Hypertension and type 2 diabetes (T2D) frequently coexist, but whether hypertension independently contributes to earlier diabetes onset beyond shared metabolic and genetic susceptibility remains incompletely understood. This study investigates the longitudinal relationship between hypertension and subsequent T2D risk using survival analysis and survival machine learning approaches. A matched cohort analysis was conducted using UK Biobank participants free of diabetes at baseline, and a 6-month lag period was applied to reduce reverse causation. Time-to-event analyses were performed using Cox proportional hazards models. Genetic susceptibility was evaluated using both a genome-wide polygenic risk score (PRS) and a targeted multi-variant score (TMS). Survival machine learning models including XGBoost, Random Survival Forests, and ridge-penalized Cox regression were evalueted under identical train/test splits. Additional robustness analyses incorporated antihypertensive medication classes, genetic principal components, broader hypertension phenotype definitions integrating blood pressure measurements and medication use, stricter baseline diabetes exclusion criteria, extended lag-period analyses, and time-stratified sensitivity analyses. The final multivariable matched analytic cohort included 76,439 participants (37,951 individuals with HTN and 38,488 matched controls). During follow-up, 4,315 incident T2D events occurred, including 3,571 among individuals with HTN and 744 among controls. Hypertension remained independently associated with T2D after adjustment for adiposity, lipid traits, statin use, antihypertensive medication classes, genetic principal components, and genetic susceptibility (HR 1.30, p < 0.001). Individuals with hypertension developed T2D earlier, with reduced diabetes-free survival over follow-up. Both PRS and TMS independently predicted T2D risk and demonstrated significant interactions with hypertension. Survival machine learning analyses showed progressive improvement in discrimination following incorporation of hypertension and genetic susceptibility, with XGBoost demonstrating the highest performance (C-index 0.823, 95

Background This study aimed to evaluate whether integrating clinical and genomic data improves the performance of machine learning (ML) models for predicting Type 2 Diabetes (T2D) risk. Methods Six models—Random Forest, Support Vector Machine, Linear Discriminant Analysis, Logistic Regression, Gradient Boosting Machine, and Decision Tree—were trained and tested on a discovery dataset (N=3,546) and validated in the UK Biobank (N=31,620). Model performance was assessed using clinical data alone, combined clinical and genomic data, and in age-specific groups (>55 and ≤55 years). Results The inclusion of genomic data modestly improved model performance across all algorithms in the discovery dataset. Clinical features such as family history of T2D and hypertension consistently ranked as top features. When SNPs were added, T2D-associated variants, including rs2943641 (IRS1), rs7903146 (TCF7L2), and rs7756992 (CDKAL1), emerged among the most important features, particularly in younger individuals. These findings demonstrate the translational potential of incorporating genomics for early risk identification. In the UK Biobank, all models achieved AUCs exceeding 91 % with combined clinical and genomic data. Performance was notably better among younger individuals (≤55 years), emphasizing the models’ potential for early detection. Integration of a polygenic risk score (PRS) further supported risk prediction, particularly in younger individuals, though incremental gains were modest. Conclusions While traditional clinical factors remained the strongest predictors of T2D risk, integration of genomic data produced a modest improvement in model performance, especially among younger adults. Validation across independent datasets confirmed the generalizability of these findings, underscoring the value of multi-dimensional risk-prediction models to refine T2D risk assessment.

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. One thousand nine hundred patients with severe and multivessel CAD (stenosis > 70

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.

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.

Background and objectives: High homocysteine levels are associated with increased risk of hy-pertension and stroke. Homocysteine is metabolized by the methylenetetrahydrofolate reductase (MTHFR). We aimed to investigate the levels of homocysteine and their association with hyper-tension, 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 pa-rameters. 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 & PLUSMN; 0.193 & mu;mol/L for hypertensive subjects compared to 11.9 & PLUSMN; 0.173 & mu;mol/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 medica-tion, and stroke risk among patients with the MTHFR T allele and the TT genotype. The associ-ation 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.

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.

Introduction: This study aims to investigate the association between epi- and pericardial adipose tissue deposits around the heart against patient body habitus when using cardiac computed tomography (CT). Methods: Ninety-two consecutive patients with suspected coronary artery disease underwent coronary CT angiography with quantitative cardiac and adipose tissue volume measurements. Body mass index (BMI), body surface area (BSA), thoracic circumference, anteroposterior diameter, cardiac and adipose tissue volumes were compared between genders by employing Pearson's correlation and results were considered statistically significant if p <= 0.05. Results: Statistically significant differences between genders were observed with males having a greater height (males 1.72 +/- 0.11), BMI (30.76 +/- 7.87 kg/m(2)), BSA (2.06 +/- 0.21 m(2)), thoracic circumference (1022.12 +/- 97.90 mm(2)), and pericardial adipose tissue volume (46.72 +/- 36.62 mm(3)) (p < 0.05). For men, for Group 1 (BMI <= 27) each of the measured volumes showed moderate correlation between pericardial adipose tissue and AP chest-diameter (r = 0.429, p < 0.05), whereas in Group 2 (27 < BMI <= 31.1), coronary artery volume had a strong association with the AP chest-diameter (r = 0.453, p < 0.05). Conclusion: BMI and thoracic circumference are closely related to variable epi- and pericardial adipose tissue volumes in both males and females during cardiac CT. Implications for practice: Quantification of epi- and pericardial adipose tissue deposits between males and females during cardiac CT may help further categorise coronary artery disease risk when including BMI and thoracic circumference for males and females. (C) 2021 The College of Radiographers. Published by Elsevier Ltd. All rights reserved.

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.

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.

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. 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. 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. 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.

Hypertrophic Cardiomyopathy (HCM) occurs in 1 of every 500 people and has a wide phenotypic variability. In the majority of cases, HCM is caused by known mutations in genes that code for sarcomere proteins. Although gene testing is widely available for HCM, knowing the phenotype caused by different gene mutations remains a challenging task. We recruited 28 families with HCM, of which 19 (67.8%) have at least one patient with pediatric onset. Index patients from 20 families received targeted sequencing for a panel of genes including TNNI3 , and 7 families received Sanger sequencing for the TNNI3 . We identified a missense mutation p.R21C in TNNI3 segregating with HCM in four families from South Lebanon. Through cascade screening, we identified 30 patients from the four families; twenty of them (67%) had a clinical diagnosis of HCM with a median age of 37 years, while 9 (30%), with a median age 21 years, had no evidence of HCM on echocardiography. An additional 27 members of the families had evidence of HCM, including 22 with SCD in the setting of no past medical history, and their carrier status for p.R21C was implied from the pedigrees. Survival analysis for 57 HCM patients with the mutation revealed a markedly decreased age at first adverse event as compared to 47 HCM patients with the MYBPC3 p.R502W mutation. Founder mutations in HCM that cause a severe phenotype are uncommon. The p.R21C mutation in TNNI3 is the first HCM mutation described in the Lebanese population and has a founder effect in South Lebanon. Early and more frequent screening with different imaging modalities as well as tailored management might be warranted for carriers of this mutation.

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.

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.

Hyperphosphatemic familial tumoral calcinosis (HFTC), secondary to fibroblast growth factor 23 (FGF23) gene mutation, is a rare genetic disorder characterized by recurrent calcified masses. We describe young Lebanese cousins presenting with HFTC, based on a retrospective chart review and a prospective case study. In addition, we present a comprehensive review on the topic, based on a literature search conducted in PubMed and Google Scholar, in 2014 and updated in December 2017. While the patients had the same previously reported FGF23 gene mutation (homozygous c.G367T variant in exon 3 leading to a missense mutation), they presented with variable severity and age of disease onset (at 4 years in patient 1 and at 23 years in patient 2). A review of the literature revealed several potential patho-physiologic pathways of HFTC clinical manifestations, some of which may be independent of hyperphosphatemia. Most available treatment options aim at reducing serum phosphate level, by stimulating renal excretion or by inhibiting intestinal absorption. HFTC is a challenging disease. While the available medical treatment has a limited and inconsistent effect on disease symptomatology, surgical resection of calcified masses remains the last resort. Research is needed to determine the safety and efficacy of FGF23 replacement or molecular therapy, targeting the specific genetic aberration. Hyperphosphatemic familial tumoral calcinosis is a rare genetic disorder characterized by recurrent calcified masses, in addition to other visceral, skeletal, and vascular manifestations. It remains a very challenging disease.

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).

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.

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.

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.