PAD) in elderly.

33 Study Results

34 2002 2,209 EGAT employee No PAD from normal ABI ,427 with previous normal ABI 1,387 with complete data of ABI this year follow up

35 1,427 EGAT study employee who had no peripheral artery disease at 2002 (ABI 0.9) 40 subjects were excluded because of unavailable ABI at A total 1,387 employee for research analysis.

36 Baseline ABI 38 subjects (2.74%) from 1,387 subjects that they had ABI < 0.9 at subjects were considered as the subjects whohad had peripheral artery disease for this research. Normal distribution test >> Not acceptable (K S test, 2002 p value and 2012 p value <0.001)

37 10 years PAD Incidence Unstandardized : 2.74 % (n=1,387) Age adjusted : 2.86% (based on n= 80,642) Sex adjusted: 2.65% (based on n=2,418)

38 Baseline of cardiovascular risks characteristics Mean+ SD n n % Age at 2002 (years) (n=1,387) Age group(n=1 1,387) Y % 20% % % equal or more than % Gender (n=1,387) Female % Male % Hypertension (n=1,387) Have no hypertension % Have hypertension % Smoking (n=1,370) Nonsmoker % Smoker (Both current and % former) Diabetes mellitus Have no Diabetes mellitus % (n=1,384) Have Diabetes mellitus %

39 Baseline of cardiovascular risks characteristics Mean+ SD n n% Stroke (n=1,387) Have not experienced stroke % Have experienced stroke % Dyslipidemia id i (n=1,387) Have no dyslipidemia id i % 37% Have dyslipidemia % Coronary artery stenosis Have no previous coronary % (n=1,387) artery stenosis Have previous coronary artery stenosis % Previous myocardial Have no previous MI % infarction (n=1,387) Have previous MI % Weight (kg) (n=1,361) Height (cm) (n=1,361) BMI (kg/m 2 ) (n=1,361) BMI (n=1,361) Normal (BMI < 25) % Overweight (30> BMI >= 25) % Obesity (BMI >= 30) %

40 Baseline of cardiovascular risks characteristics Mean+ SD n n % Age risk (n=1,387) Male <= 55 and Female <=65 years % Male > 55 and Female > 65 years % Chronic Kidney No CKD as underlying disease % Disease (n= 1,387) Have CKD as underlying disease % GFR (ml/min) (n=1,370) GFR (n=1,370) Normal GFR % Abnormal GFR (< 60 ml/min) % Blood pressure test Normal BP both assessments % assessment High BP >140/90 for 2 times of % (n=1,377) assessments.

41 Baseline of cardiovascular risks characteristics Mean+ SD n n % Resting blood pressure assessment 1 st blood pressure assessment (n= 1,382) Systolic blood pressure (mmhg) Systolic blood SBP1 Normal % pressure SBP1 >140 mmhg % Dystolic blood pressure (mmhg) Dystolic blood DBP1 normal % pressure DBP1 > 90 mmhg % Blood pressure Normal BP % Abnormal BP1 (>140/90) %

42 Baseline of cardiovascular risks characteristics Mean+ SD n n % 2 nd blood pressure assessment (n= 1,377) Systolic blood pressure (mmhg) Systolic blood SBP2 Normal % pressure SBP2 >140 mmhg % Dystolic blood pressure (mmhg) Dystolic blood DBP2 normal % pressure DBP2 > 90 mmhg % Blood pressure Normal BP % Abnormal BP2 (>140/90) %

43 Baseline of cardiovascular risks characteristics Cardio-Ankle Vascular Index 2012 (CAVI) (n=1,377) Right CAVI score Left CAVI score Mean+ SD n n % CAVI criteria Normal (CAVI score 8.0) % Ankle Brachial Index at 2002 Ankle Brachial Index Border line (9 > CAVI >=8 ) % Possible CAVI >=9 Arteroisclerosis % Normal 1, % (n=1,387) Abnormal (ABI <0.9) % 00% Ankle Brachial Index at 2012 Ankle Brachial Index Normal % (n=1,387) Abnormal (ABI <0.9) %

44 Baseline of cardiovascular risks characteristics Ankle Brachial Index at 2002 Left Ankle Brachial Index (n=1,387) Mean+ SD n n % Left Ankle Brachial Index Normal 1, % 00% Abnormal (ABI <0.9) % Right Ankle Brachial Index (n=1,387) Right Ankle Brachial Index Normal 1, % Ankle Brachial Index (n=1,387) Ankle Brachial Index at 2012 Abnormal (ABI <0.9) % Normal 1, % Abnormal (ABI <0.9) % Left Ankle Brachial Index (n=1,387) Right Ankle Brachial Index (n=1,387) Ankle Brachial Index (n=1,387) Normal % Abnormal (ABI <0.9) %

45 Baseline of cardiovascular risks characteristics Fasting blood glucose (FBS) and HbA1C Test Fasting blood glucose (FBS) (mg/dl) Test (n=1,386) Mean+ SD n n % Fasting blood glucose Normal % Abnormal (FBS >=126) % HbA1C (n=1,386) HbA1C Normal % Abnormal (HbA1C > 6.5%) %

46 Baseline of cardiovascular risks characteristics Mean+ SD n n % Lipid profile test Total Cholesterol (n=1,386) Cholesterol level Less than 240 mg/dl % Equal or more than 240 mg/dl % Triglyceride (n=1,386) Triglyceride level Less than 200 mg/dl % Equal or more than 200 mg/dl % HDLC (n=1,386) HDLC level Equal or more than 40 mg/dl % Less than 40 mg/dl % LDLC (n=1,386) LDLC level Less than160 mg/dl % Equal or more than 160 mg/dl % Lipid Profile test Normal lipid profile test % (n=1,386) Abnormal lipid profile test %

47 Univariate analysis Demonstrate predictors of year 10 th PAD Univariate logistic regression results: >> Significant risks of Year 10 th PAD 1. Dyslipidemia 2. Male with more 55or female more 65years 3. Chronic kidney disease 4. FBS equal or more than 126 mg/dl 5. HbA1C more than 6.5% 6. Triglyceride equal or more than 200 mg/dl 7. HDLC less than 40 mg/dl 8. Stroke History

48 Univariate analysis results Risks N Year 10 PAD n (%) Odd ratio 95%CI p-value Age 1, % to * Age group (n=1,387) Y % Reference % to % to equal or more than % to Gender (n=1,387) Female % Reference Hypertension (n=1,387) Male % to Have no hypertension % Reference Have hypertension % to Smoking (n=1,370) Nonsmoker % Reference Smoker % to Diabetes mellitus No % Reference (n=1,384) Yes % to

49 Univariate analysis Demonstrate predictors of year 10 th PAD Risks N Year 10 PAD n (%) Odd ratio 95%CI Stroke (n=1,387) No % Reference p-value Yes % to Dyslipidemia (n=1,387) No % Reference Previous CAD (n=1,387) Yes % to No % Yes % BMI (n=1,361) Normal weight % Reference Male > 55 or Female > 65 years (n=1,387) Over weight % to Obesity % to No % Reference Yes % to CKD No CKD % Reference (n= 1,387) Have CKD % to <0.001

50 Univariate analysis Demonstrate predictors of year 10 th PAD Risks N Year 10 PAD n (%) Odd ratio 95%CI GFR (n=1,370) >=60 ml/min % Reference BP assessment < 60 ml/min % to <=140/90 mmhg % Reference p-value (2times) (n=1,377) >140/90 mmhg % to Fasting blood glucose (n=1,386) < 126 mg/dl % Reference >=126 mg/dl % to <0.001 HbA1C (n=1,386) <=6.5% % Reference > 6.5% % to FBS /HbA1C (n=1,386) < 126 mg/dl and <=6.5% % Reference >=126 mg/dl and/or > % to % 6.5%

51 Univariate analysis Demonstrate predictors of year 10 th PAD Risks N Year 10 PAD Odd ratio n (%) 95%CI p-value Cholesterol level < 240 mg/dl % Reference (n=1,386) >= 240 mg/dl % to Triglyceride level < 200 mg/dl % Reference (n=1,386) >= 200 mg/dl % to HDLC level >= 40 mg/dl % Reference (n=1,386) < 40 mg/dl % to <0.001 LDLC level (n=1,386) <160 mg/dl % Reference >= 160 mg/dl % to Lipid Profile test Normal % Reference (n=1,386) Abnormal % to

52 Multivariate analysis Multivariate logistic regression analysis, backward stepwise method Predictors from univariate analysis with p value < 0.10 were entered in the multivariate analysis 1. Age 2. Hypertension 3. Dyslipidemia 4. Male with more 55 or female more 65 years 5. Chronic kidney disease 6. GFR abnormality 7. Triglyceride abnormality 8. HDLC abnormality 9. Fasting blood sugar or HbA1C abnormality 10. Stroke/TIA History A total subjects who had completed data were A total 1,370 subjects who had completed data were analyzed.

53 Multivariate analysis The significant predictors of year 10 th PAD were 1. Chronic kidney disease 2. FBS >=126 mg/dl and/or HbA1C > 6.5% 3. Dyslipidemia 4. HDL cholesterol (<40 mg/dl) 5. Stroke /TIA history Age also was a important factor.

54 Multivariate analysis B S.E. Wald Sig. Odd ratio 95 % C.I. Age * 058* Dyslipidemia * HDL < 40 mg/dl * FBS >=126 mg/dl * and/or HbA1C > 6.5% Chronic kidney disease * Stroke * Constant

55 Relationship between changes of ABI and PAD Mean different Changes of ABI for ten years (n=1,387) %CI= to The changes of ABI were divided in to 3 equal groups at Percentiles = and Percentiles = 0.01 Group 1 ABI increased from baseline more than Group 2 ABI increased from baseline equal or less than 0.01 but not decreased from baseline more than Group 3 ABI decreased from baseline equal or more than 0.08.

56 Relationship between changes of ABI and PAD Pearson chi square used for analysis relationship between PAD and changes of ABI. The previous ABI changes group 1 and group 2 were integrated into the same group. Group 1 =ABI decreased from baseline less than 0.08 Group 2= ABI decreased from baseline equal or more than 0.08 ABI 2012 Decreased < 0.08 (N= 857) Decreased > = 0.08 (N=481) 2012 ABI > = 0.9 Considered as no PAD (N=1,349) Count ABI < 0.9 considered as PAD (N=38) Row Column Table Column Table Count Row N % N% N% N% N% N% % % 65.68% 63.88% % 2.63% 0.07% 34.32% 32% 33.38% 38% % 97.37% 2.67% Pearson chi square analysis shown significant difference between PAD and ABI changes (p value <0.001).

57 Relationship between changes of ABI and Risk factors Relationship between the ABI changes groups and 5 significant risks of PAD from multivariate analysis were also analyzed by Pearson chi square. The results shown significant relation between HDL Cholesterol level and the ABI changes groups (p value = 0.024) and between fasting blood sugar level and/or HbA1C > 6.5% and the ABI changes groups (p value = 0.027). Changes of ABI Peripheral artery disease diagnosed at next 10 years Column N N Group 1 Group 2 ABI decreased from baseline ABI decreased from baseline less than equal or more than 0.08 No (65.7%) 463 (34.3%) Yes 38 1 (2.6%) 37(97.4%) Stroke No (64.2%) 487(35.8%) 8%) Yes 27 14(51.9%) 13 (48.1%) Dyslipidemia No (62.81%) 167 (37.19%) Yes (64.5%) 333 (35.5%) Chronic kidney No (64.4%) 4%) 481 (35.6%) disease Yes (48.6%) 19 (51.4%) HDLC < 40 mg/dl No (64.8%) 455 (35.2%) Yes 93 49(52.7%) 44(47.3%) FBS >=126 mg/dl No (65.3%) 405 (34.7%) and/or HbA1C > 6.5% Yes (57.3%) 94 (42.7%) p-value a <0.001* * 0.029*

58 Relationship between Cardio ankle vascular index (CAVI) and PAD Cardio-ankle vascular index (CAVI) mean between patients with PAD and without PAD was compared by t-test. There was no significant difference of CAVI between the patients who had PAD diagnosed by ABI. Peripheral artery disease diagnosed Cardio-ankle vascular index ABI >= 0.9 ABI < 0.9 No Yes n 1, Mean + SD N of Age adjusted 78,663 Mean + SD Cardio-ankle vascular index criteria N(%) Normal (CAVI < 8.0) (96.6%) 6%) 6(34%) (3.4%) Border line and (9 > CAVI >=8 ) (97.0%) 12 (3.0%) Possible Arteroisclerosis (CAVI >=9) (97.5%) 20 (2.5%) a t-test b Pearson chi-square p-value a 2, <0.001* b

59 Conclusion Incidence of PAD diagnosed by abnormal ABI <0.9, in the past 10 years from EGAT population was 2.74%.

60 Univariate analysis Significant RFs for year 10 th PAD were dyslipidemia,male with more 55 or female more 65 years, CKD, FBS 126 mg/dl, HbA1C > 6.5%,Triglyceride 200 mg/d,hdl <40 mg/dl,stroke history

61 Multivariate analysis The significant predictors of year 10 th PAD were 1. Chronic kidney disease 2. FBS >=126 mg/dl and/or HbA1C > 6.5% 3. Dyslipidemia 4. HDL cholesterol (<40 mg/dl) 5. Stroke /TIA history Age was also important.

62 Delta change of ABI When the change value decreases more than 0.08, it relates to the development of PAD in thenext10 years. Risk factors: FBS >= 126mg/dl, HDL<40 mg/dl

63 Limitations of the study There is no ethinicity difference. This represents only the middle class populations for Thailand Limited i number of patients who have been followed up in both times.

64 Special Thanks and Acknowledgement อาจารย นพ ป ยะม ตร และ อาจารย พญ ชน กา ศร ธรา อาจารย นพ สก จ แย มวงษ อาจารย นพ ปร ญญ วาท สาธกก จ ท มงานว จ ย EGAT