Non-HDL-cholesterol in dyslipidemia: Review of the state-of-the-art literature and outlook.

Dyslipidemia refers to unhealthy changes in blood lipid composition and is a risk factor for atherosclerotic cardiovascular diseases (ASCVD). Usually, low-density lipoprotein-cholesterol (LDL-C) is the primary goal for dyslipidemia management. However, non-high-density lipoprotein cholesterol (non-HDL-C) has gained attention as an alternative, reliable goal. It encompasses all plasma lipoproteins like LDL, triglyceride-rich lipoproteins (TRL), TRL-remnants, and lipoprotein a [Lp(a)] except high-density lipoproteins (HDL). In addition to LDL-C, several other constituents of non-HDL-C have been reported to be atherogenic, aiding the pathophysiology of atherosclerosis. They are acknowledged as contributors to residual ASCVD risk that exists in patients on statin therapy with controlled LDL-C levels. Therefore, non-HDL-C is now considered an independent risk factor or predictor for CVD. The popularity of non-HDL-C is attributed to its ease of estimation and non-dependency on fasting status. It is also better at predicting ASCVD risk in patients on statin therapy, and/or in those with obesity, diabetes, and metabolic disorders. In addition, large follow-up studies have reported that individuals with higher baseline non-HDL-C at a younger age (<45 years) were more prone to adverse CVD events at an older age, suggesting a predictive ability of non-HDL-C over the long term. Consequently, non-HDL-C is recommended as a secondary goal for dyslipidemia management by most international guidelines. Intriguingly, geographical patterns in recent epidemiological studies showed remarkably high non-HDL-C attributable mortality in high-risk countries. This review highlights the independent role of non-HDL-C in ASCVD pathogenesis and prognosis. In addition, the need for a country-specific approach to dyslipidemia management at the community/population level is discussed. Overall, non-HDL-C can become a co-primary or primary goal in dyslipidemia management.

Consensus clinical recommendations for the management of plasma lipid disorders in the Middle East: 2021 update.

BACKGROUND AND AIMS: Disorders of plasma lipids remain key risk factors for the development of atherosclerotic cardiovascular disease (ASCVD) in the Middle East and are estimated to increase more dramatically in the next decade than in any other global region except Africa. This statement is an update to the 2016 consensus clinical recommendations for the management of plasma lipid disorders in the Middle East, following the evaluation of newer cholesterol-lowering agents in randomised controlled cardiovascular outcome trials, as well as the publication of revised international guidelines. METHODS: A multidisciplinary panel of regional experts was convened to update the consensus clinical recommendations for the management of plasma lipids in the Middle East. The recommendations constructed in 2016 were reviewed against emerging research since publication. RESULTS: Newly developed Middle East ASCVD risk categories were established using the multiple risk group categories from the recently updated international guidelines and the epidemiological evidence from the Gulf Region. These consensus recommendations support a more intensive reduction of LDL-C across cardiovascular risk categories. Alongside low-density lipoprotein cholesterol, we recommend non-high-density lipoprotein cholesterol as a primary treatment target. Lifestyle modifications remain the first-line treatment recommendation for all patients. The first-line pharmacological treatment in patients with dyslipidaemia is statin therapy, with a number of second-line agents available. The selection of a second lipid-lowering agent for combination therapy with statin should be based on the lipid-lowering target of the patient. Guidance is also provided on the management of underlying conditions and special populations; of particular pertinence in the region are familial hypercholesterolaemia, diabetes and metabolic dyslipidaemia. New therapies have emerged from research that found positive outcomes in reducing low-density lipoprotein cholesterol levels. The initial results of these newly researched drugs strongly indicate their inclusion as future therapies in dyslipidaemia management in the Middle East. CONCLUSIONS: These updated consensus clinical recommendations provide practicing clinicians with comprehensive, region-specific guidance to improve the detection and management of plasma lipid disorders in patients in the Middle East.

Familial Hypercholesterolemia in the Arabian Gulf Region: Clinical results of the Gulf FH Registry.

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is a common autosomal dominant disorder that can result in premature atherosclerotic cardiovascular disease (ASCVD). Limited data are available worldwide about the prevalence and management of FH. Here, we aimed to estimate the prevalence and management of patients with FH in five Arabian Gulf countries (Saudi Arabia, Oman, United Arab Emirates, Kuwait, and Bahrain). METHODS: The multicentre, multinational Gulf FH registry included adults (≥18 years old) recruited from outpatient clinics in 14 tertiary-care centres across five Arabian Gulf countries over the last five years. The Gulf FH registry had four phases: 1- screening, 2- classification based on the Dutch Lipid Clinic Network, 3- genetic testing, and 4- follow-up. RESULTS: Among 34,366 screened patient records, 3713 patients had suspected FH (mean age: 49±15 years; 52% women) and 306 patients had definite or probable FH. Thus, the estimated FH prevalence was 0.9% (1:112). Treatments included high-intensity statin therapy (34%), ezetimibe (10%), and proprotein convertase subtilisin/kexin type 9 inhibitors (0.4%). Targets for low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol were achieved by 12% and 30%, respectively, of patients at high ASCVD risk, and by 3% and 6%, respectively, of patients at very high ASCVD risk (p <0.001; for both comparisons). CONCLUSIONS: This snap-shot study was the first to show the high estimated prevalence of FH in the Arabian Gulf region (about 3-fold the estimated prevalence worldwide), and is a "call-to-action" for further confirmation in future population studies. The small proportions of patients that achieved target LDL-C values implied that health care policies need to implement nation-wide screening, raise FH awareness, and improve management strategies for FH.

The Gulf Familial Hypercholesterolemia Registry (Gulf FH): Design, Rationale and Preliminary Results.

AIM: To determine the prevalence, genetic characteristics, current management and outcomes of familial hypercholesterolaemia (FH) in the Gulf region. METHODS: Adult (18-70 years) FH patients were recruited from 9 hospitals and centres across 5 Arabian Gulf countries. The study was divided into 4 phases and included patients from 3 different categories. In phase 1, suspected FH patients (category 1) were collected according to the lipid profile and clinical data obtained through hospital record systems. In phase 2, patients from category 2 (patients with a previous clinical diagnosis of FH) and category 1 were stratified into definitive, probable and possible FH according to the Dutch Lipid Clinic Network criteria. In phase 3, 500 patients with definitive and probable FH from categories 1 and 2 will undergo genetic testing for 4 common FH genes. In phase 4, these 500 patients with another 100 patients from category 3 (patients with previous genetic diagnosis of FH) will be followed for 1 year to evaluate clinical management and cardiovascular outcomes. The Gulf FH cohort was screened from a total of 34,366 patients attending out-patient clinics. RESULTS: The final Gulf FH cohort consisted of 3,317 patients (mean age: 47±12 years, 54% females). The number of patients with definitive FH is 203. In this initial phase of the study, the prevalence of (probable and definite) FH is 1/232. CONCLUSION: The prevalence of FH in the adult population of the Arabian Gulf region is high. The Gulf FH registry, a first-of-a-kind multi-national study in the Middle East region, will help in improving underdiagnosis and undertreatment of FH in the region.

Peripheral blood microRNA-15a is a potential biomarker for type 2 diabetes mellitus and pre-diabetes.

MicroRNAs (miRNAs) are small non-coding RNAs that function as crucial regulators of gene expression. Recently, dysregulation of miRNA expression in the blood has been demonstrated to be associated with various diseases, including type 2 diabetes mellitus (T2D), suggesting a potential for their use as biomarkers of disease prognosis. The present study examined the expression levels of T2D­associated miR­15a in peripheral whole blood samples from patients with T2D, pre­diabetes individuals exhibiting impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), as well as healthy control subjects, in order to investigate the potential of peripheral blood plasma miR­15a as a biomarker for the prediction of T2D and pre­diabetes. The present study included 24 patients with T2D, 22 IFG/IGT individuals and 24 healthy controls. The expression levels of miR­15a were analyzed by reverse transcription-quantitative polymerase chain reaction. The results indicated that the peripheral blood miR­15a expression levels were significantly decreased in patients with T2D and IFG/IGT individuals, compared with healthy control subjects (P<0.05). As determined by multivariate logistic regression analysis, lower miR­15a expression was significantly associated with T2D (odds ratio [OR]; 95% confidence interval [CI]: 0.51; 0.16­0.73, respectively; P<0.05) and pre­diabetes (OR; 95% CI: 0.56; 0.23­0.79, respectively; P<0.05). This association remained statistically significant following adjustment for age, body mass index and hypertension, as well as other biochemical indicators. Furthermore, a receiver operating characteristic analysis revealed that blood miR­15a distinguished patients with T2D and IFG/IGT individuals from healthy controls (area under the curves; 95% CI: 0.864; 0.751­0.977 and 95% CI: 0.852; 0.752­0.953, respectively). These results demonstrated that peripheral blood miR­15a expression levels were significantly lower in patients with T2D and IFG/IGT individuals, compared with healthy individuals. Thus, miR­15a in peripheral whole blood may serve as a potential biomarker for T2D and pre-diabetes.