Ten years risk assessment of Atherosclerotic cardiovascular disease using Astro-CHARM and Pooled Cohort Equation in a South Asian population

Background Atherosclerotic cardiovascular diseases (ASCVD) are on the rise in low and middle income countries attributed to modern sedentary lifestyle and dietary habits. This has led to need of assessment of the burden of at-risk population so that prevention measures can be developed. The objective of this study was to assess ten years risk assessment of ASCVD using Astro-CHARM and Pooled Cohort Equation (PCE) in a South Asian population. Methods A total of 386 residents of all six districts of Karachi with no ASCVD were enrolled in the study. The inclusion criteria consisted of age 40 years or above and either gender. Study participants were enrolled after obtaining informed written consent and those study participants who were found to have either congenital heart disease or valvular heart diseases or ischemic heart disease were excluded from the study based on initial screening. For the calculation of 10 years risk of ACVD based on Astro-CHARM and PCE, the variables were obtained including medical history and coronary artery calcium and C-reactive protein measurements. Results Mean estimated 10-year risk of fatal or non-fatal myocardial infarction or stroke as per the Astro-CHARM was 13.98±8.01%, while Mean estimated 10-year risk of fatal or non-fatal myocardial infarction or stroke as per the PCE was 22.26±14.01%. Based on Astro-CHARM, 11.14% of the study participants were labelled as having high risk, while PCE estimated 20.73% of study participants as having high risk of ASCVD.Conclusion Despite the fact that our findings showed substantial differences in ten-year risk of ASCVD between Astro-CHARM and PCE, both calculators can be used to develop a new population specific risk estimator for the South Asian population. Our study provides the first step towards developing a


Introduction
With the ever increasing global burden of atherosclerotic cardiovascular diseases (ACVD) the need to timely assess the risk of a cardiovascular events cannot be more emphasized (1)(2)(3)(4)(5). Once among the most common causes of death in high income countries only, ACVD has become the leading cause of morbidity and mortality in low and middle income countries as well owing to epidemiologic transition and changing population dynamics. This trend is more prominent in South Asian population where (ACVD) is the leading cause of death (6, 7).
A number of risk estimators have been developed to assess the risk of any cardiovascular event in at risk population. Astro-CHARM and Pooled Cohort Equation (PCE) has been much widely used worldwide however these estimators have been developed in the west and not much evidence is present that how accurately they estimate ACVD in South Asian population. (8,9). Tariq et al. (10) reported that Pakistani population showed to have higher risk of ASCVD compared to whites, blacks, and Hispanic and even South Asians living in USA. Another study conducted in similar population showed that the burden of premature myocardial infarction to be as high as 12% (11). In addition, another large multi-centric study from the Pakistan attempted to predict the risk of atherosclerotic cardiovascular disease in Pakistani population, however, included subject with already suffered from ASCVD This study, to the best of our knowledge attempted to estimate the ten year risk of ASCVD in general population without any history of ASCVD using both Astro-CHARM and PCE, and compared the estimated risks using both.

Methods
This analytical cross-sectional study was conducted among three hundred and eighty-six of all six districts of Karachi who had no prior history of atherosclerotic cardiovascular disease including stroke. The selection of the study participants were done through snowball sampling. The inclusion criteria consisted of age 40 years of above and either gender. Study participants were enrolled after obtaining informed written consent and those study participants who were found to have either congenital heart disease or valular heart diseases or ischemic heart disease were excluded from the study based on initial screening.
Continuous data was assessed for normality based on visual inspection in order to apply parametric tests for comparisons. For the calculation of 10 years risk of ACVD based on Astro-CHARM and PCE, the variables were obtained in the following manner. Diabetes mellitus, hypertension, current smoking, and family history of heart attack were defined as per Astro-CHARM definitions (8).
Data were entered using MS Excel for Windows and analyses were done using STATA 11.0 while 10 years risk of ACVD was calculated using Astro-CHARM and PCE using the online calculators available at www.AstroCHARM.org and www.clincalc.com respectively. Participants were stratified as low-risk and high-risk individuals based on cut-off have of ≥ 7.5% for both Astro-CHARM and PCE.
Descriptive analyses were conducted by calculating the mean and standard deviation for all continuous variables while frequency and percentages were calculated for all categorical variables. Risk of ACVD was reported using both equations for combined study population and were also stratified for different subgroups.

Results
Mean age of the study participants was 49±7.10 years with 54% Males. Mean BMI was 28.11±5.38 while 45.6%, 15.8% and 14.2% were hypertensives, diabetics and current smokers respectively. Six (two percent) of the study participants had all three co-morbid conditions.Thirty percent had positive family history of MI. Mean CAC was 7.50±14.05 Agatston.
Mean estimated 10-year risk of fatal or non-fatal myocardial infarction or stroke as per the Astro-CHARM was 13.98±8.01%, while Mean estimated 10-year risk of fatal or non-fatal myocardial infarction or stroke as per the PCE was 22.26±14.01% shown in Figures 1 and 2. Risk comparison in different age categories showed significantly higher risk of ACVD in age groups of 55-60 years and 60 years and above compared to the ASCVD risk in the age group 40-45 years as calculated per Astro-CHARM. Table 1 shows the post-hoc comparisons of risk between different age groups as per Astro-CHARM. Figure

Discussion
To the best of our knowledge, current study reports ten year risk of ASCVD among non-cardiac Pakistani population using both Astro-CHARM and PCE and the comparison of the two calculators for the first time. In concordance with the findings of other studies, PCE overestimated the risk of ASCVD in the study population almost twice as that estimated by Astro-CHARM. Astro-CHARM which also includes indicators like coronary artery calcium and C-reactive protein during ASCVD risk assessment, these indicators are not readily available in low and middleincome countries therefore the significance of PCE cannot be neglected (13).
One of the key findings of this study was that both coronary artery calcium and C reactive protein significantly correlated with the risk scores generated by both Astro-CHARM and PCE which is in concordance with findings from other studies (14, 15). Especially in the case of CAC, a relatively recent study by JJ Carr et al (14) reported its effect on the risk of ASCVD among individuals well below 40 years of age. Keeping in mind that said study was conducted among African-Americans and Caucasians, who are relatively at lower risk of developing ASCVD compare to South Asians, it points towards a major limitation of these risk calculators among South Asians, who, in clinical experience suffer cardiac events at an even younger age (16) and evidenced by previous study from Pakistan (10), there is a dire need of development of population specific risk estimator for the South Asian population.
This study provided the grounds towards developing such risk estimator as well as initial step towards developing evidence-based decision making for primary prevention guidelines of atherosclerotic cardiovascular disease in this population.
Considering the fact that the population of South Asian countries consist of multiethnical groups with possibly different inherent risk of developing ASVD, as well as the absence of risk estimators in population below 40 years of age much evidence is required to develop population specific risk estimators and risk guided decision making tools for primary prevention among South Asians using robust study designs. Furthemore, considering the sub-optimal healthcare systems and absence of expensive investigating facilities like CAC in low and middle income countries of South Asia, development of risk estimators for these population also require large population based, ethnicity and age specific data to develop such a tool using both Astro-CHARM and PCE. Low and middle income countries are now overburdened with interventional procedures like angioplasty, and expensive methods of secondary prevention. Accurate risk assessment is the only solution in such resource poor settings where primary prevention can be implicated through lifestyle modifications and statins among high risk individuals.

CONCLUSION
Despite the fact that our findings showed substantial differences in ten-year risk of ASCVD between Astro-CHARM and PCE, both calculators can be used to develop a new population and specific risk estimators for the South Asian population. Our study provides the first step towards developing a risk assessment guided decision making protocol for primary prevention of ASCVD for South Asian population.

STRENGTHS AND LIMITATIONS:
The biggest strength of the study is the use and comparison of both ASCVD estimators in non-cardiac Pakistani general population selected from the largest city of the country with diverse population sub-groups from entire country thus providing data facsimile to general population of Pakistan.
Major limitation of the study is lies in the study design where lack of prospective follow-up cannot ensure the accuracy of these estimates. Furthermore, the data was taken from urban setting and implications of the findings cannot be ascertained on rural population.

Ethics approval and consent to participate
The ethical approval for the study was obtained from the Ethical Review Committee of National Institute of Cardio-Vascular Diseases (NICVD), Karachi, Pakistan.

Consent for publication
The manuscript does not contain any individual's identifiable information or data