Sudeb , Kaushik , and Suhana: Prevalence of Novel Risk Factors in Patients of Acute Coronary Syndrome in Eastern India: A Detailed Analysis.

Introduction

On the verge of modern medicine many factors have been identified related to acute coronary syndrome. Among them certain factors are directly related to acute coronary syndrome and are targeted for prevention and treatment of the same. These factors called conventional risk factors, are Smoking, Hypertension, Hyperlipidemia, Insulin resistance and Diabetes, Physical inactivity, Obesity and Advancing age. The final common pathway relating these factors is coronary artery disease.

But the conventional risk factors hardly explain 50 percent of all ACS. For the rest it requires search for other factors called Novel risk factors such as hsCRP, Homocysteine, IL6, Soluble ICAM, P selectin, Lp(a), Serum uric acid level, Chronic low grade inflammations etc. C reactive protein composed of five 23kDa subunit, is circulating member of pentraxin family, a downstream member of inflammation has now emerged as a major cardiovascular risk marker1. When measured with high sensitivity assay (hsCRP) it strongly and independently predicts risk of MI, Stroke, Peripheral arterial disease and sudden cardiac death in apparently healthy individuals even when LDL- C, Plasminogen activator inhibitor-1 levels are low2. hsCRP levels <1, 1 to 3, and >3 mg/lit should be interpreted as lower, moderate and higher relative vascular risk respectively when considered along with traditional markers of risk3. It also predicts risk with greatest usefulness for those at intermediate risk.

Homocysteine a sulfhydryl containing amino acid derived from demethylation of methionine. Mild to moderate elevation of homocysteine (plasma level >15 m mol/lit) is correlated with PVD, Carotid artery stenosis4, Coronary artery disease5,6. Homocysteine is directly toxic to endothelial cells7, and stimulate vascular smooth muscle cells8. It is also associated with venous thromboembolism9.

Lipoprotein(a) consists of an LDL particle with its apoB 100 linked by a disulfide bridge to apo (a), a variable length protein having sequence homology to plasminogen. Recent studies have suggested that Lp(a) bind and inactivate tissue factor pathway inhibitor and increase expression of plasminogen activator inhibitor and hence thrombosis. It may have local actions through oxidised phospholipid pathway10. Thus several mechanisms may contribute to a role of Lp(a) in atherothrombosis. Extremely high levels of Lp(a) (>65.6 mg/lit) are associated with increased cardiovascular risk independently11.

Serum uric acid level is now considered to be a predictor of acute coronary syndrome. It is associated with metabolic syndrome and thereby is a risk factor for coronary artery disease. A high baseline level of serum uric acid can independently predict future development of coronary artery disease12.

Aims and Objectives

  1. identify the novel risk factor(s) prevalent among the patients with ACS and having no or minimal conventional risk factors, admitted in our hospital.

  2. Measurement of serum level of known novel risk factors of target (uric acid, hsCRP, homocysteine, lipoproteine-a) by blood biochemistry.

  3. Screening of the individuals within the intermediate risk groups targeting the prevalent novel risk markers and provide specific measures against them.

  4. Obtaining important information regarding recurrence of ACS in those patient groups in long term follow up.

Materials and Methods

1. Study area

The study was carried out in the Department of General Medicine and Department of Cardiology, R G Kar Medical College & Hospital.

2. Study population

The patients suffering from acute coronary syndrome attending emergency and admitted in the indoor not having conventional risk factors for ACS.

3. Study period

One year.

4. Study design

It is a cross-sectional and observational hospital-based study.

5. Sample size

Total 70 patients (male 48, female 22) suffering ACS having no traditional risk factors were included.

6. Sampling technique

All patients admitted with ACS in the in-patient departments of Medicine and Cardiology during the study period were approached and those who met the inclusion criteria were included in the study.

7. Inclusion criteria

The patients of ages <75 for female and <65 for male suffering from ACS either for the first time or undergoing more than one episode.

8. Exclusion criteria

Patients suffering from ACS having any known conventional risk factors and any associated systemic illness leading to raised serum level of novel risk factors of interest. Patients of ACS having structural heart disease or not due to non-atherosclerotic cause.

9. Parameters to be used

  • Documentation of clinically diagnosed acute coronary syndrome patients.

  • Search for conventional risk factors by detailed history and blood biochemistry.

  • Then blood biochemical tests searching for novel factors done in those who had no conventional risk factors.

10. Statistical analysis

Data were analysed by epi-info 7.1.2.0, (CDC-ATLANTA), and are presented in simple Proportions. Chi square test were applied as test of significance for non parametric data. P value of <0.05 was considered to be significant.

Results & Analysis

Study revealed that majority of the study population belongs to 35 to 45 years age group (64%). Further analysis showed that 62.9% of them is above the age of forty years (Fig 1, Table 1).

68.6% of the patients were male whereas 31.4% were female. Comparison of age with sex showed 92.31% of patients below the age group of 40 years were male whereas only 7.69% were female in this age group. Above 40 years male and female were 54.55% and 45.55% respectively.

Only 7 (14.58%) of the male populations have normal biomarkers. Majority of them have combinations of risk biomarkers (Homocysteine, Lpa, hsCRP) (Table 2, Fig 2). Only 3 (13.63%) of the female populations have normal biomarkers. Majority of them have combinations of risk biomarkers (Homocysteine, Lpa, hsCRP) (Table 3, Fig 3).

Among the population under study 30 persons (42.86%) are having high serum homocysteine (>15) (Table 4, Fig 4). Out of 30 persons having elevated homocysteine 20 i.e. 66.67% are male. Among the male population with elevated homocysteine 14 (46.67%) are above age 40 and among females all (33.33%) are above 45 years. High homocysteine level is found to be more common among >40 years age group (54.55%) than among <40 years group (23.08%). This difference was found to be statistically significant [Chi-square= 6.608; P= 0.01]. There is no statistically significant difference found between high homocysteine levels of male and female [Chi square = 0.084, P=0.766].

Figure 1

Age distribution of the study population (N=70)

icfj.2015.4.14-g001.jpg

Figure 2

Showing prevalence of novel risk factors in male (N=48)

icfj.2015.4.14-g002.jpg

Figure 3

Showing prevalence of novel risk factors in female (N=22)

icfj.2015.4.14-g003.jpg

Figure 4

Showing age & sex distribution of homocysteine (N=30)

icfj.2015.4.14-g004.jpg

Figure 5

Age and sex distribution of high hsCRP (N=31)

icfj.2015.4.14-g005.jpg

Figure 6

Age and sex distribution of high Lp(a)

icfj.2015.4.14-g006.jpg

Figure 7

Age and sex distribution of high uric acid (N=23)

icfj.2015.4.14-g007.jpg

44.29% of the study population have high value of hsCRP (Table 5, Fig 5). Out of 31 persons having elevated hsCRP 21 i.e. 67.74% are male. Maximum number of high hsCRP found in the age group 40-44 years (41.94%). Among females high level of hsCRP is more prevalent above 45 years of age (12.9%). No significant difference in high level of hsCRP between two age groups were found. [Chi-square=0.065; P=0.79]. No statistically significant difference found between high hs-CRP levels in male and female.

41.43% of the study population have high Lp(a) level (Table 6, Fig 6). Among them 68.9% are males and 31.1% are females. Prevalence of Lp(a) increase with age in both males and females. Though high level of Lp(a) was found to be more among ≥40 years (50%) than among <40 years (26.92%), the difference was not found to be statistically significant [Chi square=3.587; P=0.058;OR=2.71 95% CI=0.95 – 7.7]. There is no statistically significant difference found between high Lp(a) levels of male and female.

Among the study population high value of uric acid is found in 32.86% population (Table 7, Fig 7). 69.57% of them are male and 30.43% are female. The prevalence of uric acid increases with age in both sexes. There is no statistically significant difference found between high uric acid levels of male and female.

Discussion

Cardiovascular death is the most common cause of mortality and morbidity both worldwide and in India13. Though nationwide exact data for occurrence of ACS not available in India, several epidemiologic studies from various parts indicates a rising trend in ACS14-16. India bears the highest burden of heart disease in the world. The disease also tends to be more aggressive and manifests at a younger age17.

Table 1

Age distribution of the study population (N = 70)

AGE GROUP(years) NUMBER %
30-34 7 10
35-39 18 27
40-44 27 37
45-49 9 13
50-54 9 13
TOTAL 70 100

Table 2

novel risk factors in the study population: male (n=48)

RISK FACTORS 30-34 YRS 35-39 YRS 40-44 YRS TOTAL
HsCRP 1 2 2 5
UA 1 3 2 6
HOMO C - 1 3 4
Lp (a) 1 1 2 4
hsCRP+ UA 1 3 2 6
HOMO C +Lp(a) - 2 4 6
HOMO C+ UA+ Lp(a) + hsCRP - 1 3 4
HOMO C+ Lp(a) + hsCRP - 2 4 6
NORMAL 3 2 2 7
TOTAL 7 17 24 48

Table 3

Novel risk factors in study population:female (n=22)

RISK FACTORS 35-39 YRS 40-44 YRS 45-49 YRS 50-54 YRS TOTAL
HsCRP 1 1 1 - 3
UA - - 1 1 2
HOMO C - - 1 2 3
Lp (a) - - 1 1 2
hsCRP+ UA - 1 1 - 2
HOMO C +Lp(a) - - - 2 2
HOMO C+ UA+ Lp(a) + hsCRP - - 1 2 3
HOMO C+ Lp(a) + hsCRP - - 1 1 2
NORMAL - 1 1 1 3
TOTAL 1 3 8 10 22

Table 4

Age and sex distribution of homocysteine (N=30)

AGE (years) MALE(%) FEMALE(%) TOTAL
30-34 - - -
35-39 6(20) - 6
40-44 14(46.67) - 14
45-49 - 3(10) 3
50-54 - 7(23.33) 7
TOTAL 20(66.67) 10(33.33) 30

Table 5

Age and sex distribution of high hsCRP (N=31)

AGE (years) MALE(%) FEMALE(%) TOTAL(%)
30-39 10(32.26) 1(3.22) 11
40-44 11(35.48) 2(6.45) 3
45-49 0 4(12.9) 4
50-54 0 3(9.68) 3
TOTAL 21(67.74) 10(32.26) 31(100)

Table 6

Age and sex distribution of high Lp(a)

AGE (years) MALE FEMALE TOTAL
30-34 1 - 1
35-39 6 - 6
40-44 13 - 13
45-49 - 3 3
50-54 - 6 6
Total 20 9 29

Table 7

Age and sex distribution of high uric acid (N=23)

AGE (years) MALE FEMALE TOTAL
30-34 2 0 2
35-39 7 0 7
40-44 7 1 8
45-49 0 3 3
50-54 0 3 3
TOTAL 16 7 23

In our study we have found that majority of the study population belongs to 35-45 years of age group (64%), which contrasts several previous studies of higher peak age (>50 yrs) including CREATE study18. A large number of patients below 40 yrs are male indicates male are more prone to develop ACS in younger age group. Where as in female peak incidence rate is in the age group of 45-49 years, indicating later onset of ACS compared to male counterpart.

Among the novel risk factors highest prevalence was found with hs CRP. 44.29% of the study population have high values of hs-CRP (67.74% are males 32.26% female) and 77.42% are in the age group less than 44 years (of which 35.48% are in the age group of 30-39 years, and 41.94% are in the age group of 40-45 years). High hsCRP value more in younger age group explains occurrence of high premature Coronary Artery Disease in our study and so in India19. So screening of population in the younger age group for high hs-CRP may be very useful as targeting those with statin therapy can reduce the mortality, morbidity and overall burden of health care20.

High value of homocysteine present in 30 persons i.e. 42.86%. It is found to be more associated in >40 years age group (54.55%) than among <40 years age group (23.08%). This difference was found to be statistically significant. So it may be used as screening method in >40 yrs of age both in male and female for ACS and targeted therapy with vitamin B12, folic acid may be considered in selected individuals21. Among the different sexes apparently males have higher homocysteine level compared to females but the difference is not statistically significant: this may be due to over all higher male population in the study group. In the female populations those in the peri-menopausal and post menopausal age have higher occurrence of high homocysteine level. Larger case control study is needed to establish the association of menopause with high homocysteine level and occurrence of acute coronary events.

High level of Lp(a) was found only 26.62% of younger patients (<40 yrs) .Therefore it will not be very sensitive as a screening method for ACS in younger individuals.

High level of uric acid was found in more than 1/3rd cases of ACS. Further quantitative controlled studies are required for determination of exact intervention level of uric acid level in blood to decrease the burden of ACS in younger individuals.

Conclusion

Incidence of Acute Coronary Syndrome in younger individuals in India has been increasing in alarming proportions. Measurements of hs CRP may be quite useful as screening method among all other parameters in those population and will help to decrease the burden of health care overall.

Statement of ethical publishing

The authors state that they abide by the statement of ethical publishing of the International Cardiovascular Forum Journal22.

Disclosure:

Authors have nothing to disclose.

Conflict of Interest:

There is no conflict of interest of any kind.

Fund Support:

There is no sponsor or funding support of any kind.

Guarantor of Submission:

The corresponding author is the guarantor of submission.

Acknowledgements

Authors acknowledged to all patients who gave their consent and participated in the study.

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Copyright (c) 2015 Sudeb Mukherjee, Kaushik Manna, Suhana Datta

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