Myocardial Infarction, Susceptibility to, 1

Alternative Names

  • MCI1
  • Myocardial Infarction, Early-Onset, Susceptibility to
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WHO-ICD-10 version:2010

Diseases of the circulatory system

Ischaemic heart diseases

OMIM Number

608446

Mode of Inheritance

N/A

Gene Map Locus

1p34, 1q25,6p12, 6q25.1,13q12.3

Description

Myocardial Infarction (MI), known in popular parlance as a heart attack, is a condition wherein a sudden blockage of a coronary artery leads to the death of cardiac muscle. The coronary arteries, which supply blood to the heart muscles, can get blocked due to the build-up of cholesterol within their walls in the form of plaques, also known as atherosclerosis. These plaques can rupture at times, forming a clot which can block the site of rupture, thereby blocking blood flow to the heart leading it to be deprived of oxygen. Irreversible death of the heart muscle begins to occur if oxygen supply is not restored to the heart within 20 to 40 minutes. With each passing minute, more and more heart tissue is deprived of blood and oxygen, and dies. At the end of a process of such tissue death lasting for 6-8 hours, a heart attack ensues. Typical symptoms of a heart attack include pain and a squeezing sensation of the chest, arm and upper back pain, head and tooth ache, shortness of breath, sweating, heartburn, nausea, and malaise. Unfortunately, a quarter of patients who experience an MI have a silent attack which shows none of these symptoms, and are thus, difficult to detect early.

MI is a significant health problem in developed countries, and is now becoming increasingly significant in the developing countries too. About 12 million people die each year worldwide due to cardiovascular diseases. The major risk factors for developing an MI are smoking, hypertension, hypercholesterolemia, lack of physical activity, obesity, diabetes, alcohol consumption, stress, and a family history of MI. In persons aged 40-70 years, male gender is also considered as a significant risk factor. However, studies now have also shown that women tend to have MIs with atypical symptoms. Additionally, the risk for women significantly increases after menopause.

It is important to call for medical assistance as soon as a suspicion of an MI is felt. Immediate coronary angiography, CT scan, echocardiography, and ECG tests can be done to diagnose the condition. Later, blood tests to measure the levels of Troponins, Creatinine phosphokinase, and/or serum myoglobin may also be conducted to confirm the diagnosis. Treatment is aimed at the immediate restoration of blood flow and stopping further damage of heart tissue. This may include the administration of medications, such as blood thinners, clot busters, pain relievers, and beta blockers, as well as surgery to restore blood flow, such as coronary angioplasty and stenting, or coronary artery bypass surgery.

Molecular Genetics

Various genome wide scans have been performed to understand the genetic susceptibility to myocardial infarction. These studies have identified several different loci, all in different populations. The earliest genes identified with susceptibility to MI include two genes in the leukotriene pathway, ALOX5AP (Arachidonate 5-Lipoxygenase-Activating Protein) and LTA4H (Leukotriene A4 Hydrolase), as well as the genes LTAR (Lymphotoxin-Alpha Receptor) and LGALS2 (Lectin, Galactoside-Binding, Soluble, 2). In the past year, a mutation in the LRP8 gene, which codes for the Apolipoprotein E Receptor-2 was found to be significantly associated with susceptibility to MI.

Epidemiology in the Arab World

View Map
Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
608446.G.1Lebanon Myocardial infarction; Coronary artery s...NR_003529.3:n.2698+1211A>G, NM_001242767.1:c.1260-4955G>ASaade et al. 2011 Study of 2002 Lebane...

Other Reports

Egypt

[See: Qatar > Chaikhouni et al., 1993; Kuwait > Olusi et al., 1999].

Jordan

[See: Kuwait > Al-Owaish et al., 1983; Olusi et al., 1999; Qatar > Chaikhouni et al., 1993;].

Kuwait

Al-Owaish (1983) carried out a retrospective study investigating the Kuwaiti data on acute myocardial infarction (AMI), collected from the two major general hospitals in Kuwait in 1978. The 428 cases included 133 Kuwaiti men and 23 Kuwaiti women. The Non-Kuwaiti patients included Jordanian-Palestinian patients. Age-specific incidence rates were found to increase with increasing age in both men and women. The incidence rates also increased with higher socio-economic status, although the incidence among lower-status Kuwaitis was significantly lower than that among lower-status Non-Kuwaitis. Among the patients, there was history of hypertension (22%), diabetes mellitus (30%), smoking (71%), and previous AMI (20%). The overall mortality rate was 16%. Older age, lower blood pressures, extensive anterior myocardial infarcts, and reduced serum cholesterol levels seemed to be associated with unfavorable prognosis.

Al-Muhtaseb et al. (1989) measured plasma and lipoprotein cholesterol, triglycerides, apolipoproteins (apo) A-I, A-II, B and phospholipid concentrations in 60 young Kuwaiti male myocardial infarction (MI) survivors under the age of 40 years. Controls in the study were matched for age, relative weights, smoking, dietary habits and physical activities. Results of this study showed that the size of apo C-III, B and A-I beside HDL2 cholesterol proved to be of prospective employment in distinguishing normal controls from MI patients. Later, Al-Muhtaseb and Al-Yousef (1992) studied lipid, lipoprotein and apolipoprotein profiles in 180 young survivors (ages 28 to 45-years) of myocardial infarction. The study also included 200 sex and age matched control subjects. The patients showed a significant increase in total cholesterol, LDL- and VLDL-cholesterol, triglycerides, apo-B, apo-CIII, and apo-E levels. Simultaneously, levels of HDL lipoprotein and cholesterol and apo-AI were found to be increased in the patients compared to the controls. No significant changes were detected in levels of HDL3 cholesterol, apo-AII, and apo CII.

Throughout the period of 1992 to 1994, Olusi et al. (1997) carried out a retrospective study and determined serum concentrations in Kuwaiti patients with confirmed diagnosis of myocardial infarction. The study demonstrated significant correlation among hypertriglyceridemia and hypoalbuminemia in Kuwaiti Arabs. Later, Olusi et al. (1999) carried out a retrospective study on a cohort of 250 cases of myocardial infarction (MI) and a control group of 600 apparently healthy individuals throughout the period of January 1992 and July 1995. The cohort consisted of 88 Kuwaiti Arabs, 97 non-Kuwaiti Arabs including Egyptians, Palestinians, Lebanese and Jordanians, while the rest comprised non-Arab South Asian patients. Male predominance was noticed throughout the study within all ethnic groups. The study also revealed that Arab and non-Arab South Asian MI patients suffered from significantly higher serum triglyceride and total bilirubin, but experienced lower serum total protein and albumin concentrations, than healthy controls.

At Al-Sabah Hospital in Kuwait, Al-Adsani et al. (2000) conducted a study on 126 acute myocardial infarction (AMI) patients to reveal the personal and clinical properties of cases, the prevalence of the main risk factors amongst subjects, and the factors correlated with in-hospital morbidity and mortality (using multiple logistic regression). The study consisted of 84.9% males. The patients' history of other illnesses included diabetes (44.4%), hypertension (29.6%), and CHD (16.8%). Al-Adsani et al. (2000) concluded that the load of AMI-related morbidity and mortality can be decreased through the management of smoking, early diagnosis and the suitable treatment of diabetes.

A retrospective study was conducted by Lasheen et al. (2006) to evaluate the changing trends in the management of acute myocardial infarction in Kuwait. The study involved the records of 2280 patients (85% male; average age: 54-years) diagnosed with AMI in the coronary care unit of a Kuwaiti hospital between 1998 and 2002. This patient population had a high prevalence of smoking (50%) and diabetes (39%). Thrombolytic therapy was administered to 62% of the patients; and the rate increased significantly over the five years. This rate of thrombolysis is exceedingly high, and reached up to 95% when patients not eligible for thrombolysis were excluded. This is one of the highest reported rates of thrombolysis. The mean time from the first diagnostic ECG to the start of thrombolytic treatment was found to be 90 minutes, and showed significant improvement over the study period. In large part, this improvement was attributed to a change of policy requiring administration of thrombolytic treatment in the emergency room. However, Lasheen et al. (2006) recommended further reduction in in-hospital delay by designing suitable emergency department triage protocols. Upon discharge, patients were found to have been given aspirin (94%), beta-blockers (82%), ACE inhibitors (43%), lipid lowering drugs (43%), and calcium channel antagonists (9%). In-hospital catheterizations significantly increased over the five-year study period, while no significant statistical difference was observed over the number of deaths in each year. [Lasheen I, Zubaid M, Suresh CG, Bader HES. Changing trends in the management of acute myocardial infarction: a five-year study. Kuwait Med J. 2006; 38(3):201-10.]

Zubaid et al. (2006) collected retrospective hospital data from Kuwait pertaining to hospital admissions with AMI between 1997 and 2006 in an effort to study the influence of the Islamic holiday season on AMI. For the purpose of this study, only admissions during the four days of the Eid-al-Fitr festival and 60 days prior to and following it in each of the six years, were included. A total of 964 admissions were counted. Zubaid et al. (2006) used Poisson probability to see if the observed admissions during the Eid holidays were significantly different from the days preceding and following it. In the 24 Eid days, there were 45 admissions, compared to the 31.24 admissions that should have been expected, indicating that the holidays were associated with a significant increase in admissions. As for the individual days, only the second day of Eid was found to be associated with a significantly higher number of admissions. These results were further confirmed by LOESS regression modeling. Zubaid et al. (2006) explained the possible reasons for this observation on the basis of consumption of heavy meals and smoking during the festival, directly following a period of fasting and abstinence from smoking. Zubaid et al. (2006) cautioned that the study was only a random observation from a hospital registry and could not offer evidence for a casual relationship.

Lebanon

[See: Qatar > Chaikhouni et al., 1993; Kuwait > Olusi et al., 1999].

Oman

[See: Qatar > Chaikhouni et al., 1993].

Palestine

[See: Kuwait > Al-Owaish et al., 1983; Olusi et al., 1999; Qatar > Chaikhouni et al., 1993;].

Qatar

Chaikhouni et al. (1993) retrospectively studied all patients diagnosed with an acute myocardial infarction betweem 1982 and 1990 in Qatar. The subject population consisted of 2,515 patients (86.6% males; mean age: 51-years), of which 853 were Qatari nationals. Another 422 were Arabs belonging to Egypt (136), Jordan/Palestine (130), Lebanon, Yemen, Oman, Sudan, Somalia, Syria, and other Arabian Gulf States. The patients were divided into two groups; one comprising of patients lower than age 40-years, and the other above. The overall mortality was 10%. However, it was noticed that patients in the age group of 40-years or younger had a lower mortality when compared to those in the older age group. The younger age-group consisted predominantly of Asian males. Qatari patients, on the other hand were more in the older age group, and therefore, had a high mortality (16%). Age, male gender, and smoking were found to be significant risk factors for MI in this population. However, mortality was significantly associated with older age, female gender, and anteroseptal infarction.

Hajar (2000) studied the ten-year mortality due to Acute Myocardial Infarction in Qatar from 1979-1999. The results showed a four-fold increase in the number of hospital admissions due to AMI from 1979 to 1999 (about 110 cases to more than 375 cases). However, mortality decreased significantly from 16.6% to 9.9% in the same years. Hajar (2000) attributed this decrease in mortality to the introduction and use of thrombolytic therapy. In fact, 55% of the patients admitted due to AMI in the year 1999 received thrombolytic therapy. The mortality was found to be significantly lower (4.4%) in this group, as compared to the group that did not receive this therapy (16.5%). [Hajar R. Ten-yearly mortality due to acute myocardial infarction in Qatar from 1979 to 1999. Heart Views. 2000; 1(6):237.]

Later, Hajar (2001) studied the impact of diabetes mellitus on mortality due to AMI in Qatar based on a 10-year data from 1990 to 2000. Of the total of 4666 patients (239 Qataris) admitted in this period, there were 870 deaths. A total of 1557 patients were diabetic (30%), and the mortality rate in this group was at 14.5% (227 deaths). Among the exclusively Qatari patient group too, mortality was slightly higher among diabetics (133 deaths out of 733 patients; 18%), as compared to the non-diabetic patients (106 deaths out of 657 patients; 16%). Interestingly, Qatari females were found to have a higher mortality rate (23.3%) when compared to Qatari males (15.2%).

A cohort study was carried out by Bener et al. (2005) on patients hospitalized in Qatar between the years 1999 and 2003 to find the association between stroke and Acute Myocardial Infarction. During this period, 166 Qatari patients were hospitalized with stroke. Of these, 91 (38.9%) had AMI, the incidence of which was higher in males than in females. The prevalence of AMI was higher in subjects <50-years of age. Mortality was found to be significantly higher among the stroke patients with AMI. A stepwise logistic regression analysis showed that smoking and hypercholesterolemia were strong predictors for AMI in patients with stroke. Bener et al. (2005) concluded that a strong association exists between stroke, AMI, and related risk factors.

Saudi Arabia

Wakil et al. (2016) carried out a genome wide association study to identify gene loci associated with Coronary Artery Disease (CAD) or Myocardial Infarction (MI) in the Saudi Arabian population.  The study included 2668 CAD/MI affected patients and 3000 healthy controls that were recruited for the study based on their coronary angiography and echocardiography results.  All recruits were of Saudi Arabian origin.  Genotyping and statistical analysis revealed several gene loci associated with MI.  The SNPs rs10757274_G and rs1333045_C belonging to the CDKN2A/B gene and the SNP rs9982601_T belonging to the KCNE2 gene showed the most statistically significant association with MI (p=2.98E-08, p=1.15E-08 and p=3.49E-08 respectively).  This was in accordance with previously reported studies in other ethnic groups. However, the authors noted that some of the variants discovered in the genes differed from previous reports, suggesting ethnicity-related variation.  The RNF13 gene contained the SNP rs414111047_A that showed a conspicuous association with MI (p=1.07E-07).  The SNPs rs32793_G (PDZD2 gene), rs16880442_G (ITGA1 gene), rs4739066_A (YTHDF3 gene) and rs7211079_A (EIF4A3 gene) were all found to be weakly associated with MI (p=6.13E-06, p=8.56E-06, p=2.47E-06 and p=4.81E-06 respectively).  Additionally, the study estimated the heritability of MI in Saudi Arabs to be approximately 44%.    

Abdulazeez et al. (2016) performed a case-control study in order to investigate the association of 12 risk variants located at 9p21.3 with myocardial infarction (MI) in the Saudi Arabian population.  The study included 250 Saudi patients with CAD who had experienced an MI and 252 age matched healthy controls with no history of CAD.  Results showed a significant difference in the genotypic distribution of four SNPs (rs564398, rs4977574, rs2891168, and rs1333042) in the CDKN2BAS gene between cases and controls.  The study identified three protective haplotypes (TAAG, AGTA and GGGCC) and a risk haplotype (TGGA) for the development of CAD.  This study was in line with previous studies conducted worldwide indicating that the SNPs located in the intronic region of the CDKN2B-AS1 gene were associated with CAD.

Vatte et al. (2016) performed a case-control study on 1002 angiographically defined CAD patients from the Eastern Province of Saudi Arabia and 984 CAD-free controls based on echocardiogram and negative family history.  The aim was to understand whether the KIF6 719Arg allele was associated with CAD and non-fatal MI in the studied group of patients.  Of the patients, 778 had experienced at least one MI, 24 had experienced between three to six MIs and 200 had no history of MI.  Genotyping revealed a lack of association between KIF6 Trp719Arg SNP and CAD or MI.  The authors concluded that carriers of the KIF6 719Arg allele did not have an increased risk of CAD and non-fatal MI among patients from Eastern Province of Saudi Arabia.  This finding was in line with other previous studies conducted worldwide. 

Somalia

[See: Qatar > Chaikhouni et al., 1993]

Sudan

[See: Qatar > Chaikhouni et al., 1993].

Syria

[See: Qatar > Chaikhouni et al., 1993]

Yemen

[See: Qatar > Chaikhouni et al., 1993].

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