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Background: Severe coronary artery disease (CAD) represents an advanced arterial narrowing, often associated with critical complications like myocardial infarction and angina. This study aimed to comprehensively investigate determinants of severe and multi-vessel CAD manifestations., Methods: One thousand nine hundred patients with severe and multivessel CAD (stenosis > 70%) were recruited along with 1,056 controls without stenosis. Associations using a genotyping panel comprising 159 Single Nucleotide Polymorphisms (SNPs) previously implicated in CAD pathogenesis were examined and these associations were replicated using the UK Biobank cohort (N = 29,970)., Results: The investigation identified 14 genetic associations with severe CAD, of which 7 were also associated with multivessel disease. Notably, PHACTR1 SNP (rs9349379*G) showed a higher association with severe and multivessel CAD in individuals aged ≤ 65, indicating a higher risk of early disease onset. Conversely, the APOC1/APOE SNP (rs445925*T) is associated with reduced susceptibility to severe CAD and multivessel disease in individuals aged over 65, indicating a persistent negative association., Conclusions: Following replication of the associations in the large UK Biobank dataset, it was found that patients carrying the rs9349379*G variant in the PHACTR1 gene are at risk of developing severe or multivessel disease. Conversely, the rs445925*T variant in APOC1/APOE is associated with reduced susceptibility to severe CAD and multivessel disease, highlighting the significance of this genetic variant in these specific CAD presentations. This study contributes to a better understanding of CAD heterogeneity, paving the way for tailored management strategies based on genetic profiles., (© 2024. The Author(s).)

Background: Type 2 Diabetes (T2D) is influenced by genetic, environmental, and ageing factors. Ageing pathways exacerbate metabolic diseases. This study aimed to examine both clinical and genetic factors of T2D in older adults., Methods: A total of 2,909 genotyped patients were enrolled in this study. Genome Wide Association Study was conducted, comparing T2D patients to non-diabetic older adults aged ≥ 60, ≥ 65, or ≥ 70 years, respectively. Binomial logistic regressions were applied to examine the association between T2D and various risk factors. Stepwise logistic regression was conducted to explore the impact of low HDL (HDL < 40 mg/dl) on the relationship between the genetic variants and T2D. A further validation step using data from the UK Biobank with 53,779 subjects was performed., Results: The association of T2D with both low HDL and family history of T2D increased with the age of control groups. T2D susceptibility variants (rs7756992, rs4712523 and rs10946403) were associated with T2D, more significantly with increased age of the control group. These variants had stronger effects on T2D risk when combined with low HDL cholesterol levels, especially in older control groups., Conclusions: The findings highlight a critical role of age, genetic predisposition, and HDL levels in T2D risk. The findings suggest that individuals over 70 years who have high HDL levels without the T2D susceptibility alleles may be at the lowest risk of developing T2D. These insights can inform tailored preventive strategies for older adults, enhancing personalized T2D risk assessments and interventions., (© 2024. The Author(s).)

Aims: Type 2 diabetes (T2D) and coronary artery disease (CAD) often coexist and share genetic factors.This study aimed to investigate the common genetic factors underlying T2D and CAD in patients with CAD., Methods: A three-step association approach was conducted: a) a discovery step involving 943 CAD patients with T2D and 1,149 CAD patients without T2D; b) an eliminating step to exclude CAD or T2D specific variants; and c) a replication step using the UK Biobank data., Results: Ten genetic loci were associated with T2D in CAD patients. Three variants were specific to either CAD or T2D. Five variants lost significance after adjusting for covariates, while two SNPs remained associated with T2D in CAD patients (rs7904519*G: TCF7L2 and rs17608766*C: GOSR2). The T2D susceptibility rs7904519*G was associated with increased T2D risk, while the CAD susceptibility rs17608766*C was negatively associated with T2D in CAD patients. These associations were replicated in a UK Biobank data, confirming the results., Conclusions: No significant common T2D and CAD susceptibility genetic association was demonstrated indicating distinct disease pathways. However, CAD patients carrying the T2D susceptibility gene TCF7L2 remain at higher risk for developing T2D emphasizing the need for frequent monitoring in this subgroup., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background and Objectives: High homocysteine levels are associated with increased risk of hypertension and stroke. Homocysteine is metabolized by the methylenetetrahydrofolate reductase ( MTHFR ). We aimed to investigate the levels of homocysteine and their association with hypertension, stroke, and antihypertensive medication usage in patients with different MTHFR C677T genotypes., Methods and Results: Genotype frequency of MTHFR polymorphism was performed, and plasma homocysteine levels were measured in 2,640 adult Lebanese patients. Hypertension, history of stroke, and list of medications were documented, among other clinical and demographic parameters. The TT mutant genotype and the T mutant allele of MTHFR were more prevalent in hyperhomocysteinemia (HHcy) and H-hypertensive (H-HTN, defined as hypertension with hyperhomocysteinemia) patients when compared to non-HHcy subjects and non H-HTN patients respectively. Homocysteine levels were significantly higher in hypertensive patients specifically among those on diuretics. A higher level of homocysteine was found in hypertensive patients with the MTHFR T allele compared to patients carrying the C allele. Among the T allele carriers, the average plasma homocysteine level was 13.3 ± 0.193 μmol/L for hypertensive subjects compared to 11.9 ± 0.173 μmol/L (non-hypertensives). Furthermore, homocysteine levels significantly correlated with stroke risk in patients with the T alleles., Conclusions: We found an association of homocysteine with hypertension, hypertensive medication, and stroke risk among patients with the MTHFR T allele and the TT genotype. The association of diuretics therapy with higher homocysteine levels calls for routine measurements and therapeutic control of homocysteine in patients on diuretic, to improve health-related outcomes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background and Objective: Coronary artery disease (CAD) is a major cause of death worldwide. Revascularization via stent placement or coronary artery bypass grafting (CABG) are standard treatments for CAD. Despite a high success rate, these approaches are associated with long-term failure due to restenosis. Risk factors associated with restenosis were investigated using a case-control association study design., Methods: Five thousand two hundred and forty-two patients were enrolled in this study and were assigned as follows: Stenosis Group: 3570 patients with CAD >50% without a prior stent or CABG (1394 genotyped), and Restenosis Group: 1672 patients with CAD >50% and prior stent deployment or CABG (705 genotyped). Binomial regression models were applied to investigate the association of restenosis with diabetes, hypertension, and dyslipidemia. The genetic association with restenosis was conducted using PLINK 1.9., Results: Dyslipidemia is a major risk factor (Odds Ratio (OR) = 2.14, P-value <0.0001) for restenosis particularly among men (OR = 2.32, P < 0.0001), while type 2 diabetes (T2D) was associated with an increased risk of restenosis in women (OR = 1.36, P = 0.01). The rs9349379 ( PHACTR1) and rs264 ( LPL ) were associated with an increased risk of restenosis in our patients. PHACTR1 variant was associated with increased risk of restenosis mainly in women and in diabetic patients, while the LPL variant was associated with increased risk of restenosis in men., Conclusion: The rs9349379 in PHACTR1 gene is significantly associated with restenosis, this association is more pronounced in women and in diabetic patients. The rs264 in LPL gene was associated with increased risk of restenosis in male patients., Competing Interests: The authors declare no conflicts of interest in this work., (© 2023 Al Hageh et al.)

Backgrounds and Aims: The role of Lipoprotein(a) (Lp(a)) in increasing the risk of cardiovascular diseases is reported in several populations. The aim of this study is to investigate the correlation of high Lp(a) levels with the degree of coronary artery stenosis., Methods: Two hundred and sixty-eight patients were enrolled for this study. Patients who underwent coronary artery angiography and who had Lp(a) measurements available were included in this study. Binomial logistic regressions were applied to investigate the association between Lp(a) and stenosis in the four major coronary arteries. The effect of LDL and HDL Cholesterol on modulating the association of Lp(a) with coronary artery disease (CAD) was also evaluated. Multinomial regression analysis was applied to assess the association of Lp(a) with the different degrees of stenosis in the four major coronary arteries., Results: Our analyses showed that Lp(a) is a risk factor for CAD and this risk is significantly apparent in patients with HDL-cholesterol ≥35 mg/dL and in non-obese patients. A large proportion of the study patients with elevated Lp(a) levels had CAD even when exhibiting high HDL serum levels. Increased HDL with low Lp(a) serum levels were the least correlated with stenosis. A significantly higher levels of Lp(a) were found in patients with >50% stenosis in at least two major coronary vessels arguing for pronounced and multiple stenotic lesions. Finally, the derived variant (rs1084651) of the LPA gene was significantly associated with CAD., Conclusion: Our study highlights the importance of Lp(a) levels as an independent biological marker of severe and multiple coronary artery stenosis., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Al Hageh et al.)

In Lebanon, previous studies have indicated an onset of cardiovascular diseases 12 years earlier than in other parts of the world, suggesting the presence of additional risk factors specific to Lebanon. Measurements of airborne particles in Lebanon surpass the recommendations of the World Health Organization by over 150%. This study examined the association between obstructive coronary artery disease (CAD), assessed by a novel marker calculated from coronary catheterization, and markers of air pollution, specifically polycyclic aromatic hydrocarbons (PAHs), in a cohort of 258 patients seen at the American University of Beirut Medical Center since 2014. The concentrations of four types of hydroxylated polycyclic aromatic hydrocarbons (OHPAHs), 2-OHNAP, 2-OHFLU, 3-OHPHE, and 1-OHPYR, were measured in the urine samples of these patients using high performance liquid chromatography coupled with fluorescence detector. Results showed that the OHPAH concentrations were higher than what was reported in high-income countries and, most notably, the levels for non-smokers in this study were higher than those of smokers and some occupational workers in other countries. This implies that patients were exposed to high levels of PAHs, which originate from combustion sources. In particular, 1-OHPYR showed a significant association with presence of obstructive CAD, even after adjusting for covariates like age, sex, and diabetes. Smokers or not, this association has implications for public health and calls for urgent need to pass regulations to reduce the emissions of PAH sources, such as cars, diesel generators, and incinerators., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Cardiac troponin I ( TNNI3 ) gene mutations account for 3% of hypertrophic cardiomyopathy and carriers have a heterogeneous phenotype, with increased risk of sudden cardiac death (SCD). Only one mutation (p.Arg21Cys) has been reported in the N terminus of the protein. In model organisms, it impairs PKA (protein kinase A) phosphorylation, increases calcium sensitivity, and causes diastolic dysfunction. The phenotype of this unique mutation in patients with hypertrophic cardiomyopathy remains unknown., Methods: We sequenced 29 families with hypertrophic cardiomyopathy enriched for pediatric-onset disease and identified 5 families with the TNNI3 p.Arg21Cys mutation. Using cascade screening, we studied the clinical phenotype of 57 individuals from the 5 families with TNNI3 p.Arg21Cys-related cardiomyopathy. We performed survival analysis investigating the age at first SCD in carriers of the mutation., Results: All 5 families with TNNI3 p.Arg21Cys were from South Lebanon. TNNI3 p.Arg21Cys-related cardiomyopathy manifested a malignant phenotype-SCD occurred in 30 (53%) of 57 affected individuals at a median age of 22.5 years. In select carriers without left ventricular hypertrophy on echocardiogram, SCD occurred, myocyte disarray was found on autopsy heart, and tissue Doppler and cardiac magnetic resonance imaging identified subclinical disease features such as diastolic dysfunction and late gadolinium enhancement., Conclusions: The TNNI3 p.Arg21Cys mutation has a founder effect in South Lebanon and causes malignant hypertrophic cardiomyopathy with early SCD even in the absence of hypertrophy. Genetic diagnosis with this mutation may be sufficient for risk stratification for SCD.

Coronary anomalies occur in about 1% of the general population and in severe cases can lead to sudden cardiac death. Coronary computed tomography angiography and magnetic resonance imaging have been deemed appropriate for the evaluation of coronary anomalies by accurately allowing the noninvasive depiction of coronary artery anomalies of origin, course, and termination. The aim of this article is to describe and illustrate a comprehensive array for the classification of coronary artery anomalies.

Low serum levels of high-density lipoprotein cholesterol (HDL-C) have been shown to be a risk factor for coronary artery disease independent of low-density lipoprotein cholesterol (LDL-C) in different populations. In this study, we investigated genetic variants through genome-wide association studies to determine their association with HDL-C levels in a sample of 2,700 patients. We identified several SNPs associated with HDL-C levels in the Lebanese population using unadjusted and adjusted by biological factors models. We replicated the association of rs3764261 within CETP with HDL-C levels in the study population, and found other previously unidentified SNPs to be significant at the suggestive level, in both previously identified and unidentified genes. This paper reports the first genome-wide analysis of HDL-C in the Lebanese, Middle Eastern, population and supports the importance of genome-wide association studies across different and minor ethnicities to understand better the etiology of complex human diseases., Competing Interests: The authors have declared that no competing interests exist.

Background: Cardiomyopathies affect more than 0.5% of the general population. They are associated with high risk of sudden cardiac death, which can result from either heart failure or electrical abnormalities. Although different mechanisms underlie the various types of cardiomyopathies, a principal pathology is common to all and is usually at the level of the cardiac muscle. With a relatively high incidence rate in most countries, and a subsequent major health burden on both the families and governments, cardiomyopathies are gaining more attention by researchers and pharmaceutical companies as well as health government bodies. In Lebanon, there is no official data about the spectrum of the diseases in terms of their respective prevalence, clinical, or genetic profiles., Methods: We used exome sequencing to unravel the genetic basis of idiopathic cases of cardiomyopathies in Lebanon, a relatively small country with high rates of consanguineous marriages., Results: Five cases were diagnosed with different forms of cardiomyopathies, and exome sequencing revealed the presence of already documented or novel mutations in known genes in three cases: LMNA for an Emery Dreifuss Muscular Dystrophy case, PKP2 for an arrhythmogenic right ventricle dysplasia case, and MYPN for a dilated cardiomyopathy case. Interestingly two brothers with hypertrophic cardiomyopathy have a novel missense variation in NPR1, the gene encoding the natriuretic peptides receptor type I, not reported previously to be causing cardiomyopathies., Conclusion: Our results unravel novel mutations in known genes implicated in cardiomyopathies in Lebanon. Changes in clinical management however, require genetic profiling of a larger cohort of patients.

Background: Coronary artery disease (CAD) accounts for more than half of all cardiovascular events. Stress testing remains the cornerstone for non-invasive assessment of patients with possible or known CAD. Clinical utilization reviews show that most patients presenting for evaluation of stable CAD by stress testing are categorized as low risk prior to the test. Attempts to enhance risk stratification of individuals who are sent for stress testing seem to be more in need today. The present study compares artificial neural networks (ANN)-based prediction models to the other risk models being used in practice (the Diamond-Forrester and the Morise models)., Methods: In our study, we prospectively recruited patients who were 19 years of age or older, and were being evaluated for coronary artery disease with imaging-based stress tests. For ANN, the network architecture employed a systematic method, where the number of neurons is changed incrementally, and bootstrapping was performed to evaluate the accuracy of the models., Results: We prospectively enrolled 486 patients. The mean age of patients undergoing stress test was 55.2 ± 11.2 years, 35% were women, and 12% had a positive stress test for ischemic heart disease. When compared to Diamond-Forrester and Morise risk models, the ANN model for predicting ischemia provided higher discriminatory power (DP)(1.61), had a negative predictive value of 98%, Sensitivity 91% [81%-97%], Specificity 65% [60%-79%], positive predictive value 26%, and a potential 59% reduction of non-invasive imaging., Conclusion: The ANN models improved risk stratification when compared to the other risk scores (Diamond-Forrester and Morise) with a 98% negative predictive value and a significant potential reduction in non-invasive imaging tests.

Background: Waterpipe smoking is a rising global public health epidemic perceived by many users to be less harmful, though its toxicity overlaps or even exceeds that of cigarette smoking. Short-term cardiovascular changes due to waterpipe smoking are well established, but longer-term health impacts are still not fully elucidated., Objective: We aim to investigate the association of waterpipe smoking with myocardial infarction among patients undergoing cardiac catheterization., Methods: The study was performed on Lebanese patients referred for cardiac catheterization. Patient's blood was collected for metabolic measures and questionnaires were filled out to include socio-demographic, behavioral and pertinent medical characteristics of the study subjects., Results: Myocardial infarction is significantly and independently associated with waterpipe smoking, with odds ratio (OR) of 1.329 (95% CI: [1.04-1.68]; p = .021), which is lower than that for cigarette smoking (OR = 1.87, 95% CI: [1.63-2.15]; p < .001). Only diabetes showed significant association with waterpipe smoking among MI enrollees (OR = 1.66, 95%CI: [1.04-2.63]; p = .032)., Conclusion: The study provides yet another evidence for the adverse cardiovascular effects of waterpipe smoking on a clinical level. The harmful effects of waterpipe smoking should be underscored by health care professionals.

Background: Elevated homocysteine (Hc) levels have a well-established and clear causal relationship to epithelial damage leading to coronary artery disease. Furthermore, it is strongly associated with other metabolic syndrome variables, such as hypertension, which is correlated with type II diabetes mellitus (T2DM). Studies on T2DM in relation to Hc levels have shown both positive and negative associations. The aim of the present study is to examine the relationship between Hc levels and risk of T2DM in the Lebanese population., Methods: We sought to identify whether Hc associates positively or negatively with diabetes in a case-control study, where 2755 subjects enrolled from patients who had been catheterized for coronary artery diagnosis and treatment. We further sought to identify whether the gene variant MTHFR 667C>T is associated with T2DM, and how Hc and MTHFR 667C>T also impact other correlates of T2DM, including the widely used diuretics in this study population., Results: We found that Hc levels were significantly reduced among subjects with diabetes compared to those without diabetes when adjusted for all potential confounders (OR 0.640; 95% CI [0.44-0.92]; p  = 0.0200). The associations between Hc levels and other variates contradicted the result: hypertension associates positively with high Hc levels, and with T2DM. The MTHFR 667C>T only associated significantly with high Hc levels., Conclusion: These results suggest population-specific variations among a range of mechanisms that modulate the association of Hc and T2DM, providing a probe for future studies.

Background: Sedentary lifestyle has become prevalent in our community. Recent data showed controversy on the effect of regular exercise on left ventricular compliance and myocardial relaxation., Hypothesis: We sought to assess whether physical inactivity is an independent predictor of diastolic dysfunction in or community, after adjustment for several covariates., Methods: Consecutive outpatients presenting to the echocardiography laboratory between July 2013 and June 2014 were prospectively enrolled. Clinical variables were collected prospectively at enrollment. Patients were considered physically active if they exercised regularly ≥3× a week, ≥30 minutes each time. The primary endpoint was presence of diastolic dysfunction., Results: The final cohort included 1356 patients (mean age [SD] 52.9 [17.4] years, 51.3% female). Compared with physically active patients, the 1009 (74.4%) physically inactive patients were older, more often female, and had more comorbidities and worse diastolic function (51.3% vs 38.3%; P < 0.001). On univariate analysis, physical inactivity was associated with 70% increased odds of having diastolic dysfunction (odds ratio: 1.70, 95% confidence interval: 1.32-2.18, P < 0.001). There was significant interaction between physical activity and left ventricular mass index (LVMI; P = 0.026). On multivariate analysis, patients who were physically inactive and had LVMI ≥ median had significantly higher odds of having diastolic dysfunction (odds ratio: 2.82, 95% confidence interval: 1.58-5.05, P < 0.001)., Conclusions: In a large, prospectively enrolled cohort from a single tertiary center in the Middle East, physically inactive patients with increased LVMI had 2- to 3-fold increased odds of having diastolic dysfunction after multivariate adjustment., (© 2016 Wiley Periodicals, Inc.)

Cultural, dietary, and lifestyle factors are the main modulators of type 2 diabetes mellitus (T2DM) disease risk. Coffee is one of the most popular worldwide beverages, and recent epidemiological studies have showed that coffee consumption is associated with a lower risk of T2DM. This study investigates the impact of coffee intake on T2DM risk and assesses the effect of CYP variants with caffeine exposures on T2DM. Data from 7,607 study subjects were analyzed by logistic regression models, among whom 3,290 GWAS data were available for CYP variants association studies using Plink analysis. These data suggest a protective relationship for women, but not for men; however, the results were not statistically significant in this dataset and there is a significant interaction in favor of women regarding heavy coffee consumption. The interaction between male gender and heavy coffee consumption becomes significant, thereby tending to cancel the protective effect of coffee for males. CYP rs2470890 allele 'C' increases the odds of T2DM by a factor of around 1.2 but decreases the odds of caffeine boosting T2DM of 1.7 by a factor of 0.77. rs2470890 showed an association with T2DM only when the interaction with coffee was considered, thereby setting an example of genetic activation by dietary changes associating with metabolic syndrome., (© 2015 S. Karger AG, Basel.)

Background: The use of the Coronary Artery Calcium Score (CACS) for risk categorization instead of the Framingham Risk Score (FRS) or European Heart SCORE (EHS) to improve classification of individuals is well documented. However, the impact of reclassifying individuals using CACS on initiating lipid lowering therapy is not well understood. We aimed to determine the percentage of individuals not requiring lipid lowering therapy as per the FRS and EHS models but are found to require it using CACS and vice versa; and to determine the level of agreement between CACS, FRS and EHS based models., Methods: Data was collected for 500 consecutive patients who had already undergone CACS. However, only 242 patients met the inclusion criteria and were included in the analysis. Risk stratification comparisons were conducted according to CACS, FRS, and EHS, and the agreement (Kappa) between them was calculated., Results: In accordance with the models, 79.7% to 81.5% of high-risk individuals were down-classified by CACS, while 6.8% to 7.6% of individuals at intermediate risk were up-classified to high risk by CACS, with slight to moderate agreement. Moreover, CACS recommended treatment to 5.7% and 5.8% of subjects untreated according to European and Canadian guidelines, respectively; whereas 75.2% to 81.2% of those treated in line with the guidelines would not be treated based on CACS., Conclusion: In this simulation, using CACS for risk categorization warrants lipid lowering treatment for 5-6% and spares 70-80% from treatment in accordance with the guidelines. Current strong evidence from double randomized clinical trials is in support of guideline recommendations. Our results call for a prospective trial to explore the benefits/risks of a CACS-based approach before any recommendations can be made.

Background: More evidence is emerging on the strong association between chronic kidney disease (CKD) and cardiovascular disease. We assessed the relationship between coronary artery disease (CAD) and renal dysfunction level (RDL) in a group of Lebanese patients., Methods: A total of 1268 patients undergoing cardiac catheterization were sequentially enrolled in a multicenter cross sectional study. Angiograms were reviewed and CAD severity scores (CADSS) were determined. Estimated glomerular filtration rate (eGFR) was calculated and clinical and laboratory data were obtained. CKD was defined as eGFR < 60 ml/min. Logistic regression model was performed using multivariate analysis including all traditional risk factors associated with both diseases. ANOVA and the Tukeytestswere used to compare subgroups of patients and to assess the impact of each disease on the severity of the other., Results: Among the 82% patients who exhibited variable degrees of CAD, 20.6% had an eGFR < 60 ml/min. Logistic regression analysis revealed a bidirectional independent association between CAD and CKD with an OR = 2.01 (P < 0.01) and an OR = 1.99 (P < 0.01) for CAD and CKD frequencies, respectively. We observed a steady increase in the CADSS mean as eGFR declined and a progressive reduction in renal function with the worsening of CAD (P < 0.05). This correlation remained highly significant despite considerable inter-patient variability and was at its highest at the most advanced stages of both diseases., Conclusions: Our results show a strong, independent and graded bidirectional relationship between CAD severity and RDL. We propose to add CAD to the list of risk factors for the development and progression of CKD.

Isolated collapse of the left ventricle (LV) in diastole is not a very common finding on two-dimensional echocardiography. Reported cases in the literature were due to either loculated postoperative pericardial effusion/hematoma or left pleural effusion. To our knowledge, this is the first case report of LV diastolic collapse secondary to extra-thoracic compression., (© 2015, Wiley Periodicals, Inc.)

Background: The role of inflammation in coronary artery disease (CAD) pathogenesis is well recognized. Moreover, smoking inhalation increases the activity of inflammatory mediators through an increase in leukotriene synthesis essential in atherosclerosis pathogenesis., Aim: The aim of this study is to investigate the effect of "selected" genetic variants within the leukotriene (LT) pathway and other variants on the development of CAD., Methods: CAD was detected by cardiac catheterization. Logistic regression was performed to investigate the association of smoking and selected susceptibility variants in the LT pathway including ALOX5AP, LTA4H, LTC4S, PON1, and LTA as well as CYP1A1 on CAD risk while controlling for age, gender, BMI, family history, diabetes, hyperlipidemia, and hypertension., Results: rs4769874 (ALOX5AP), rs854560 (PON1), and rs4646903 (CYP1A1 MspI polymorphism) are significantly associated with an increased risk of CAD with respective odds ratios of 1.53703, 1.67710, and 1.35520; the genetic variant rs9579646 (ALOX5AP) is significantly associated with a decreased risk of CAD (OR 0.76163). Moreover, a significant smoking-gene interaction is determined with CYP1A1 MspI polymorphism rs4646903 and is associated with a decreased risk of CAD in current smokers (OR 0.52137)., Conclusion: This study provides further evidence that genetic variation of the LT pathway, PON1, and CYP1A1 can modulate the atherogenic processes and eventually increase the risk of CAD in our study population. Moreover, it also shows the effect of smoking-gene interaction on CAD risk, where the CYP1A1 MspI polymorphism revealed a decreased risk in current smokers.

A main underlying pathology of coronary artery disease is the deposition of cholesterol in the arteries supplying blood to the heart that leads to stenosis and myocardial infarction. We tested if dyslipidemia is a risk factor for coronary artery disease in the Lebanese population, and studied the role of the total cholesterol/HDL cholesterol (TC/HDL-C) ratio as a biological marker of coronary artery disease. We recruited 6,180 Lebanese patients undergoing cardiac catheterization. We conducted a cross-sectional association study between TC/HDL-C ratio and the number and type of vessels occluded in catheterized patients by controlling for confounding effects. The TC/HDL-C ratio ≥4 significantly predicts ≥50 % stenosis in all vessels individually with the odds ratio (OR) ranging from 1.22 to 1.92. The OR increased with increasing number of ≥50 % stenotic vessels (1.39 for 2 vessels and 1.64 for 3-4 vessels), as did risk due to diabetes, CAD family history, gender, and age. The younger than average age of onset subgroup shows a pronounced increase in risk for occlusion of the left main coronary artery due to TC/HDL-C ≥4 (OR 3.26). In conclusion, low levels of HDL-cholesterol and high levels TC/HDL-C ratio are strong biological markers of disease occurrence and severity in the Lebanese population.

Congenital vascular anomalies of the venous drainage in the chest affect both cardiac and non-cardiac structures. Collateral venous drainage from the left subclavian vein to the great cardiac vein is a rare venous drainage pattern. These anomalies present a diagnostic challenge. Multi-detector computed tomography (MDCT) is useful in the diagnosis and treatment planning of these clinically complex disorders. We present a case report of an 18-year-old Caucasian male who came to our institute for evaluation of venous drainage patterns to the heart. We describe the contrast technique of bilateral dual injection MDCT venography and the imaging features of the venous drainage patterns to the heart.

The onset of coronary artery disease (CAD) is influenced by cardiovascular risk factors that often occur in clusters and may build on one another. The objective of this study is to examine the relationship between hypertension and CAD age of onset in the Lebanese population. This retrospective analysis was performed on data extracted from Lebanese patients (n = 3,753). Logistic regression examined the association of hypertension with the age at CAD diagnosis after controlling for other traditional risk factors. The effect of antihypertensive drugs and lifestyle changes on the onset of CAD was also investigated. Results showed that hypertension is associated with late onset CAD (OR=0.656, 95% CI=0.504-0.853, p=0.001). Use of antihypertensive drugs showed a similar association with delayed CAD onset. When comparing age of onset in CAD patients with traditional risk factors such as hypertension, diabetes, hyperlipidemia, obesity, smoking and family history of CAD, the age of onset was significantly higher for patients with hypertension compared to those with any of the other risk factors studied (p < 0.001). In conclusion, hypertension and its treatment are associated with late coronary atherosclerotic manifestations in Lebanese population. This observation is currently under investigation to clarify its genetic and/or environmental mechanisms.

Background: The burden of diabetes in Lebanon requires well-targeted interventions for screening type 2 diabetes mellitus (T2DM) and prediabetes and prevention of risk factors. Newly recruited 998 Lebanese individuals, in addition to 7,292 already available, were studied to investigate the prevalence of diabetes, prediabetes and their associated risk factors., Methods: Participants had fasting blood sugar and glycohemoglobin tests in addition to a lipid profile. Clinical and demographic information were obtained from a detailed questionnaire. The relationship between T2DM, its risk factors, and its complications were tested. Comparisons of these risk factors among diabetics, healthy, and coronary artery disease (CAD) patients were performed., Results: The prevalence of T2DM significantly increased with increasing BMI (p < 0.0001). Exercise activity level negatively correlated with the disease (p = 0.002), whereas the prevalence of T2DM (p < 0.0001) and CAD family history (p = 0.006) positively correlated with the affection status. The mean levels of triglycerides and LDL-C were significantly higher in diabetics (1.87; 1.35) compared to individuals with prediabetes (1.63; 1.26) and unaffected controls (1.49; 1.19). People with T2DM showed a significant decrease in HDL-C levels. A strong correlation of overall hyperlipidemia with the diabetes affection status was shown (p < 0.0001). Other comorbid factors such as hypertension (p < 0.0001) and self-reported obesity (p < 0.0001) were highly associated with T2DM and prediabetes. Reproductive health of women showed a strong correlation between giving birth to a baby with a high weight and the occurrence of T2DM and prediabetes later in life (p < 0.0001). Retinopathy and peripheral neuropathy were significantly correlated with diabetes and prediabetes (p < 0.0001)., Conclusions: The present study shows an alarming prevalence of diabetes and prediabetes in the studied subgroups representative of the Lebanese population.

Background: Elevated levels of total plasma homocysteine are a risk factor for atherosclerotic disease., Aims: The rationale behind this study is to explore the correlation between degree and site of coronary lesion and hyperhomocysteinemia in Lebanese CAD patients and assess environmental and genetic factors for elevated levels of total plasma homocysteine., Methods: A total of 2644 patients were analyzed for traditional CAD risk factors. Logistic regression was performed to determine the association of hyperhomocysteinemia with degree and site of coronary lesions controlling for risk factors. Environmental and genetic factors for hyperhomocysteinemia were analyzed by logistic regression using a candidate gene approach., Results: Traditional risk factors were correlated with stenosis. Hyperhomocysteinemia associated with increased risk of overall stenosis, and risk of mild and severe occlusion in major arteries. Hyperhomocysteinemia and hypertension were highly correlated suggesting that hyperhomocysteinemia acts as a hypertensive agent leading to CAD. Diuretics and genetic polymorphisms in MTHFR and SLCO1B1 were associated with hyperhomocysteinemia., Conclusions: Hyperhomocysteinemia is a medical indicator of specific vessel stenosis in the Lebanese population. Hypertension is a major link between hyperhomocysteinemia and CAD occurrence. Genetic polymorphisms and diuretics' intake explain partly elevated homocysteine levels. This study has important implications in CAD risk prediction., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

The manifestation of coronary artery disease (CAD) follows a well-choreographed series of events that includes damage of arterial endothelial cells and deposition of lipids in the sub-endothelial layers. Genome-wide association studies (GWAS) of multiple populations with distinctive genetic and lifestyle backgrounds are a crucial step in understanding global CAD pathophysiology. In this study, we report a GWAS on the genetic basis of arterial stenosis as measured by cardiac catheterization in a Lebanese population. The locus of the phosphatase and actin regulator 1 gene (PHACTR1) showed association with coronary stenosis in a discovery experiment with genome wide data in 1,949 individuals (rs9349379, OR = 1.37, p = 1.57×10(-5)). The association was replicated in an additional 2,547 individuals (OR = 1.31, p = 8.85×10(-6)), leading to genome-wide significant association in a combined analysis (OR = 1.34, p = 8.02×10(-10)). Results from this GWAS support a central role of PHACTR1 in CAD susceptibility irrespective of lifestyle and ethnic divergences. This association provides a plausible component for understanding molecular mechanisms involved in the formation of stenosis in cardiac vessels and a potential drug target against CAD.

Background: A non-negligible proportion of patients with chest pain with negative cardiac troponin may harbor a disrupted coronary plaque. A marker of plaque rupture upstream from myocardial necrosis may help identify high-risk patients among this patient population. The purpose of this study was to investigate the correlation of plasma myeloperoxidase (MPO) concentration and angiographic coronary disease among patients with suspected troponin-negative coronary syndromes., Patients and Methods: Patients presenting with chest pain and negative cardiac troponin-T concentration and undergoing coronary angiography were enrolled in our study. Plasma MPO concentration was measured using a single blood sample collected prior to cardiac catheterization. The primary angiographic endpoint was the presence of at least one coronary stenosis causing a 70% or more diameter reduction; secondary endpoints were number of diseased vessels, presence of coronary thrombus, and lesion ulceration. The main clinical endpoint was coronary revascularization., Results: Three hundred and eighty-nine patients were enrolled. Presence of coronary stenosis causing a 70% or more diameter reduction increased with increasing quartiles of myeloperoxidase concentration (P<0.0001), as did the presence of coronary thrombus (P<0.0001) and plaque ulceration (P<0.0001). The need for percutaneous coronary revascularization also increased with increasing quartiles of systemic myeloperoxidase levels (P<0.0001). Coronary surgical revascularization did not differ among myeloperoxidase quartiles., Conclusion: Among patients with chest pain without troponin elevation, a single measurement of plasma MPO concentration can help identify patients with a higher risk of having significant coronary stenoses and high-risk angiographic features., (© 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins)

Background: Coronary artery disease (CAD) is a multifactorial disease with acquired and inherited components., Aim: We investigated the roles of family history and consanguinity on CAD risk and age at diagnosis in 4284 patients. The compounded impact of diabetes, hyperlipidemia, hypertension, smoking, and BMI, which are known CAD risk factors, on CAD risk and age at diagnosis was also explored., Methods: CAD was determined by cardiac catheterization. Logistic regression and stratification were performed to determine the impact of family history and consanguinity on risk and onset of CAD, controlling for diabetes, hyperlipidemia, hypertension, smoking, and BMI., Results: Family history of CAD and gender significantly increased the risk for young age at diagnosis of CAD (p<0.001). Consanguinity did not promote risk of CAD (p=0.38), but did affect age of disease diagnosis (p<0.001). The mean age at disease diagnosis was lowest, 54.8 years, when both family history of CAD and consanguinity were considered as unique risk factors for CAD, compared to 62.8 years for the no-risk-factor patient category (p<0.001)., Conclusions: Family history of CAD and smoking are strongly associated with young age at diagnosis. Furthermore, parental consanguinity in the presence of family history lowers the age of disease diagnosis significantly for CAD, emphasizing the role of strong genetic and cultural CAD modifiers. These findings highlight the increased role of genetic determinants of CAD in some population subgroups, and suggest that populations and family structure influence genetic heterogeneity between patients with CAD., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Coronary artery disease (CAD) is a complex disease with various components, genetic as well as environmental. Previous reports correlating ALOX5AP gene variants and CAD showed conflicting results depending on the population studied. In this study, we examined the contribution of ALOX5AP genetic predisposition to CAD in a group of CAD patients and controls carefully selected from the Lebanese population. We genotyped SNPs for ALOX5AP variants in 289 catheterized patients aged ≤52 years with >50% stenosis in at least one main coronary artery and 227 catheterized control subjects aged 60 years and above with 0% stenosis. Chi-square (χ (2)) tests and logistic regression showed no significant difference in the allele and genotype frequencies between the CAD or myocardial infarction (MI) cases and the healthy controls. Haplotype analysis using PHASE showed that the distribution of the risk haplotypes among cases and controls were not significantly different and had no attributable risk to CAD (P = 1.00 and P = 0.5, respectively) or MI (P = 0.2 and P = 0.5, respectively). Our data revealed that ALOX5AP gene variants are not predictors of CAD risk or MI risk among Lebanese patients.

Background: Mutations in genes regulating lipid metabolism, vasoactivity, and coagulation are important modulators of coronary artery disease (CAD)., Objective: This study investigated the association between allelic variants of the angiotensin converting enzyme (ACE), methytetrahydrofolate reductase, plasminogen activator inhibitor-1 and factor V genes and CAD., Methods: Clinical, biochemical, and angiographic information were collected from 300 patients who underwent cardiac catheterization and their DNA was genotyped by restriction fragment length polymorphism., Results: The frequency of the D allele of the ACE gene was significantly higher than the I allele in patients with more than 70% stenosis in any vessel. Among patients with more than 70% stenosis, carriers of the D allele were 2.8 times more likely to be males. The presence of the ACE I allele was negatively associated with CAD with (P=0.02 ,OR=0.38.), Conclusion: This study describes a protective role of the ACE I allele in individuals who may be at risk of developing CAD.

Early treatment of patients with acute coronary syndromes (ACS) is crucial to reduce morbidity and mortality. The purpose of this study was to examine delay in seeking care for ACS symptoms in a Lebanese sample and identify predictors of delay. Medical record reviews and interviews using the Response to Symptoms Questionnaire were conducted with 204 ACS patients in coronary care within 72 hours of admission. Median time from symptom onset to hospital arrival was 4.5 hours. Higher education, presence of dyspnea, intermittent symptoms, and waiting for symptoms to go away predicted longer delays, whereas intensity of symptoms and active response (going to the hospital) predicted shorter delays. The findings suggest lack of knowledge of ACS symptoms and the need for public education in this regard.

Background: Clopidogrel, in addition to aspirin, has become a common treatment of acute coronary syndrome and for stent thrombosis prevention, when given before percutaneous transluminal coronary angioplasty. However, some patients turn out to have surgical coronary artery disease and are sent for coronary artery bypass grafting (CABG) where the irreversible effect of aspirin and clopidogrel on platelet function becomes a concern. This study was conducted to evaluate the role of preoperative use of clopidogrel in bleeding complications after CABG., Material and Methods: A total of 462 patients who underwent CABG between 2001 and 2003 were studied as a retrospective cohort. Comparison was made between patients who had taken clopidogrel within 7 days of surgery (n=162), and those who were not exposed to clopidogrel (n=300). Chest tube output and bleeding index (a modified TIMI criteria), were the primary outcomes measured., Results: Our data showed that patients taking clopidogrel within 7 days of surgery have a higher bleeding index than those who were not exposed to the drug (p = 0.024). Similarly, chest tube output was significantly higher in those who were exposed to clopidogrel within 7 days compared to those not taking clopidogrel (p = 0.01). To further dissect this relationship, we divided our population into three categories. We found that patients taking clopidogrel within 3 days prior to CABG (immediate exposure) have a higher bleeding index and TIMI major bleeding than either patients taking the drug between 3 and 7 days (recent exposure) or patients not exposed to clopidogrel at all (p = 0.009 and 0.03 respectively for inter-groups comparison). The same was true for chest tube output (p = 0.05 and 0.01 respectively)., Conclusion: Clopidogrel increased the risk of post-CABG bleeding if taken within three days prior to surgery but not if taken before that.

Background: Coronary artery disease (CAD) is one of the major causes of morbidity and mortality in the world. The disease is determined by many risk factors such as age, gender, diabetes, dyslipidemia, smoking, as well as elevated serum levels of lipoprotein (a) (Lp(a)), homocysteine, C-reactive protein (CRP) and uric acid. In this study, we evaluated the association of biologic and metabolic parameters with CAD in a group of Lebanese patients., Methods: Three hundred patients were recruited for the study. Biologic and blood metabolic parameters were measured. Patients were then divided into 3 groups according to their catheterization result: 0% stenosis (controls), <50% stenosis and >or=50% stenosis., Results: Hyperlipidemias, CRP, homocysteine and uric acid levels in CAD patients were not different from those of the controls. However, age, elevated fasting blood glucose (FBG) and elevated serum Lp(a) levels were found to be strong independent predictors of CAD in our study population. Association with CAD was also shown for gender, hypertension, diabetes and family history of CAD., Conclusion: We report the importance of serum Lp(a) levels and FBG in the prediction and prevention of CAD in our population.

In this study, we measured the excretion rate of nicotine and its two major metabolites, cotinine and trans-3'-hydroxycotinine (THOC), in the urine of 25 healthy smokers and 15 smokers who underwent a coronary artery bypass surgery or coronary angioplasty. After 1 day of smoking cessation, urine samples were collected in the morning, before smoking two cigarettes, and then three times after smoking, approximately 4 h apart. The results show that (i) in healthy smokers, nicotine and its two major metabolites were present at high concentration in the first urine sample after smoking, (ii) in smokers with cardiovascular disease nicotine and cotinine were less excreted whereas THOC was more excreted, mainly in the second urine sample. We conclude that this shift in nicotine metabolism may contribute to smoking-induced cardiovascular disease.

The echocardiographic diagnosis of apical hypertrophic cardiomyopathy can be difficult in patients with poor acoustic windows. However, contrast-enhanced echocardiography can provide better images in these patients and lead to the correct diagnosis. We present a patient with apical hypertrophic cardiomyopathy who was diagnosed using contrast-enhanced echocardiography. The use of contrast-enhanced echocardiography for the diagnosis of apical hypertrophic cardiomyopathy in patients with poor acoustic windows is discussed and the experience in the literature reviewed.

Background: Coronary artery calcium score (CACS) correlates with atherosclerotic burden and predicts cardiac events. Most of the published data have been derived from the USA population., Objective: To study the prevalence of coronary calcium in an asymptomatic population from the eastern Mediterranean region and compare it to data obtained from a large population study in the USA., Results: A total of 1154 asymptomatic men and women from Lebanon underwent EBCT screening because of the presence of one or more CAD risk factors. Mean CACS as well as the percentile cut-points increased consistently with increasing age and, except for those above 74 years of age, were higher in men than women in each age stratum. Age, hypercholesterolemia, diabetes and smoking showed significant associations with CACS in men, while only age and hypercholesterolemia were significantly associated with CACS in women. Among men, the 75th and 90th percentile distributions were comparable to what is observed in developed countries such as the USA., Conclusion: Findings, from this first study in the region, suggest that despite a higher rate of diabetes and smokers in our study population, the CACS distribution in Lebanon is similar to that observed in the USA.

C-reactive protein (CRP) and complement proteins levels were determined in 20 patients with acute myocardial infarction (AMI) and 20 controls. Blood was obtained from all subjects at admission, 6 hr and 12 hr later. Serum CRP levels were determined by ELISA and complement proteins by radial immunodiffusion. A statistically significant elevation of the mean CRP level was obtained at 12 hr postadmission. The mean complement proteins levels were 16-49% higher in AMI patients than the controls. It appeared that the alternate pathway was activated initially, followed by activation of the classical pathway. The increased levels of CRP and complement proteins are suggestive of their involvement in AMI.

Type 1 diabetes (T1D) is a complex autoimmune disease. Several genetic loci have been implicated in the susceptibility to this illness. Evaluated was the role of the CTLA4 exon 1 A49G polymorphism and its role as a risk factor for T1D in our population. DNA from 190 patients with T1D and their families and 96 control individuals were genotyped for CTLA4 exon 1 polymorphism and human leukocyte antigen (HLA)-DQB1*0201 and *0302 haplotypes by polymerase chain reaction (PCR) amplification-restriction enzyme analysis and PCR amplification that used sequence-specific primers, respectively. Patients were nonobese and <26 years old. The CTLA4 G allele was found to be more frequently present in patients with T1D (32.4%) as compared with its frequency in control individuals (24.5%). The GG genotype was also significantly higher among patients (12.6%) than in controls (4.2%). chi(2) analysis and family-based association studies were performed and suggested the association of CTLA4 exon 1 G polymorphism with T1D (p = 0.0229). Furthermore, in HLA-DQB1*0201-positive patients with T1D, the GG and AA genotypes were higher and lower, respectively, than those found in control individuals. This study suggests that CTLA4 is a candidate susceptibility gene for T1D.

In the ischemic myocardium, reperfusion is necessary for the salvage of cells and cardiac function. However, reperfusion itself causes 'reperfusion injury', leading to the damage of myocardial cells. This is reduced by several interventions, as measured by the limitation of infarct size or reduction of arrhythmias. Pharmacological agents that protect against injury include Na(+)/H(+) exchanger inhibitors, antioxidants, calcium antagonists, renin-angiotensin system antagonists and adenosine. N-acetylcysteine, diltiazem, verapamil, enalaprilat and adenosine have all showed promising results in patients with acute myocardial infarction when given before reperfusion. Cariporide was beneficial when added to cardioplegia. However, their use in daily practice awaits results from large clinical trials.

We describe a case of pulmonary thromboembolism in a 61-year-old woman with beta-thalassemia intermedia and no other risk factors for thrombosis. Thromboembolism was documented by perfusion lung scan. We review the literature on this uncommon complication of thalassemia intermedia and discuss the pathogenesis and treatment options. A significant relationship between pulmonary thromboembolism and pulmonary hypertension in these patients was noted.