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Ischemic Heart Disease in Pakistani Women: A Case Control Study

Ischemic Heart Disease in Pakistani Women: A Case Control Study

Correspondence: Rafia Rafique New Campus, Lahore, Pakistan Cell: 042-3004215694 Email: rafiawaqar@hotmail.com Coauthor email: naumana_a@hotmail.com

ABSTRACT Objective: Control of Ischemic Heart Disease (IHD) in Pakistan has had limited success mainly due to insufficient research data available from studies conducted on Pakistani population, especially on a sample of women. Women tend to differ from men clinically as well as in the overt disease manifestation, pointing towards a need to conduct gender specific studies to investigate risk factors of IHD. Consequently this study was designed to investigate factors associated with risk of early onset IHD in a sample of Pakistani women.

Method: Case control study design was utilized to explore the association of family history of IHD, diabetes, hypertension and anthropometric measurements (waist circumference, Body Mass Index (BMI) and Waist Hip Ratio (WHR) with risk of IHD in women aged 35 to 55 years. A sample of 71 women cases diagnosed with IHD and 142 age and gender matched community controls were recruited for this purpose. Self-reported information regarding family history of IHD, diabetes and hypertension was gathered. Moreover height, waist and hip circumference were measured in centimeters, (by using a non-stretchable standard tape with a metal buckle at one end over the light clothing), weight was assessed in kilograms. Results: Binary logistic regression analysis was conducted to ascertain the association of proposed factors with the risk of IHD, and the results revealed that in women aged 35 to 55 years, BMI ≥ 25 kg/m2 and WHR ≥ 0.84 were significant risk predictors of IHD. Conclusion: Well designed studies need to be carried out for endorsement of risk factors for IHD in Pakistani women; secondly instituting gender specific preventive care can alter these risk factors to save Pakistani women. KEY WORDS: Ischemic heart disease, anthropometric measurements, binary logistic regression INTRODUCTION Cardiovascular disease (CVD) is reported to be the principal cause of mortality in parts of Karachi, Pakistan.1The greatest concern of Pakistan is that CVD emerges at an earlier age than that in the west and hence mortality ratios as compared to other ethnic groups is highest in the younger South Asians.2,3,4 There is ample evidence that documents an earlier onset of IHD in Pakistani population.5,6,7 Researchers document that 16.1% of the overall population with IHD in Pakistan are less than 45 years of age 8 and 19% of the patients diagnosed with IHD were less than 40 years. 9 Jafary et al. (2007) found mean age of patients in their study to be 52.5±10.8 years, however only 22.5% reported being 60 years or older. 10 However evidence from a population-based cross sectional survey carried out in Pakistan has identified equal prevalence of IHD across gender within the indigenous population.11 Limited research efforts have been undertaken to explore factors associated with risk of IHD in Pakistani women. Globally it is documented that IHD has multi-factorial etiology and many factors like increased BMI, WHR, 12 hypertension and diabetes determine the risk of IHD.13 Despite the fact that the onset of IHD occurs 10 year earlier in south Asian countries, including Pakistan,14very few studies have shed light on the reasons for early onset of disease in developing countries like Pakistan. Research on risk factors for IHD are largely derived from developed countries, and may risk factors vary between populations, and differ due to ethnic diversity. The irresolution in research findings from the Western and European population about the documented risk factors of IHD like greater BMI, increased WHR, family history of IHD, diabetes, hypertension 2,12,13 remain questionable in terms of applications to rest of the world. In Pakistan, control of CVD has had limited success.15 First, there is insufficient research data regarding cardiac risk factors prevalent within the indigenous population. Research data from few studies conducted on Pakistani population is limited to bio-behavioral risk factors of IHD. 16,17,18,19 Second, studies designed to explore risk factors of IHD have largely recruited males and thus have excluded risk factors that affect women. METHODS Sample To investigate the association of factors with risk of IHD, 71 women patients with confirmed diagnosis of IHD and 142 community controls matched on age, who were free of IHD before and at the time of testing, were recruited. The cases recruited were patients with the first onset of IHD {Angina and Myocardial Infarction (MI)} presenting within 24 hours of symptoms, admitted to the coronary care unit or the equivalent cardiology ward of the hospitals. Likewise two age and gender matched community controls (up to 5 years older or younger, aged 35 to 55 years) were drawn directly from special subgroups in the community who had some relationship to the cases (such as friends, neighbors’ and non-blood relatives).  Community controls were study participants who had particular characteristics like the cases (age and gender), but had not yet developed the disease under investigation. Eligibility criteria: We recruited cases if they had one episode of Angina with chest pain as determined by cardiologists. Furthermore, patients with chest pain established as Angina through exercise, ECG, or cardiologist’s summary and symptom scores were also recruited in this study. In addition, patients with the first onset of acute myocardial infarction (AMI), whose diagnoses have been confirmed by the cardiologists on the basis of clinical symptoms or changes in electrocardiogram, or raised concentration of troponin levels, were included in the study. Exclusion criteria: Patients experiencing the following sign and symptoms were not included in the study sample: patients who had undergone cardiogenic shock or chest pain due to non-cardiac reasons; patients suffering from any of the significant chronic medical illness including: liver disease, hyperthyroidism or hypothyroidism, renal disease, malignant disease; pregnant females, as well as patients with a prior history of any psychiatric diagnosis or those who were currently on any antipsychotic medication Patients who had a previous history of treatment for heart disease like percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft (CABG) surgery; participants failing to provide informed consent (as these conditions modify the risk factors in IHD and might have an impact on behavior and lifestyle), and patients who were unable to read or write Urdu (national) language were not included in the study. Community-based controls recruited in the study were attendants, visitors or relatives of the cardiac patient, unrelated (not first-degree blood relatives) having no previous diagnosis of heart disease or history of exertional chest pain. Exclusion criteria followed for community controls was the same as that set up for the cases. Self-reported information regarding family history of IHD and self reported medical factors namely diabetes and hypertension was gathered. The family history of IHD included information regarding the presence of IHD in parents and siblings of the study participants before the age of 55 years. Anthropometric measurements: Height, waist and hip circumference were measured in centimeters, (by using a non-stretchable standard tape with a metal buckle at one end over the light clothing), weight was assessed in kilograms. Waist circumference was measured in the center of the iliac crest and the coastal margin (lower rib), and hip circumference was measured at the widest point on buttocks below the iliac crest. Waist and hip circumferences of every study participant were taken to calculate WHR. Cutoffs for WHR and BMI were calculated separately for analysis; these cutoffs were based on the control data. Procedure: Approval by regulatory and ethics committee from all the five hospitals prior to initiating the research was sought by the researcher. Written consent form was prepared in Urdu and was given to participants for signature before they could take part in this study. All participants were briefed about the purpose of the study and were assured about the confidentiality and privacy of their responses. Participants were told that they were free to leave the study anytime if they felt uncomfortable and that this would not incur any prejudice or penalty to them. Similar set of procedures were carried out with controls. For every case two age and gender matched community controls were recruited either that very day or at the maximum within a week. Once the participants had participated in the study the researcher thanked and debriefed the participants about the nature of the study. Statistical Analysis: Unconditional binary logistic regression analyses were conducted by using the forward conditional method to infer the association of factors with risk of IHD. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) for family history of IHD and self-reported physical health factors (diabetes and hypertension). Another regression model was built to ascertain association of anthropometric factors with risk of IHD. Odds ratios represented the excess risk of exposure to a factor in cases compared with controls, without exposure. In the case of binary or ordinal variables a reference category with minimal risk was taken. Table I Cross Tabulation of Self Reported Physical Health Factors, Family History and IHD

Case/Control Status

Case

Control χ²

p

Hypertension
Present

44

(38.8)

72

(77.2)

.14*

.08

                                      Absent

27

(32.2)

69

(63.8)

Family history of Hypertension
Present

35

(37.5)

77

(74.5)

.47

.27

                                   Absent

36

(33.5)

64

(66.5)

Diabetes

Present

29

(24.8)

45

(49.2)

.22

.12

Absent

42

(46.2)

96

(91.8)

Family history of Diabetes
Present

36

(37.2)

75

(73.8)

.77

.42

                                   Absent

35

(33.8)

66

(67.2)

Family history of IHD

Present

35

(30.1)

55

(59.9)

0.18

0.10

Absent

36

(40.9)

86

(81.1)

Note. Mean age at which hypertension was diagnosed was 35.90 for cases and that for controls was 36.42.Mean age at which diabetes was diagnosed was 38.16 for the cases and 40.92for the controls. The results of Chi square reveal that there is no significant association between self reported health factors, family history of hypertension, diabetes and IHD with IHD. Table 2 Description of the Study Sample on Anthropometric Measurements

 

Women cases

       Women controls
Variable M(SD) Range M(SD) Range
Waist 90.41cm (11.38)

66.0-111.80

83.54cm (9.51)

66.00-111.80

Hip 101.54cm(11.38)

76.20-127.00

98.76cm(9.00)

76.20-124.50

WHR 0.89cm (0.05)

0.80-1.05

0.84cm(0.05)

0.76-1.03

Weight 69.03kg(14.39)

50-157.50

65.57kg(7.67)

48.00-96.30

Height 156.76cm(13.66)

59.42-172.72

162.10cm(8.79)

118.00-177.80

BMI 26.96(3.99)

19.70-37.90

24.43 (2.66)

16.10-38.30

Note. Waist circumference, hip circumference and height were measured in centimeters (cm), and weight in kilograms (kg). Table 3 Cross Tabulation of Anthropometric factors and IHD

Case/Control Status

Case

Control χ²

p

WHR

< 0.84cm

27.5

(82)

71

(54.5)

 

 

.00

 

 

.00

≥ 0.84cm

60

(43.5)

70

(86.5)

BMI

< 25 kg/m2

28

(45.2)

109

(91.8)

 

 

.00

 

 

.00

≥ 25 kg/m2

38

(20.8)

25

(42.2)

Waist Circumference

< 84cm

24

(39.5)

94

(78.5)

 

 

.00

 

 

.00

≥ 84cm

47

(31.5)

47

(62.5)

Note. Significant associations between WHR, BMI, Waist circumference and IHD were revealed when  χ²test was conducted. Table 4 Anthropometric Factors Independently Associated with IHD

Variable   B(SE) Exp (B)OR (95% CI)
Step 1Constant -1.36***(0.21)
BMI (kg/m2)< 25 1
       ≥ 25 1.78***(0.33) 5.91(3.07 – 11.37)
Step 2Constant -2.09***(0.34)
BMI (kg/m2)< 25 1
       ≥ 25 1.41***(0.35) 4.11(2.06 – 8.19)
WHR< 0.84 1
      ≥ 0.84 1.28***(0.39) 3.59(1.65 – 7.78)

Note. Women cases and women control data adjusted for age. Waist circumference (< 84, and ≥ 84) WHR (< 0.84 and ≥ 0.84) and BMI (< 25 kg/m2 and ≥ 25 kg/m2) ***p < .001. A Forward Stepwise Binary Logistic Regression on women cases and women controls was conducted with IHD as the DV and family history of IHD and physical health factors (diabetes and hypertension), as IV. Non-significant results were found for all three self-reported factors, diabetes, hypertension, and family history of IHD. They were not significant predictors of IHD in women. Another Binary logistic regression analysis was performed to ascertain anthropometric factors independently associated with IHD in women by using forward conditional method, with IHD as the DV and three measures of clinical obesity; BMI, waist circumference and WHR as predictor variables. A total of  200 women cases and controls were analyzed and the full model significantly predicted presence of IHD (Omnibus Chi-square =41.69, df = 2, p <.001) (see Table 4).The model accounted for between 18 % and 27 % of variance in IHD, Overall 74% of the predictions were accurate. BMI ≥ 25 kg/m2 was found to be a significant predictor of IHD in women. The values of the coefficients revealed that BMI ≥ 25 kg/m2 is associated with increase in odds of IHD by a factor of 4.11(95% CI 2.06 – 8.19). Similarly WHR ≥ 0.84 is associated with increase in odds of IHD by a factor of 3.59 (95% CI 1.65 – 7.78). DISCUSSION Results of this study revealed that in Pakistani women aged 35 to 55 years none of the self-reported factors namely presence of family history of IHD, diabetes and hypertension turned out to be significant risk factors of IHD. Even though a greater percentage of women cases as compared to the controls in our research reported that they had a family history of IHD, and were diabetic and hypertensive. Our research findings are also contrary to the earlier reported empirical findings from many international as well as national studies. It has been documented that presence of family history of IHD, diabetes and hypertension are strongly associated with risk of IHD in men and women.20,21,22,23,24,25,26,27,28,29 Inconsistent findings of the current study with already available evidence can be attributed mainly to the fact that previously researchers have undertaken a sample of much older women. Women recruited in this study were comparatively younger, so the cardio protective role of endogenous estrogens in this age group cannot be ignored. Research evidence verifies that in pre-menopausal women aged 55 or fewer years, presence of endogenous estrogens tend to delay the risk of IHD by 10 to 20 years.30,31 In Pakistan the average age of menopause for Pakistani women is documented to be 44.5 year.32 However, the information regarding menopause status was not requested from women recruited in the current study. It is strongly suggested that in future, an inquiry into the menopausal status of women should be given due consideration while designing future studies. When an older sample size is recruited, advancing age increases chances of other risk factors of IHD. Research documents that individuals, who are older in age have greater chances of having co-morbidity of multiple risk factors of IHD like hypertension, hyperlipidaemia and diabetes.33 and hence are at a greater risk of IHD. Moreover, mostly younger and middle aged Pakistani population suffers from mild to moderate degrees of hypertension and diabetes as compared to uncontrollable and severe forms that is more prevalent among older Pakistani population,34. Uncontrollable and severe forms of diabetes and hypertension in comparatively older population has been found to be associated with risk of IHD35. However, in the current study, information pertaining to the use of medication for control of BP as well as diabetes was not gathered. Globally, three measures of obesity: waist circumference, WHR, and BMI,  are found to be significant predictors of IHD.36,37 Mostly, earlier studies have taken into account  one to two measures of obesity.  Those measures determined their association with the risk of IH.38.The current study has an edge over other studies as it has included all three measures of obesity with an objective to identify the most significant gender-based measures of obesity associated with the risk of IHD in Pakistani women. BMI ≥ 25 kg/m2 turned to be the most significant predictor of IHD in women. This finding is consistent with much of the previous empirical research literature, obesity as assessed by BMI has been found to be associated with the risk of IHD in both men and women.39,40 The Interheart study conducted in 52 countries including Pakistan and many other South Asian countries also confirmed that central obesity (BMI) is a significant risk factor of AMI in Pakistani population. In the current study, WHR ≥ 0.84 in addition to BMI ≥ 25 kg/m2 was found to be a significant risk factor of IHD in women. Results of present study are consistent with the earlier findings where WHR has been documented as a dominant risk factor predicting CHD.41,42,43,44,45,46 Waist hip ratio, as well as waist circumference, has found to be a significant risk factor for IHD in women.47 CONCLUSION Our study indicates that majority of the risk factors of Ischemic Heart Disease in women are modifiable and preventable; control of IHD is quite possible. This study invites directions for future research on IHD, and can help in providing gender based guidelines for primary and secondary cardiac interventions for Pakistan women. ACKNOWLEDGEMENTS The authors would like to thank concerned authorities of Jinnah hospital, Mayo hospital, Combined Military Hospital, Punjab Institute of Cardiology and Gulab Devi hospital for providing permission to collect data. AUTHOR DISCLOSURE STATEMENT “No competing financial interests exist.”

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