The Open Cardiovascular Medicine Journal




ISSN: 1874-1924 ― Volume 13, 2019
REVIEW ARTICLE

Risk Factor Patterns for Premature Versus Late-Onset Coronary Artery Disease in Iran: A Systematic Review and Meta-Analysis



Negar Morovatdar1, Yones Bondarsahebi2, Nastaran Khorrampazhouh2, Seyyed A. Hozhabrossadati2, Konstantinos Tsarouhas3, Ramin Rezaee1, Reza J. Esfehani4, Hoorak Poorzand5, *, Amirhossein Sahebkar6, 7, 8, *
1 Clinical Research Unit, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
2 Students research committee, Faculty of medicine, Mashhad University of medical sciences, Mashhad, Iran
3 Department of Cardiology, University Hospital of Larissa, Larissa, Greece
4 Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
5 Atherosclerosis Prevention Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
6 Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
7 Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
8 School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Background:

There are few data regarding the risk factors of premature vs late-onset Coronary Artery Disease (CAD). This study systematically reviews these risk factors in Iranian people.

Methods:

Medline, Web of Science, Embase and SID (Scientific Information Database; www.sid.ir) databases were searched for studies comparing CAD risk factors in young and older patients in Iran. Data extracted and pooled odds ratio (OR) with 95% Confidence Interval (CI) for each risk factor were calculated. Publication bias was evaluated by Egger’s test.

Results:

Seven studies (9080 participants) were included in the meta-analysis; analysis was carried out independently for each risk factor. Smoking (Odds Ratio (OR): 2.57, 95% CI: 1.96-3.37; p=<0.001), family history of CAD (OR: 2.45: 95% CI, 1.44-4.15, p<0.001), opium abuse (OR: 2.44: 95% CI, 1.22-4.88; p=0.001) and hyperlipidaemia (OR: 1.4: 95% CI, 1.13-1.73; p=0.001) were more common in premature CAD compared with older CAD patients. In contrast, diabetes mellitus (OR: 0.54: 95% CI, 0.39-0.73; p=0.0001) and hypertension (OR: 0.36, 95% CI: 0.21-0.59; p<0.001) were less prevalent.

Conclusion:

Risk factors were significantly different between premature and late-onset CAD. Policies regarding smoking and opium cessation and controlling hyperlipidaemia may be useful for the prevention of premature CAD in Iran.

Keywords: Coronary artery disease, Premature, Cardiovascular risk factors, Hypertension, Hyperlipidaemia, Diabetees mellitus.


Article Information


Identifiers and Pagination:

Year: 2019
Volume: 13
First Page: 5
Last Page: 12
Publisher Id: TOCMJ-13-5
DOI: 10.2174/1874192401913010005

Article History:

Received Date: 29/11/2018
Revision Received Date: 07/01/2019
Acceptance Date: 28/01/2019
Electronic publication date: 26/03/2019
Collection year: 2019

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© 2019 Morovatdar et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


* Address correspondence to this author at the Atherosclerosis Prevention Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Neurogenic Inflammation Research Center Mashhad University of Medical Sciences, Mashhad, Iran; Tel: 985118002288; Fax: 985118002287; E-mail: sahebkara@mums.ac.ir, poorzandh@mums.ac.ir




1. INTRODUCTION

Although the elderly comprise the majority of patients with Coronary Artery Disease (CAD), the proportion of young patients presenting premature CAD is growing [1Reibis R, Treszl A, Wegscheider K, Bestehorn K, Karmann B, Völler H. Disparity in risk factor pattern in premature versus late-onset coronary artery disease: a survey of 15,381 patients. Vasc Health Risk Manag 2012; 8: 473-81.[http://dx.doi.org/10.2147/VHRM.S33305] [PMID: 22930639] ]. Young adults may be neglected in cardiovascular (CV) research. This growing group is exposed to various CAD risk factors [2Andersson C, Vasan RS. Epidemiology of cardiovascular disease in young individuals. Nat Rev Cardiol 2018; 15(4): 230-40.[http://dx.doi.org/10.1038/nrcardio.2017.154] [PMID: 29022571] ]. Unhealthy diet, obesity, smoking and illegal drug use are factors that should be confronted [3Fuster V, Mearns BM. The CVD paradox: mortality vs prevalence. Nat Rev Cardiol 2009; 6(11): 669.[http://dx.doi.org/10.1038/nrcardio.2009.187] [PMID: 19851344] ]. Since different CV risk factors patterns exist for premature and elderly groups [4Khot UN, Khot MB, Bajzer CT, et al. Prevalence of conventional risk factors in patients with coronary heart disease. JAMA 2003; 290(7): 898-904.[http://dx.doi.org/10.1001/jama.290.7.898] [PMID: 12928466] ], recognition of such patterns in youths is important and could improve public health management. It was reported that arterial hypertension, abdominal circumference and sedentary life style are becoming more prevalent among elders [5Diniz MA. Tavares DMdS. Risk factors for cardiovascular diseases in aged individuals in a city in the state of Minas Gerais. Texto Contexto Enferm 2013; 22: 885-92.[http://dx.doi.org/10.1590/S0104-07072013000400003] ]. Considering the high prevalence of CV disease (CVD) among Iranians and in order to provide a clearer picture for healthcare managers /policy makers, we compared the prevalence of different CV risk factors in young and older Iranian patients diagnosed with CAD.

2. METHODS

The scientific databases Medline, Web of Science, Embase and SID (Scientific Information Database; www.sid.ir) were systematically searched until October 28, 2017 using the following key terms: coronary disease, coronary artery disease, coronary heart disease, vascular disease, atherosclerosis, arteriosclerosis, risk factors, population at risk and IRAN see Table 1. All retrieved articles were independently checked by 2 reviewers. Articles were checked for title and abstract in a first round. Then, full-text checking was carried out for papers chosen during the first step.

2.1. Inclusion Criteria

Studies that compared risk factors of CAD in young and elderly Iranian patients were included in the present article Table 2. Letters to editors, duplicated articles, congress abstracts and reviews were excluded.

2.2. Data Extraction and Quality Assessment

The following data were extracted by 4 independent reviewers: first author name, year, study population size and age (years), study design, diagnosis criteria of CAD as well as risk factors including smoking, hypertension, diabetes mellitus, opium abuse, family history of CAD, obesity, hyperlipidaemia and lipid profile. Risk factors extracted from the retrieved papers (proportion of patients have/have not a risk factor in young and elder groups in each study for dichotomous variables as smoking, hypertension, diabetes mellitus, opium abuse, family history of CAD, hyperlipidaemia and mean and number of each groups for quantitative variables as lipid profile and body mass index) included in our meta-analysis are reported in Table 3. In this study, we used Joanna Briggs Institute Critical Appraisal Checklist to evaluate the quality of case control, cross-sectional and cohort studies. Each retrieved article was independently evaluated by 2 reviewers using the above noted checklist and a joint decision was made for inclusion/exclusion of each article. In case a joint decision could not be achieved, a third reviewer checked the article.

2.3. Statistical Analysis

STATA ver.11 was used to analyse data for each risk factor. The Odds Ratio (OR) with 95% Confidence Interval (CI) was calculated for each risk factor and results from the selected studies concerning the risk factors hyperlipidaemia were analysed using the fixed effects model, while the random-effects model (DerSimonian and Laird method) was used for analysing results on diabetes mellitus, smoking, hypertension, family history and opium abuse. Study heterogeneity was evaluated by I2 (an estimate of the variance across studies caused by heterogeneity rather than chance). Sensitivity analysis was carried out to assess the robustness of pooled estimates if appropriate [6Sahebkar A. Does PPARγ2 gene Pro12Ala polymorphism affect nonalcoholic fatty liver disease risk? Evidence from a meta-analysis. DNA Cell Biol 2013; 32(4): 188-98.[http://dx.doi.org/10.1089/dna.2012.1947] [PMID: 23448101] , 7Serban C, Sahebkar A, Ursoniu S, et al. A systematic review and meta-analysis of the effect of statins on plasma asymmetric dimethylarginine concentrations. Sci Rep 2015; 5: 9902.[http://dx.doi.org/10.1038/srep09902] [PMID: 25970700] ]. Publication bias was assessed by Egger test.

3. RESULTS

3.1. Study Characteristics

Searching Medline, Web of Science, Embase and SID databases yielded 2866 potential papers, of which, 10 papers were eligible for meta-analysis. However, risk factors that were discussed only by 1 study were not included in the meta-analysis. Finally, meta-analysis was performed for 7 studies including cross sectional [8Hosseini SK, Soleimani A, Salarifar M, et al. Demographics and angiographic findings in patients under 35 years of age with acute ST elevation myocardial infarction. J Tehran Heart Cent 2011; 6(2): 62-7.[PMID: 23074607] -11Soleimani Eslami A, Dastgiri S, Yaghoubi A, et al. Risk factors of coronary artery disease in patients less and higher than 45 years. J Sch Public Health Inst Public Health Res 2010; 9: 13-22.], case control [12Vaisi-Raygani A, Ghaneialvar H, Rahimi Z, et al. The angiotensin converting enzyme D allele is an independent risk factor for early onset coronary artery disease. Clin Biochem 2010; 43(15): 1189-94.[http://dx.doi.org/10.1016/j.clinbiochem.2010.07.010] [PMID: 2065 5894] ] and cohort studies [13Sadrbafghi M, Rafiee M, Namayandeh M, et al. Premature myocardial infarction in Yazd. Tehran Univ Med J 2005; 7: 579-89., 14Hadaegh F, Mohebi R, Khalili D, Hasheminia M, Sheikholeslami F, Azizi F. High normal blood pressure is an independent risk factor for cardiovascular disease among middle-aged but not in elderly populations: 9-year results of a population-based study. J Hum Hypertens 2013; 27(1): 18-23.[http://dx.doi.org/10.1038/jhh.2011.112] [PMID: 22217674] ], with 9080 subjects (Fig. 1). Meta-analysis was separately carried out for each risk factor of premature CAD according to data reported in papers and 3 to 6 papers were included in meta- analysis for each risk factor depending on the reported data. Table 1 demonstrates qualitative reports of studies eligible for meta-analysis.

The definition of young and elderly CAD varied among studies; 1 study considered those aged <50 years for men and 55 years for women as “young” [13Sadrbafghi M, Rafiee M, Namayandeh M, et al. Premature myocardial infarction in Yazd. Tehran Univ Med J 2005; 7: 579-89.]; others considered 35 [8Hosseini SK, Soleimani A, Salarifar M, et al. Demographics and angiographic findings in patients under 35 years of age with acute ST elevation myocardial infarction. J Tehran Heart Cent 2011; 6(2): 62-7.[PMID: 23074607] ], 45 [15Mirzaiee M, Rahnama A, Esmailian F, Bakhshi H. Lipoprotein a (LPa) in young patients with myocardial infarction. Rafsanjan Univ Med Sci J 2013; 12(8)], 50 [9Mahmoodi MR, Abadi AR, Kimiagar SM. Sex differences in myocardial infarction events between patients with and without conventional risk factors: the Modares Heart Study. Am Heart Hosp J 2007; 5(4): 228-35.[http://dx.doi.org/10.1111/j.1541-9215.2007.07301.x] [PMID: 17982303] ], 55 [12Vaisi-Raygani A, Ghaneialvar H, Rahimi Z, et al. The angiotensin converting enzyme D allele is an independent risk factor for early onset coronary artery disease. Clin Biochem 2010; 43(15): 1189-94.[http://dx.doi.org/10.1016/j.clinbiochem.2010.07.010] [PMID: 2065 5894] ], 60 [14Hadaegh F, Mohebi R, Khalili D, Hasheminia M, Sheikholeslami F, Azizi F. High normal blood pressure is an independent risk factor for cardiovascular disease among middle-aged but not in elderly populations: 9-year results of a population-based study. J Hum Hypertens 2013; 27(1): 18-23.[http://dx.doi.org/10.1038/jhh.2011.112] [PMID: 22217674] ] and, 45 years old as “young” and >65 years old as “older” [10Safaei N, Alikhah H, Abadan Y. Coronary risk factors in patients underwent coronary artery bypass grafting. Pak J Biol Sci 2011; 14(1): 25-33.[http://dx.doi.org/10.3923/pjbs.2011.25.33] [PMID: 21913494] ].

3.2. Smoking

Six studies investigated the association between smoking and CAD in young and elderly patients. In young patients, smoking was associated with a higher risk of CAD compared with elderly CAD patients (OR: 2.57: 95% CI, 1.96-3.37; p≤0.001), with a heterogeneity of I2=69.1% among the studies (p=0.006) (Fig. 2). Sensitivity analysis did not affect the results. No publication bias was found in the evaluated articles (Egger test, p=0.5).

3.3. Diabetes Mellitus

Six studies investigated the association between diabetes mellitus and CAD in young and elderly patients. Diabetes mellitus was associated with a lower risk of CAD in young patients compared with elderly patients (OR: 0.54: 95% CI, 0.39-0.73; p<0.001). Statistically significant heterogeneity was found among the studies (I2= 71.35%; p=0.0.004) (Fig. 3) and no publication bias was seen (Egger test, p=0.05). In sensitivity analysis after deletion of one study [13Sadrbafghi M, Rafiee M, Namayandeh M, et al. Premature myocardial infarction in Yazd. Tehran Univ Med J 2005; 7: 579-89.] the result did not have heterogeneity.

3.4. Hyperlipidaemia

Three studies compared the frequency of hyperlipidaemia in young and elder CAD patients. Hyperlipidaemia was associated with a higher risk of CAD in young patients compared with elderly patients (OR: 1.4: 95% CI, 1.13-1.73; p=0.002). No statistically significant heterogeneity was found among the studies (I2= 0%; p= 0.7) (Fig. 4) and no publication bias was detected (Egger test, p=0.2).

Table 1
Search strategy.


Table 2
Baseline characteristics of all the studies included in the meta-analysis.


Table 3
Risk factor definition in papers included in meta-analysis.


Fig. (1)
Flow diagram of study.


Fig. (2)
Forest plots of odd ratios for association between smoking and premature coronary artery disease (CAD) vs late-onset CAD.


Fig. (3)
Forest plots of odd ratios for association between diabetes mellitus and premature Coronary Artery Disease (CAD) vs late-onset CAD.


Fig. (4)
Forest plots of odd ratios for association between hyperlipidaemia and premature Coronary Artery Disease (CAD) vs late-onset CAD.


3.5. Hypertension

Six studies compared the frequency of hypertension between young and elder CAD patients. Hypertension was associated with a lower risk of CAD in young patients compared with elderly patients (OR: 0.36: 95% CI=0.21-0.59; p<0.001). Significant heterogeneity was detected among the studies (I2=89%; p<0.001) (Fig. 5). In sensitivity analysis, exclusion of the Vaisi-Raygan study, showed that the remaining studies were homogenous (OR=0.45: 95% CI=0.4-0.51; p<0.001). No publication bias was found (Egger test, p=0.66)

3.6. Family History of CAD

Five studies investigated the association between family history and CAD in young and elderly patients. Family history of CAD was significantly associated with a higher risk of CAD in young patients compared with older subjects (OR: 2.45: 95% CI, 1.44 -4.15; p<0.001). A significant heterogeneity was found among the studies (I2=84%; p<0.0001) (Fig. 6). In sensitivity analysis, following exclusion of the Safaiee et al. study, studies were found to be homogenous (OR: 1.91, 95% CI= 1.37-2.66, p<0.001 and I2=53%, p=0.08) which might be due to large difference between the “age cut-off” considered by Safaiee et al. for young (i.e. <45 years old) and older patients (>65 years old). No publication bias was found (Egger test, p=0.5).

3.7. Opium Abuse

Three studies investigated the association between opium abuse and premature CAD and late onset CAD. Opium abuse was associated with higher risk of premature CAD compared with late onset CAD (OR: 2.44: 95% CI=1.22-4.88; p=0.01). A significant heterogeneity was found among the studies (I2= 80.2%; p=0.006) (Fig. 7). No publication bias was detected (Egger test, p=0.7).

Fig. (5)
Forest plots of odd ratios for association between hypertension and premature coronary artery disease (CAD) vs late-onset CAD.


Fig. (6)
Forest plots of odd ratios for association between family history of CAD and premature coronary artery disease (CAD) vs late-onset CAD.


Fig. (7)
Forest plots of odd ratios for association between opium abuse and premature Coronary Artery Disease (CAD) vs late-onset CAD.


4. DISCUSSION

In this systematic review and meta-analysis, the prevalence of certain CV risk factors varied significantly between Iranian patients with premature and late-onset CAD. Opium abuse, smoking, hyperlipidaemia and family history of CAD are more frequent in premature CAD compared with late-onset CAD; however, diabetes mellitus and hypertension were more frequent in late-onset CAD.

Similar to other studies, we found that smoking was more prevalent in premature CAD compared with late-onset disease [1Reibis R, Treszl A, Wegscheider K, Bestehorn K, Karmann B, Völler H. Disparity in risk factor pattern in premature versus late-onset coronary artery disease: a survey of 15,381 patients. Vasc Health Risk Manag 2012; 8: 473-81.[http://dx.doi.org/10.2147/VHRM.S33305] [PMID: 22930639] , 16Rathod KS, Jones DA, Gallagher S, et al. Atypical risk factor profile and excellent long-term outcomes of young patients treated with primary percutaneous coronary intervention for ST elevation myocardial infarction. Eur Heart J Acute Cardiovasc Care 2016; 5(1): 23-32.[http://dx.doi.org/10.1177/2048872614567453] [PMID: 25589633] , 17Schoenenberger AW, Radovanovic D, Stauffer JC, et al. Acute coronary syndromes in young patients: presentation, treatment and outcome. Int J Cardiol 2011; 148(3): 300-4.[http://dx.doi.org/10.1016/j.ijcard.2009.11.009] [PMID: 19942306] ]. Smoking initiates/promotes atherosclerosis by altering cardiac haemodynamics, dyslipidaemia and increased free oxygen radicals [17Schoenenberger AW, Radovanovic D, Stauffer JC, et al. Acute coronary syndromes in young patients: presentation, treatment and outcome. Int J Cardiol 2011; 148(3): 300-4.[http://dx.doi.org/10.1016/j.ijcard.2009.11.009] [PMID: 19942306] ]. Smoking is associated with lower High Density Lipoprotein Cholesterol (HDL-C) levels, higher triglycerides, unfavourable changes in apolipoprotein (apo) A1 and B, and in lipoprotein particle size [18Slagter SN, van Vliet-Ostaptchouk JV, Vonk JM, et al. Associations between smoking, components of metabolic syndrome and lipoprotein particle size. BMC Med 2013; 11: 195.[http://dx.doi.org/10.1186/1741-7015-11-195] [PMID: 24228807] ]; the apoB/apo A ratio predicts CV events [19Tamang HK, Timilsina U, Singh KP, et al. Apo B/Apo AI ratio is statistically a better predictor of cardiovascular disease (CVD) than conventional lipid profile: a study from Kathmandu Valley, Nepal. J Clin Diagn Res 2014; 8(2): 34-6.[PMID: 24701475] ]. Compared with non-smokers, cigarette smoking was found to be associated with an average lifetime loss of 10 years [20Doll R, Peto R, Boreham J, Sutherland I. Mortality in relation to smoking: 50 years’ observations on male British doctors. BMJ 2004; 328(7455): 1519.[http://dx.doi.org/10.1136/bmj.38142.554479.AE] [PMID: 15213107] ]. One year after the implementation of smoking restriction in public and hospitality sectors in Germany, a decline of 13.3 and 8.6% in angina pectoris and myocardial infarction, respectively, was reported [21Sargent JD, Demidenko E, Malenka DJ, Li Z, Gohlke H, Hanewinkel R. Smoking restrictions and hospitalization for acute coronary events in Germany. Clin Res Cardiol 2012; 101(3): 227-35.[http://dx.doi.org/10.1007/s00392-011-0385-1] [PMID: 22350716] ]. Thus, smoking cessation and strategies to prevent smoking relapse should be considered.

We found that the prevalence of opium abuse is significantly higher in young CAD patients compared with older subjects with CAD. Although our analysis showed a significant association between smoking and opium abuse with higher CAD risk in young adults, it should be noted that the vast majority of opium abusers are also cigarette smokers. Nonetheless, Masoomi et al. reported that opium abuse was recognized as a CAD risk factor in non-smokers after adjusting for other CAD risk factors [22Masoomi M, Ramezani MA, Karimzadeh H. The relationship of opium addiction with coronary artery disease. Int J Prev Med 2010; 1(3): 182-6.[PMID: 21566789] ]. Prevention programs concerning smoking/illegal substance (e.g. opium) abuse should be planned for young Iranian adults and put into practice in order to minimize the risk such habits pose for CAD.

Our meta-analysis showed that hyperlipidaemia is more prevalent in young CAD patients compared with older patients. However, studies are not consistent in this regard as some studies reported that dyslipidaemia is more prevalent in young patients [23Das PK, Kamal SM, Murshed M. Acute myocardial infarction in young Bangladeshis: A comparison with older patients. J Indian Coll Cardiol 2015; 5: 20-4.[http://dx.doi.org/10.1016/j.jicc.2014.10.003] , 24Ge J. Acute myocardial infarction in young adults: risk factors, clinical features and management strategies. Cardiol Plus 2017; 2: 1.] while others showed that it is more prevalent in older patients with CAD [25Obaya M, Yehia M, Hamed L, Fattah AA. Comparative study between elderly and younger patients with acute coronary syndrome. Egyptian J Critical Care M 2015; 3: 69-75.[http://dx.doi.org/10.1016/j.ejccm.2015.12.002] -27Ricci B, Cenko E, Vasiljevic Z, et al. Acute Coronary Syndrome: The Risk to Young Women. J Am Heart Assoc 2017; 6(12): e007519.[http://dx.doi.org/10.1161/JAHA.117.007519] [PMID: 29273636] ].

We found that family history of CAD in premature CAD is twice as prevalent as that in late-onset CAD. Andresdottir et al. [28Andresdottir MB, Sigurdsson G, Sigvaldason H, Gudnason V. Fifteen percent of myocardial infarctions and coronary revascularizations explained by family history unrelated to conventional risk factors. The Reykjavik Cohort Study. Eur Heart J 2002; 23(21): 1655-63.[http://dx.doi.org/10.1053/euhj.2002.3235] [PMID: 12398822] ] reported that regardless of cholesterol levels, obesity and hypertension, up to 16.6% of CAD cases are attributable to CAD family history. Women with a history of premature maternal infarction younger than 50 years, showed up to 2.57 fold increased risk of CAD compared with women without such history [29Sesso HD, Lee I-M, Gaziano JM, Rexrode KM, Glynn RJ, Buring JE. Maternal and paternal history of myocardial infarction and risk of cardiovascular disease in men and women. Circulation 2001; 104(4): 393-8.[http://dx.doi.org/10.1161/hc2901.093115] [PMID: 11468199] ]. Compared with older ST-segment elevation myocardial infarction (STEMI) patients, a family history of early CAD (OR=3.194) was significantly more associated with STEMI in young patients [30Yunyun W, Tong L, Yingwu L, et al. Analysis of risk factors of ST-segment elevation myocardial infarction in young patients. BMC Cardiovasc Disord 2014; 14: 179.[http://dx.doi.org/10.1186/1471-2261-14-179] [PMID: 25487289] ].

Similar to other studies, we found that diabetes mellitus prevalence increases with increasing age as diabetes mellitus was less frequent in young compared to older CAD patients [25Obaya M, Yehia M, Hamed L, Fattah AA. Comparative study between elderly and younger patients with acute coronary syndrome. Egyptian J Critical Care M 2015; 3: 69-75.[http://dx.doi.org/10.1016/j.ejccm.2015.12.002] , 26Matsis K, Holley A, Al-Sinan A, Matsis P, Larsen PD, Harding SA. Differing Clinical Characteristics Between Young and Older Patients Presenting with Myocardial Infarction. Heart Lung Circ 2017; 26(6): 566-71.[http://dx.doi.org/10.1016/j.hlc.2016.09.007] [PMID: 28089789] ]. Age-related risk factors, such as diabetes mellitus, are known to be more prevalent in older than younger patients. Risk factors for premature CAD between age- and sex-matched patients and healthy controls are studied elsewhere (data not published yet).

To the best of our knowledge, this study is the first systematic review with meta-analysis regarding CAD risk factors in young Iranian adults. The prevalence and the severity of the risk factors were compared with elder patients. Identification and ranking of prevalent risk factors especially in young adults is of importance for public health systems.

Special concern and attention has been placed by the authors on the low probability power of the Egger test in identifying publication bias in small numbers of studies included in a meta-analysis (current meta-analysis 3-6 studies). More specifically, the power of the Egger method to detect bias is low with small numbers of studies, while the Begg method makes fewer assumptions than the Egger test, but it is insensitive to other types of bias (type 1 and 2 error) to which the Egger test is sensitive [31Sterne JA, Egger M, Smith GD. Investigating and dealing with publication and other biases. Systematic reviews in health care: meta-analysis in context 2001; 189: 208.[http://dx.doi.org/10.1002/9780470693926.ch11] , 32Lin L. Bias caused by sampling error in meta-analysis with small sample sizes. PLoS One 2018; 13(9): e0204056.[http://dx.doi.org/10.1371/journal.pone.0204056] [PMID: 30212588] ]. In this meta-analysis all Egger test p values were higher than 0.1 (significant level) except for diabetes mellitus. Nevertheless, our results regarding publication bias are consistent with both tests. Another concern that exits is the competing risk of other risk factors that affect mortality rate at earlier age; in this regard, some patients may have died before becoming “elderly” due to various causes including CAD.

Since the definition of “Premature Coronary Artery Disease” was not consistent across studies, over/under-estimation may occur in pooled analysis of risk factors frequency. Preventive treatment was also not mentioned in all of studies.

CONCLUSION

Opium abuse, cigarette smoking, hyperlipidaemia and family history of CAD were more prevalent in young Iranian CAD patients compared with older ones. It is of crucial importance to conduct large cohort studies in order to establish vascular risk factor among different age groups.

SOURCE OF FUNDING

Mashhad University of Medical Sciences, Mashhad, Iran.

CONSENT FOR PUBLICATION

Not applicable.

CONFLICT OF INTEREST

The authors declare no conflict of interest, financial or otherwise.

ACKNOWLEDGEMENTS

Declared none.

REFERENCES

[1] Reibis R, Treszl A, Wegscheider K, Bestehorn K, Karmann B, Völler H. Disparity in risk factor pattern in premature versus late-onset coronary artery disease: a survey of 15,381 patients. Vasc Health Risk Manag 2012; 8: 473-81.[http://dx.doi.org/10.2147/VHRM.S33305] [PMID: 22930639]
[2] Andersson C, Vasan RS. Epidemiology of cardiovascular disease in young individuals. Nat Rev Cardiol 2018; 15(4): 230-40.[http://dx.doi.org/10.1038/nrcardio.2017.154] [PMID: 29022571]
[3] Fuster V, Mearns BM. The CVD paradox: mortality vs prevalence. Nat Rev Cardiol 2009; 6(11): 669.[http://dx.doi.org/10.1038/nrcardio.2009.187] [PMID: 19851344]
[4] Khot UN, Khot MB, Bajzer CT, et al. Prevalence of conventional risk factors in patients with coronary heart disease. JAMA 2003; 290(7): 898-904.[http://dx.doi.org/10.1001/jama.290.7.898] [PMID: 12928466]
[5] Diniz MA. Tavares DMdS. Risk factors for cardiovascular diseases in aged individuals in a city in the state of Minas Gerais. Texto Contexto Enferm 2013; 22: 885-92.[http://dx.doi.org/10.1590/S0104-07072013000400003]
[6] Sahebkar A. Does PPARγ2 gene Pro12Ala polymorphism affect nonalcoholic fatty liver disease risk? Evidence from a meta-analysis. DNA Cell Biol 2013; 32(4): 188-98.[http://dx.doi.org/10.1089/dna.2012.1947] [PMID: 23448101]
[7] Serban C, Sahebkar A, Ursoniu S, et al. A systematic review and meta-analysis of the effect of statins on plasma asymmetric dimethylarginine concentrations. Sci Rep 2015; 5: 9902.[http://dx.doi.org/10.1038/srep09902] [PMID: 25970700]
[8] Hosseini SK, Soleimani A, Salarifar M, et al. Demographics and angiographic findings in patients under 35 years of age with acute ST elevation myocardial infarction. J Tehran Heart Cent 2011; 6(2): 62-7.[PMID: 23074607]
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