👤 Samer S Najjar

Lipoprotein(a) [Lp(a)] is a genetically determined, independent risk factor for atherosclerotic cardiovascular disease (ASCVD), unaffected by conventional lipid-lowering therapy. This study assessed the prevalence of elevated Lp(a) in a large, multiethnic cohort in Dubai, United Arab Emirates (UAE), analyzed its distribution across ethnicities, and evaluated its independence from low-density lipoprotein cholesterol (LDL-C). In a single-center multiethnic cohort study, 746 consecutive patients from Mediclinic Parkview Hospital, Dubai, were included. Serum Lp(a) was measured using a standardized immunoturbidometric assay. Positive Lp(a) was defined as ≥75 nmol/L. Levels were stratified by ethnic subgroups and categorized based on ESC/EAS quartiles and risk thresholds (≥105 nmol/L for high risk; >190 nmol/L for very high risk). The correlation between Lp(a) and directly measured LDL-C was assessed using Spearman's rank correlation in both patients receiving optimal lipid-lowering therapy and in those not receiving therapy. The prevalence of positive Lp(a) levels (≥75 nmol/L) was 30.2 %. At higher thresholds, 13.4 % had high-risk levels (≥105 nmol/L) and 9.9 % had very high-risk levels (>190 nmol/L). Ethnic variations were notable: South Asians (32.4 %) and White/Europeans (32.1 %) had the highest prevalence, while East Asians had the lowest (21.6 %) but the highest median level (200.5 nmol/L). Crucially, there was no correlation between Lp(a) and treated LDL-C in patients on optimal lipid-lowering therapy (Spearman's rho = 0.07, p = 0.38). We identified a high prevalence of elevated Lp(a) in a multiethnic cohort in Dubai, with nearly a quarter at high or severe risk. This risk is entirely independent of LDL-C, revealing a significant hidden burden not captured by standard lipid panels. These findings support integrating Lp(a) screening into regional cardiovascular prevention protocols. Show less

For the advancements of photoresponsive materials with tunable properties, the usage of multidimensional signals is desired. Using the polarization of the light in addition to the wavelength represents a further parameter to control the materials properties. Here, the first-time dynamic and reversible manipulation of the guest-host properties of a nanoporous material by linearly polarized light (LPL) is reported. The material is based on a metal-organic framework (MOF) with photoresponsive azobenzene side groups covalently connected to the MOF structure. The azobenzene moieties are reversibly reoriented by LPL, making the MOF structure and, thus, the pores anisotropic. As a result, the mobility of the guest molecules in the pores of the initially isotropic material becomes anisotropic, which can be dynamically controlled by the light polarization. The experiments by impedance spectroscopy are supported by molecular dynamics (MD) simulations. The study shows that the light polarization can be a further parameter to modify the material properties, allowing a more complex and more refined level of control for smart materials. Show less

Higher resting heart rate is associated with increased cardiovascular disease and mortality risk. Though heritable factors play a substantial role in population variation, little is known about specific genetic determinants. This knowledge can impact clinical care by identifying novel factors that influence pathologic heart rate states, modulate heart rate through cardiac structure and function or by improving our understanding of the physiology of heart rate regulation. To identify common genetic variants associated with heart rate, we performed a meta-analysis of 15 genome-wide association studies (GWAS), including 38,991 subjects of European ancestry, estimating the association between age-, sex- and body mass-adjusted RR interval (inverse heart rate) and approximately 2.5 million markers. Results with P < 5 × 10(-8) were considered genome-wide significant. We constructed regression models with multiple markers to assess whether results at less stringent thresholds were likely to be truly associated with RR interval. We identified six novel associations with resting heart rate at six loci: 6q22 near GJA1; 14q12 near MYH7; 12p12 near SOX5, c12orf67, BCAT1, LRMP and CASC1; 6q22 near SLC35F1, PLN and c6orf204; 7q22 near SLC12A9 and UfSp1; and 11q12 near FADS1. Associations at 6q22 400 kb away from GJA1, at 14q12 MYH6 and at 1q32 near CD34 identified in previously published GWAS were confirmed. In aggregate, these variants explain approximately 0.7% of RR interval variance. A multivariant regression model including 20 variants with P < 10(-5) increased the explained variance to 1.6%, suggesting that some loci falling short of genome-wide significance are likely truly associated. Future research is warranted to elucidate underlying mechanisms that may impact clinical care. Show less

To identify genetic variants influencing plasma lipid concentrations, we first used genotype imputation and meta-analysis to combine three genome-wide scans totaling 8,816 individuals and comprising 6,068 individuals specific to our study (1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables) and 2,758 individuals from the Diabetes Genetics Initiative, reported in a companion study in this issue. We subsequently examined promising signals in 11,569 additional individuals. Overall, we identify strongly associated variants in eleven loci previously implicated in lipid metabolism (ABCA1, the APOA5-APOA4-APOC3-APOA1 and APOE-APOC clusters, APOB, CETP, GCKR, LDLR, LPL, LIPC, LIPG and PCSK9) and also in several newly identified loci (near MVK-MMAB and GALNT2, with variants primarily associated with high-density lipoprotein (HDL) cholesterol; near SORT1, with variants primarily associated with low-density lipoprotein (LDL) cholesterol; near TRIB1, MLXIPL and ANGPTL3, with variants primarily associated with triglycerides; and a locus encompassing several genes near NCAN, with variants strongly associated with both triglycerides and LDL cholesterol). Notably, the 11 independent variants associated with increased LDL cholesterol concentrations in our study also showed increased frequency in a sample of coronary artery disease cases versus controls. Show less