Metabolic dysfunction-associated fatty liver disease: current therapeutic strategies.

The definition of "Metabolic Associated Fatty Liver Disease - MAFLD" has replaced the previous definition of Nonalcoholic Fatty Liver Disease (NAFLD), because cardiometabolic criteria have been added for the prevention of cardiological risk in these patients. This definition leads to an in-depth study of the bidirectional relationships between hepatic steatosis, Type 2 Diabetes Mellitus (T2DM), Cardiovascular Disease (CVD) and/or their complications. Lifestyle modification, which includes correct nutrition combined with regular physical activity, represents the therapeutic cornerstone of MAFLD. When therapy is required, there is not clear accord on how to proceed in an optimal way with nutraceutical or pharmacological therapy. Numerous studies have attempted to identify nutraceuticals with a significant benefit on metabolic alterations and which contribute to the improvement of hepatic steatosis. Several evidences are supporting the use of silymarin, berberine, curcumin, Nigella sativa, Ascophyllum nodosum, and Fucus vesiculosus, vitamin E, coenzyme Q10 and Omega-3. However, more evidence regarding the long-term efficacy and safety of these compounds are required. There is numerous evidence that highlights the use of therapies such as incretins or the use of Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors or other similar therapies which, by assisting existing therapies for pathologies such as diabetes, hypertension, insulin resistance, have given a breakthrough in prevention and the reduction of cardiometabolic risk. This review gave an overview of the current therapeutic strategies that are expected to aid in the treatment and prevention of MAFLD.

The Gulf Achievement of Cholesterol Targets in Out-Patients Study (GULF ACTION): Design, Rationale, and Preliminary Results.

AIM: To assess the current dyslipidemia management in the Arabian Gulf region by describing the demographics, study design, and preliminary results of out-patients who achieved low-density lipoprotein cholesterol (LDL-C) goals at the time of the survey. BACKGROUND: The Arabian Gulf population is at high risk for atherosclerotic cardiovascular disease at younger ages. There is no up-to-date study regarding dyslipidemia management in this region, especially given the recent guideline-recommended LDL-C targets. OBJECTIVE: Up-to-date comprehensive assessment of the current dyslipidemia management in the Arabian Gulf region, particularly in view of the recent evidence of the additive beneficial effects of ezetimibe and proprotein convertase subtilisin/kexin-9 (PCSK-9) inhibitors on LDL-C levels and cardiovascular outcomes. METHODS: The Gulf Achievement of Cholesterol Targets in Out-Patients (GULF ACTION) is an ongoing national observational longitudinal registry of 3000 patients. In this study, adults ≥18 years on lipidlowering drugs for over three months from out-patients of five Gulf countries were enrolled between January 2020 and May 2022 with planned six-month and one-year follow-ups. RESULTS: Of the 1015 patients enrolled, 71% were male, aged 57.9±12 years. In addition, 68% had atherosclerotic cardiovascular disease (ASCVD), 25% of these patients achieved the LDL-C target, and 26% of the cohort were treated using combined lipid-lowering drugs, including statins. CONCLUSION: The preliminary results of this cohort revealed that only one-fourth of ASCVD patients achieved LDL-C targets. Therefore, GULF ACTION shall improve our understanding of current dyslipidemia management and "guideline gaps" in the Arabian Gulf region.

A Comprehensive Neuropsychological Study of Familial Hypercholesterolemia and Its Relationship with Psychosocial Functioning: A Biopsychosocial Approach.

BACKGROUND: Over the past few years, there has been an increasing interest in viewing the diagnosis of familial hypercholesterolemia (FH) through the lens of the biopsychosocial model. However, other than a few epidemiological surveys, there is a dearth of studies from emerging economies that have examined FH using the biological, psychological, and socio-environmental facets of the aforementioned model. AIM. The three aims of the current study were as follows: (i) to examine the psychosocial status among patients with genetically confirmed FH, (ii) to compare their intellectual capacity and cognitive outcomes with a reference group, and (iii) to examine the relationship between health literacy and cognitive functioning. METHOD: Consecutive FH patients referred to the lipid clinic at a tertiary care center for an expert opinion were recruited into this study conducted from September 2019 to March 2020. Information regarding psychosocial functioning, health literacy, quality of life, and affective ranges was surveyed. Indices of current reasoning ability and cognition (attention and concentration, memory, and executive functioning) were compared with a socio-demographically-matched reference group. The current hypothesis also explored the impact of FH on health literacy and cognition. RESULT: A total of 70 participants out of 106 (response rate: 66.0%) initially agreed to participate. However, 18 out of 70 dropped out of the study, yielding a final total of 52 FH patients. With 27 (51.9%) males and 25 (48.1%) females, the mean participant age stood at 37.2 years (SD = 9.2), ranging from 21 to 52 years of age. In the psychosocial data, thirty-two percent (n = 17) of them had anxiety (HADS ≥ 8), and twenty-five percent (n = 13) had depressive symptoms (HADS ≥ 8). The performance of the FH patients was significantly impaired compared to the control group on the indices of current reasoning ability and all domains of cognitive functioning. In the univariate analysis conducted to compare cognitive functioning with health literacy status, only indices of attention and concentration emerged as being significant. CONCLUSION: The current study indicates that the FH population is marked with impediments in biopsychosocial functioning, including indices tapping into the integrity of health literacy, quality of life, affective ranges, and higher functioning such as cognition and current reasoning ability when compared with a socio-demographically-matched reference group. The present results support the hypothesis that chronic diseases vis-à-vis the sequelae of coronary artery disease can potentially impede biopsychosocial functioning.

The Genetic Spectrum of Familial Hypertriglyceridemia in Oman.

Familial hypertriglyceridemia (F-HTG) is an autosomal disorder that causes severe elevation of serum triglyceride levels. It is caused by genetic alterations in LPL, APOC2, APOA5, LMF1, and GPIHBP1 genes. The mutation spectrum of F-HTG in Arabic populations is limited. Here, we report the genetic spectrum of six families of F-HTG of Arab ancestry in Oman. Methods: six Omani families affected with triglyceride levels >11.2 mmol/L were included in this study. Ampli-Seq sequencing of the selected gene panels was performed. Whole-exome sequencing and copy number variant analysis were also performed in cases with negative exome results. Three novel pathogenic missense variants in the LPL gene were identified, p.M328T, p.H229L, and p.S286G, along with a novel splice variant c.1322+15T > G. The LPL p.H229L variant existed in double heterozygous mutation with the APOA5 gene p.V153M variant. One family had a homozygous mutation in the LMF1 gene (c.G107A; p.G36D) and a heterozygous mutation in the LPL gene (c.G106A; p.D36N). All affected subjects did not have a serum deficiency of LPL protein. Genetic analysis in one family did not show any pathogenic variants even after whole-exome sequencing. These novel LPL and APOA5 mutations are not reported in other ethnic groups. This suggests that patients with F-HTG in Oman have a founder effect and are genetically unique. This warrants further analysis of patients of F-HTG in the Middle East for preventative and counseling purposes to limit the spread of the disease in a population of high consanguinity.

The Achievement of Non-high-density Lipoprotein Cholesterol Target in Patients with Very High Atherosclerotic Cardiovascular Disease Risk Stratified by Triglyceride Levels Despite Statin-controlled Low-density Lipoprotein Cholesterol.

Objectives: We sought to estimate the percentage achievements of non-high-density lipoprotein cholesterol (non-HDL-C) target in patients with very high atheroscleroticcardiovascular diseases (ASCVD) risk stratified by triglyceride (TG) levels despite statin-controlled low-density lipoprotein cholesterol (LDL-C) in the Centralized Pan-Middle East Survey on the under treatment of hypercholesterolemia. Methods: The non-HDL-C target achievement in patients with diabetes mellites (DM) and patients with established ASCVD was defined according to European Society of Cardiology and European Atherosclerosis Society 2019 guidelines for managing dyslipidemia. Patients were stratified to controlled LDL-C defined as < 70 mg/dL (< 1.8 mmol/L) with normal TG < 150 mg/dL (< 1.7 mmol/L) and high TG between 150-400 mg/dL (1.7-4.5 mmol/L). Results: The mean age of our cohort was 58.0±11.0 years, 6.8% (n = 717) were male, 9.7% (104) were smokers, and 48.4% (n = 518) had body mass index of ≥ 30 kg/m2. Those with high TG levels male (76.5% vs. 63.8%; p < 0.001), smokers (16.1% vs. 7.7%; p < 0.001), have metabolic syndrome (77.6% vs. 17.1%; p < 0.001), and low HDL-C levels (79.2% vs. 49.4%; p < 0.001). The majority (93.9%, n = 1008) were on statins (atorvastatin and rosuvastatin) with only 2.2% (n = 24) on the combined statins plus fenofibrate/gemfibrozil. Only 27.4% (n = 294) of patients had non-HDL-C goal attainment. Goal attainment rates in patients with diabetes (3.1% vs. 34,4%; p < 0.001), coronary artery disease (CAD) (2.4% vs. 37.9%; p < 0.001), diabetes plus CAD (0% vs. 40.0%; p < 0.001), and CVD (0% vs. 30.0%; p = 0.048) were significantly lower in those with higher TG levels. Conclusions: A large proportion of statin-controlled LDL-C diabetic patients and patients with established ASCVD with high TGs did not achieve the non-HDL-C target. Our study did not demonstrate an association between ASCVD and high TG levels; and therefore, a follow-up study is highly required to assess long-term ASCVD outcomes in this cohort.

Antihypertensive Drugs and Perinatal Outcomes in Hypertensive Women Attending a Specialized Tertiary Hospital.

Objectives: We sought to identify the most commonly used antihypertensive medications in pregnant women and to determine the impact of these medications on perinatal (maternal and fetal) outcomes. Methods: The medical records of 484 hypertensive pregnant women who attended a tertiary university hospital during the study period were retrospectively evaluated for eligibility. Singleton pregnancies of women on antihypertensive medications and who delivered in the hospital were included in the study. Results: A total of 210 women (mean age of 32.4±5.6 years and mean body mass index of 34.0±8.1 kg/m2) were eligible for inclusion in the study. The most prevalent subtype of hypertension was preeclampsia (41.4%). Low birth weight (LBW), preterm delivery (PTD), intrauterine growth restriction (IUGR), small for gestational age (SGA), respiratory distress syndrome, and neonatal care unit admissions were significantly higher in women with preeclampsia than in the women with other types of hypertension. Labetalol was the most commonly prescribed antihypertensive drug. There were 101 (48.1%) women on combined therapy. LBW, PTD, IUGR, SGA, respiratory distress syndrome, absent end diastolic flow, neonatal care unit admission, preeclampsia, and high dependency unit admissions of mothers were significantly higher in the women who received combined therapy. Conclusions: Labetalol was the most commonly prescribed antihypertensive drug in this cohort, and women on combined antihypertensive medications had significantly higher maternal and fetal complications. A larger prospective study including hypertensive women with or without antihypertensive medications in more than one center is needed to evaluate the effect of these drugs on perinatal outcomes.

Metabolic Side Effects of Olanzapine in Patients With Psychotic Disorders in Oman: A Retrospective Cohort Study.

We evaluated the impact of olanzapine on metabolic changes in patients with psychotic disorders. This was a retrospective cohort study involving patients prescribed olanzapine and attending Sultan Qaboos University Hospital (Muscat, Oman). Patients were followed up retrospectively from March 2006 until April 2021. Cardiovascular treatment targets were evaluated as per the 2019 European Society of Cardiology guidelines. We enrolled 253 patients (mean age: 40±17 years). Olanzapine monotherapy was associated with increased body weight (+8 kg; 95% confidence interval (CI): 6-9; P < .001), body mass index (+3 kg/m2; 95% CI: 2-4; P < .001), total cholesterol (+.4 mmol/L; 95% CI: .3-.5; P < .001), low-density lipoprotein cholesterol (LDL-C) (+.3 mmol/L; 95% CI: .1-.4; P < .001), fasting triglycerides (+.2 mmol/L; 95% CI: .1-.3; P<.001), fasting glucose (+.6 mmol/L; 95% CI: .4-.7; P< .001), HbA1c (+.3%; 95% CI: .2-.4; P < .001), systolic blood pressure (BP) (+9 mmHg; 95% CI: 6-12; P < .001) and diastolic BP (+4 mmHg; 95% CI: 2-6; P < .001) levels. Cardiovascular therapeutic goals were attained in 38% (n = 97), 61% (n = 154), 71% (n = 180), and 59% (n = 150) for LDL-C, non-high-density lipoprotein cholesterol, triglycerides, and BP, respectively. Olanzapine was associated with adverse metabolic changes. Therefore, many patients were not at their target cardiovascular treatment goals.

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.

Clinical and Genetic Characteristics of Familial Hypercholesterolemia at Sultan Qaboos University Hospital in Oman.

OBJECTIVES: We sought to describe the clinical and genetic characteristics of patients with familial hypercholesterolemia (FH) that presented to the lipid clinic at Sultan Qaboos University Hospital, Muscat, Oman. METHODS: Patients who presented with high low-density lipoprotein cholesterol (LDL-C) levels (> 189.0 mg/dL or 4.9 mmol/L) were recruited to the study. FH was diagnosed according to the Dutch Lipid Clinic Network criteria. Analyses were performed using univariate statistics. RESULTS: The study enrolled 450 patients with a mean age of 48.0±12.0 years, 56.0% (n = 252) were males and 11.3% (n = 51) were smokers. At admission, the proportion of 'probable/definite', 'possible', and 'unlikely' FH were 27.6% (n = 124), 70.0% (n = 315), and 2.4% (n = 11), respectively. Overall, 26.0% (n = 117) of patients had hypertension, 22.4% (n = 101) had a history of coronary artery disease, and 17.3% (n = 78) had diabetes mellitus. Those with 'probable/definite' FH were more likely to be prescribed high-intensity statin therapy (75.8% vs. 54.5%; p < 0.001) and statin ezetimibe combination (50.8% vs. 27.3%; p < 0.001) when compared to the 'unlikely' FH cohort. Additionally, those with very high atherosclerotic vascular disease (ASCVD) risk were also associated with high-intensity statin therapy (54.7% vs. 42.7%; p = 0.006) and statin ezetimibe combination (26.4% vs. 17.2%; p = 0.023). Patients with 'probable/definite' FH were less likely to achieve their LDL-C goal attainment compared to those with 'unlikely' FH (13.0% vs. 57.1%; p < 0.001). Furthermore, those with very high ASCVD risk were less likely to achieve their LDL-C goals compared to the high ASCVD risk cohort (9.6% vs. 32.0%; p < 0.001). CONCLUSIONS: FH patients are underdiagnosed, undertreated, and less likely to attain their LDL-C goals in Oman.

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.

Aortic Calcification Progression in Heterozygote Familial Hypercholesterolemia.

BACKGROUND: Patients with homozygous and heterozygous familial hypercholesterolemia (HeFH) develop severe aortic calcifications in an age- and gene dosage-dependent manner. The purpose of this study was to determine the rate of progression of aortic calcification in patients with HeFH. METHODS: We performed thoracoabdominal computed tomography scans and quantified aortic calcium (AoCa) score in 16 HeFH patients, all with the null low-density lipoprotein (LDL) receptor DEL15Kb mutation. Patients (12 men, 4 women) were rescanned an average of 8.2 ± 0.8 years after the first scan. RESULTS: Mean LDL cholesterol (LDL-C) during treatment was 2.53 mmol/L; all patients were receiving high-dose statin/ezetimibe; 5 of 16 were receiving evolocumab. Baseline LDL-C was 7.6 ± 1.3 mmol/L. Aortic calcifications increased in all patients in an exponential fashion with respect to age. Age was the strongest correlate of AoCa score. Cholesterol, LDL-C, or age × cholesterol did not correlate with AoCa score or its progression. Control patients (n = 31; 8 male, 23 female; mean age 61 ± 11 years) who underwent virtual colonoscopy were rescanned over the same period and showed an abdominal AoCa score of 1472 ± 2489 compared with 7916 ± 7060 Agatston U (P < 0.001) in patients with HeFH during treatment (mean age, 60 ± 14 years). The rate of progression was 159 vs 312 Agatston U/y in control participants vs those with HeFH. CONCLUSIONS: HeFH patients exhibit accelerated aortic calcification that increases exponentially with age. LDL-C at baseline or during treatment seems to have little effect on the rate of progression of AoCa score. Strategies to prevent aortic calcifications with statins have not met with clinical success and novel approaches are required; statins might also contribute to the process of arterial calcification.

Gender Disparity in Lipid Target Achievements in High and Very High Atherosclerotic Cardiovascular Disease Risk Patients in the Arabian Gulf.

BACKGROUND: Few studies assessed gender disparity in lipid goal attainment in the Arabian Gulf. Hence, we estimated gender gaps in lipid target achievements among patients at high and very high atherosclerotic cardiovascular disease (ASCVD) risk in the Centralized Pan-Middle East Survey on the undertreatment of hypercholesterolemia (CEPHEUS). METHODS: The study (conducted between November 22, 2009 and July 7, 2010) included 4,384 patients (≥18 years) on lipid lowering drugs at high and very ASCVD risk status from outpatient clinics of 177 specialists and primary care physicians in 6 Arabian Gulf countries. RESULTS: The overall mean age was 57±11 years and 40% (n=1763) were women. Women were more likely to have diabetes mellitus (84 vs 71%; p <0.001) and metabolic syndrome (49 vs 35%; p <0.001) compared with males. Women were less likely to achieve their low-density lipoprotein cholesterol (LDLC) (28 vs 32%; p = 0.002), high-density lipoprotein cholesterol (HDL-C) (42 vs 50%; p <0.001), and apolipoprotein B (Apo B) (38 vs 42%; p = 0.015) targets compared with men. In the very high ASCVD risk cohort, women were significantly less likely to achieve their LDL-C (20 vs 30%; p <0.001), non- HDL-C (34 vs 39%; p = 0.001) and Apo B (34 vs 41%; p <0.001) therapeutic targets compared with men. CONCLUSION: Women in the Arabian Gulf were less likely to achieve their lipid targets than men. The difference was more significant in the very high ASCVD risk group.

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

BACKGROUND: Plasma lipid disorders are key risk factors for the development of atherosclerotic cardiovascular disease (ASCVD) and are prevalent in the Middle East, with rates increasing in recent decades. Despite this, no region-specific guidelines for managing plasma lipids exist and there is a lack of use of guidelines developed in other regions. METHODS: A multidisciplinary panel of regional experts was convened to develop consensus clinical recommendations for the management of plasma lipids in the Middle East. The panel considered existing international guidelines and regional clinical experience to develop recommendations. RESULTS: The panel's recommendations include plasma lipid screening, ASCVD risk calculation and treatment considerations. The panel recommend that plasma lipid levels should be measured in all at-risk patients and at regular intervals in all adults from the age of 20years. A scoring system should be used to calculate ASCVD risk that includes known lipid and non-lipid risk factors. Primary treatment targets include low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol. Lifestyle modifications should be first-line treatment for all patients; the first-line pharmacological treatment targeting plasma lipids in patients at moderate-to-high risk of ASCVD is statin therapy, with a number of adjunctive or second-line agents available. 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. CONCLUSIONS: These 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.

Dyslipidaemia in the Middle East: Current status and a call for action.

The increase in the cardiovascular disease (CVD)-associated mortality rate in the Middle East (ME) is among the highest in the world. The aim of this article is to review the current prevalence of dyslipidaemia and known gaps in its management in the ME region, and to propose initiatives to address the burden of dyslipidaemia. Published literature on the epidemiology of dyslipidaemia in the ME region was presented and discussed at an expert meeting that provided the basis of this review article. The high prevalence of metabolic syndrome, diabetes, familial hypercholesterolaemia (FH) and consanguineous marriages, in the ME region, results in a pattern of dyslipidaemia (low high-density lipoprotein cholesterol and high triglycerides) that is different from many other regions of the world. Early prevention and control of dyslipidaemia is of paramount importance to reduce the risk of developing CVD. Education of the public and healthcare professionals and developing preventive programs, FH registries and regional guidelines on dyslipidaemia are the keys to dyslipidaemia management in the ME region.

Impact of metabolic syndrome on lipid target achievements in the Arabian Gulf: findings from the CEPHEUS study.

BACKGROUND: The aim of this study was to determine the impact of metabolic syndrome (MetS) on lipid target achievements in the Arabian Gulf. METHODS: The centralized pan-middle east survey on the undertreatment of hypercholesterolemia (CEPHEUS) included 4171 high and very high atherosclerotic cardiovascular disease (ASCVD) risk patients from six Arabian Gulf countries. Analyses were performed using univariate statistics. RESULTS: The overall mean age was 57 ± 11 years, 41 % were females and 71 % had MetS. MetS patients were less likely to attain their HDL-C (34 vs. 79 %; P < 0.001), LDL-C (27 vs. 37 %; P < 0.001), non HDL-C (35 vs. 55 %; P < 0.001) and Apo B (35 vs. 54 %; P < 0.001) compared to those without MetS. Within the MetS cohort, those with very high ASCVD risk were less likely to attain their lipid targets compared to those with high ASCVD risk [HDL-C (32 vs. 41 %; P < 0.001), LDL-C (24 vs. 43 %; P < 0.001), non HDL-C (32 vs. 51 %; P < 0.001) and Apo B (33 vs. 40 %; P = 0.001)]. In those with MetS and very high ASCVD risk status, females were less likely to attain their HDL-C (27 vs. 36 %; P < 0.001), LDL-C (19 vs. 27 %; P < 0.001) and Apo B (30 vs. 35 %; P = 0.009) compared to males. CONCLUSIONS: MetS was associated with low lipid therapeutic targets. Women and those with very high ASCVD risk were also less likely to attain their lipid targets in the Arabian Gulf.

Non-high-density lipoprotein cholesterol target achievement in patients on lipid-lowering drugs and stratified by triglyceride levels in the Arabian Gulf.

BACKGROUND: Atherogenic dyslipidemia is highly prevalent in the Arabian Gulf. Non-high-density lipoprotein cholesterol (non-HDL-C) reduction has been proposed as an additional goal to low-density lipoprotein cholesterol (LDL-C) lowering to prevent atherosclerotic cardiovascular disease (ASCVD). Data on non-HDL-C goal attainment in patients with high triglycerides (TGs) on lipid-lowering drugs (LLDs) in the region is scarce. OBJECTIVE: Evaluate non-HDL-C target attainment according to the National Lipid Association in patients on LLDs stratified by TG (<150 [1.69], 150-200 [1.69-2.26], >200 [2.26] mg/dL [mmol/L]) levels in the Arabian Gulf. METHODS: Overall, 4383 patients on LLD treatment from 6 Middle Eastern countries participating in the Centralized Pan-Middle East Survey on the Undertreatment of Hypercholesterolemia study were evaluated. Patients were classified according to TG levels and ASCVD risk. RESULTS: The overall non-HDL-C goal attainment was 41% of the subjects. Non-HDL-C goal was less likely attained in patients with high TGs (12% vs 27% vs 55%; P < .001). Very high ASCVD risk patients with high TGs attained less their non-HDL-C targets compared with those with lower TG levels (8% vs 23% vs 51%; P < .001). Similarly, high ASCVD risk patients with high TGs also failed more in attaining non-HDL-C targets compared with those with lower TGs (26% vs 42% vs 69%; P < .001). In addition, those with high TG also succeeded less in attaining LDL-C and apolipoprotein B goals (P < .001). CONCLUSIONS: A large proportion of very high and high ASCVD patients on LLDs in the Arabian Gulf are not at recommended non-HDL-C targets and hence remain at a substantial residual risk.

Nutraceuticals as Lipid-Lowering Treatment in Pregnancy and Their Effects on the Metabolic Syndrome.

Maternal nutrition and lifestyle before and during pregnancy influence both mother and offspring's health and can be correlated with the metabolic syndrome in later life. Findings from animal and human studies indicate that nutrition during pregnancy has an important role in microbiological, metabolic, physiologic and immunologic development and homeostasis. A low nutritional intake in early pregnancy may represent a risk for adverse effects during pregnancy as well as on birth outcome. It seems that dietary supplementation with probiotics in perinatal period may represent safe and practical approach in dealing with the most common adverse pregnancy outcomes such as obesity and gestational diabetes. The SPRING (Study of Probiotics in the prevention of Gestational diabetes) will give important answers about potential benefits of probiotics in pregnant women who are obese and overweight and otherwise at the high risk for complications during pregnancy. Fish oil supplementation during the last trimester of pregnancy showed no effects on plasma lipids and lipoproteins in offspring, as well as on their adiposity. The effect of hypercholesterolemia during pregnancy on both mothers and child needs to be further investigated as it could have a biological role. The guidelines for the eventual clinical approach currently do not exist. Potential benefits of nutraceuticals on several metabolic parameters have been suggested. Limited evidence does not allow to draw final conclusions on preventive health strategies and dietary patterns that should be promoted during pregnancy. Further prospective and intervention studies are needed to establish it. Healthy lifestyle and dietary advice with appropriate supplements usage should be considered.

Incretins, Pregnancy, and Gestational Diabetes.

The number of pregnant women affected by gestational diabetes mellitus (GDM) is increasing among Caucasians, and East Asians. GDM also increases the risk for later advent of type 2 diabetes mellitus (T2DM), obesity, and cardiovascular disease in both women and their offspring. The underlying mechanism of GDM is not fully elucidated. Incretins such as glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), have been suggested to have a role in maternal metabolism and weight as well as fetal growth. These hormones might be implicated in mechanisms that compensate for the increment in glycemia and insulin resistance seen during pregnancy, while other factors, such as heredity, environment and lifestyle, but also different race/ethnic background might also lead to the comorbid health problems. Some studies indicate that pregnancy is associated with a diminished GLP-1 response which is more prominently evident in women with GDM and normalizes after delivery. Postprandial GIP level seems to be unaffected by pregnancy, despite its increased level in GDM. On the other hand, the reduced incretin effect observed in GDM may represent a risk factor for obesity, T2DM and metabolic disorders even in the offspring of these women. Further investigations are needed to establish the exact role of incretins in pregnancy and gestational glucose intolerance.