Association of the BB genotype of the ABO gene with the risk of acute myocardial infarction in hospital-based study.

Objectives: The ABO gene locus has been identified to be associated with myocardial infarction in patients with coronary heart disease. The primary focus of this hospital-based study was to explore the relationship of ABO blood groups and ABO genotypes with acute myocardial infarction (AMI) in Karachi, Pakistan. Methods: In a comparative cross-sectional study, an equal number of adult AMI patients and healthy controls (n=275 in each group; age range 30-70 years, both males and females) were recruited from the Aga Khan University and NICVD, Karachi, with informed consent. The blood samples were analyzed for ABO blood groups and other biomarkers. PCR followed by RFLP techniques were employed for determining the ABO genotypes. Multinomial regression was used to evaluate the association of genotypes with the risk of AMI. Results: Thirteen different combinations of ABO genotypes were observed while the O2O2 and A2A2 genotypes were not detected. No significant association based on the distribution of blood groups A, B, O and AB among AMI patients and healthy individuals was observed. The odds of AMI were 3.32 times in subjects with BB genotype as compared to subjects with OO genotypes after adjustment of age, gender, body mass index, heart rate, total cholesterol, and waist circumference [AOR (95% CI) =3.32 (1.36-8.08), p-value =0.008]. Conclusion: Our hospital-based study indicates that ABO genotype BB was significantly associated with the risk of AMI. This harmful effect of the BB genotype could have a possible relationship with AMI's development in the Pakistani population.

Ten years risk assessment of atherosclerotic cardiovascular disease using Astro-CHARM and pooled cohort equation in a south Asian sub-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 the 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 sub-population. METHODS: A total of 386 residents of all six districts of Karachi with no ASCVD were enrolled in the study through an exponential non-discriminative referral snowball sampling technique. 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 labeled 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 and specific risk estimators for this South Asian sub-population. Our study provides the first step towards developing a risk assessment guided decision-making protocol for primary prevention of ASCVD in this population.

Association of vitamin D deficiency and VDBP gene polymorphism with the risk of AMI in a Pakistani population.

OBJECTIVE: To investigate the relationship of vitamin D deficiency and risk of AMI in a Pakistani population, and to find out any association between vitamin D binding protein (VDBP) genotypes and risk of AMI in this population. METHODS: In a comparative cross-sectional study, 246 patients (age: 20-70 years; 171 males and 75 females) with first AMI were enrolled with informed consent. Similarly, 345 healthy adults (230 males and 115 females) were enrolled as controls. Their fasting serum samples were analyzed for 25 (OH) vitamin D, lipids and other biomarkers using kit methods, while DNA was analyzed for VDBP genotypes using PCR-RFLP based methods. Chi-squared test and logistic regression were used for association of vitamin D deficiency and VDBP genotypes with AMI. RESULTS: Mean serum concentration of 25(OH) vitamin D was significantly lower in AMI patients compared to healthy subjects (p=0.015) and percent vitamin D deficiency was higher in AMI patients compared to healthy subjects (p=0.003). VDBP IF-IF genotype was positively associated with the risk of AMI in subject above 45 years after adjusting for potential confounders [OR = 9.86; 95% CI=1.16 to 83.43]. CONCLUSION: Vitamin D deficiency and VDBP IF-IF genotype are associated with AMI in Pakistani adults.

Polymorphisms in MTHFR, MS and CBS genes and premature acute myocardial infarction in a Pakistani population.

High prevalence of premature coronary heart disease in Pakistanis compared to other populations points towards the genetic predisposition of this population to develop this disease. Since no investigations have been carried out in Pakistan to study the relationship of polymorphisms in genes involved in homocysteine cycle, the objective of the present study was to find out if there is any association of methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C; methionine synthase (MS) A2756G; cystathionine-ß-synthase (CBS) 844ins68, G919A polymorphisms with premature acute myocardial infarction (AMI) in a population of Pakistani patients with this disease. In a cross-sectional study, DNA samples of 143 AMI patients (age <45 years) and 153 healthy controls were genotyped for the above mentioned polymorphisms using PCR-RFLP methods. Plasma/serum samples of both patients and healthy controls were screened for homocysteine, folate and vitamin B12. One way ANOVA and chi-squared test were used for analysis of data. Mean plasma homocysteine levels in premature AMI patients and healthy controls were found to be 23±17.2 and 23±13.4 µmol/l, respectively which are higher than the upper normal limit of this biomarker (15µmol/l). MTHFR 677 CT genotype in healthy controls and MTHFR 677 TT genotype in AMI patients were found to have significantly increased levels of plasma homocysteine (p value <0.05), while all other polymorphisms did not show any significant difference in mean levels of homocysteine between AMI patients and healthy controls. Moreover, no association was observed between MTHFR C677T, A1298C; MS A2756C; CBS844ins68 polymorphisms and premature AMI in this population. This indicates that common polymorphisms in MTHFR, MS and CBS genes have no role in premature AMI in Pakistani population.

Major dietary patterns and risk of acute myocardial infarction in young, urban Pakistani population.

OBJECTIVE: To investigate the role of dietary intake in the development of premature acute myocardial infarction (AMI) in a hospital-based Pakistani population in Karachi. METHODS: In a case control study, 203 consecutive patients (146 males and 57 females) with their first AMI and age below 45 years were enrolled with informed consent. Similarly, 205 gender and age matched (within 3 years) healthy adults were also included as controls. Dietary intake of both cases and controls was assessed by using a simple 14-item food frequency questionnaire. Using factor analysis, 3 major dietary patterns- prudent dietary pattern, combination dietary pattern and western dietary pattern were identified. Fasting plasma/serum of both cases and controls were analyzed for homocysteine, folate, vitamin B12, blood Pb, ferritin, cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides. ANOVA and conditional logistic regression were used to predict the association of dietary patterns with AMI. RESULTS: Consumption of prudent diet, characterized by high consumption of legumes, vegetables, wheat, chicken and fruits, is protective against the risk of premature AMI. Moderate to high consumption of combination diet, characterized by high intake of eggs, fish, fruits, juices and coffee was associated with decreased risk of AMI. No association was observed between western diet, characterized by high intake of meat, fish and tea with milk and risk of AMI. CONCLUSIONS: Consumption of a prudent dietary pattern and a combination dietary pattern is protective against the risk of AMI in a Pakistani population.

Association of alkaline phosphatase with acute myocardial infarction in a population with high prevalence of hypovitaminosis D.

BACKGROUND: Since Pakistanis have high prevalence of hypovitaminosis-D as well as acute myocardial infarction (AMI), the objective of the study was to investigate the relationship between vitamin-D deficiency and risk of AMI in a hospital-based population and to identify major risk factors for this disease. METHODS: Fasting serum samples from 66 consecutive AMI patients [age 30-70 y] and 132 gender and age-matched (within 5 y) healthy controls were analyzed for concentrations of glucose, total-cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, calcium, inorganic phosphate, alkaline phosphatase (ALP), bone-ALP, parathyroid hormone (PTH), 25(OH) vitamin-D (25(OH)D) and alanine aminotransferase. RESULTS: Mean concentrations of serum 25(OH)D, PTH, total-ALP, bone-ALP, LDL-cholesterol, HDL-cholesterol and glucose were significantly different compared to healthy controls (p<0.05). Percent vitamin-D deficiency/insufficiency (levels<30 ng/ml) was significantly greater in AMI patients compared to controls (93.9% vs.75.8%; p=0.001). Multiple conditional logistic regression analysis revealed that increased levels of 25(OH)D were associated with decreased risk of AMI [MAOR (95% CI)=0.821 (0.718, 0.940); p=0.004]. Hypertension and smoking were positively associated with AMI. CONCLUSIONS: Increased vitamin-D levels were associated with decreased risk of AMI, while serum glucose, bone-ALP, hypertension and smoking were positively associated with it. Association of bone-ALP with AMI in hypovitaminosis-D is a novel finding of this study.

Association of body iron status with the risk of premature acute myocardial infarction in a Pakistani population.

BACKGROUND: Coronary artery disease is very common in Pakistani population. Some of the studies carried out on Western populations have shown a relationship between body iron status as determined by the ratio of concentrations of serum soluble transferrin receptor (sTfR) to ferritin and the risk of acute myocardial infarction (AMI). In order to investigate whether increased body iron status has any relationship with the risk of premature AMI in Pakistani population, a case-control study was carried out. METHODOLOGY/PRINCIPAL FINDINGS: In this case-control study, 203 consecutive AMI patients [146 males and 57 females; age range 18-45 years] admitted to the National Institute for Cardiovascular Diseases, Karachi, were enrolled with informed consent. In addition, 205 healthy controls whose gender and age (within 3 years) matched the patients, and who had a similar socio-economic background were recruited. Fasting venous blood was obtained and assessed for plasma/serum folate, vitamin B12, homocysteine, total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, sTfR and ferritin and blood lead. It was found that serum concentration of ferritin and blood lead levels were significantly higher in AMI patients compared to their age and gender-matched healthy controls (p value <0.05), while the concentrations of vitamin B12 and HDL-cholesterol were significantly lower in AMI patients compared to controls (p value <0.01). The ratio of sTfR to ferritin was significantly lower in AMI patients compared to controls [mean ± SD/median (IQR) values 84.7 ± 295/28.9 (38.4) vs 255 ± 836/49.4 (83.8), respectively; p value <0.001]. Compared with the highest quartile of sTfR/ferritin (low body iron status), the OR for the risk of AMI was 3.29(95% CI, 1.54-7.03) for the lowest quartile (quartile 1) when the model was adjusted for vitamin B12 and HDL-cholesterol (p value for trend <0.01). CONCLUSIONS/SIGNIFICANCE: This study shows a positive association between total body iron status and risk of premature AMI in a Pakistani population.