scholarly journals Low Detection Rates of Genetic FH in Cohort of Patients With Severe Hypercholesterolemia in the United Arabic Emirates

2022 ◽  
Vol 12 ◽  
Author(s):  
Antoine Rimbert ◽  
Hinda Daggag ◽  
Peter Lansberg ◽  
Adam Buckley ◽  
Martijn Viel ◽  
...  

Background: Programs to screen for Familial hypercholesterolemia (FH) are conducted worldwide. In Western societies, these programs have been shown to be cost-effective with hit/detection rates of 1 in 217–250. Thus far, there is no published data on genetic FH in the Gulf region. Using United Arab Emirates as a proxy for the Gulf region, we assessed the prevalence of genetically confirmed FH in the Emirati population sample.Materials and Methods: We recruited 229 patients with LDL-C >95th percentile and employed a customized next generation sequencing pipeline to screen canonical FH genes (LDLR, APOB, PCSK9, LDLRAP1).Results: Participants were characterized by mean total cholesterol and low-density lipoprotein cholesterol (LDL-c) of 6.3 ± 1.1 and 4.7 ± 1.1 mmol/L respectively. Ninety-six percent of the participants were using lipid-lowering medication with mean corrected LDL-c values of 10.0 ± 3.0 mmol/L 15 out of 229 participants were found to suffer from genetically confirmed FH. Carriers of causal genetic variants for FH had higher on-treatment LDL-c compared to those without causal variants (5.7 ± 1.5 vs 4.7 ± 1.0; p = 3.7E-04). The groups did not differ regarding high-density lipoprotein cholesterol, triglycerides, body mass index, blood pressure, glucose, and glycated haemoglobin.Conclusion: This study reveals a low 7% prevalence of genetic FH in Emiratis with marked hypercholesterolemia as determined by correcting LDL-c for the use of lipid-lowering treatment. The portfolio of mutations identified is, to a large extent, unique and includes gene duplications. Our findings warrant further studies into origins of hypercholesterolemia in these patients. This is further supported by the fact that these patients are also characterized by high prevalence of type 2 diabetes (42% in the current study cohort) which already puts them at an increased risk of atherosclerotic cardiovascular disease. These results may also be useful in public health initiatives for FH cascade screening programs in the UAE and maybe the Gulf region.

2020 ◽  
pp. 204748732090433 ◽  
Author(s):  
Mariann I Lassenius ◽  
Iiro Toppila ◽  
Susanne Bergius ◽  
Julia Perttilä ◽  
KE Juhani Airaksinen ◽  
...  

Aims The study evaluated the quality of cardiovascular prevention in real-world clinical practice. The recurrence of up to five cardiovascular events was assessed, as data on recurrence beyond the first event and interindividual variations in event rates past the second event have been sparse. Low-density lipoprotein cholesterol concentrations and lipid-lowering therapy use were investigated. Methods This retrospective register-based study included adult patients with an incident cardiovascular event between 2004 and 2016 treated in the hospital district of southwest Finland. Patients were followed for consecutive cardiovascular events or cardiovascular death, low-density lipoprotein cholesterol and statin purchases. The timing of event recurrence was evaluated, and predictive factors were assessed. Results A wide interindividual variation in cardiovascular event recurrence was observed, each additional event caused an increased risk, the median time of recurrence decreased from 7 to one year for the second and fifth event. Event rates increased correspondingly from 12 to 43/100 patient-years and were most pronounced in the first years following the previous event. The low-density lipoprotein cholesterol goal (<1.8 mmol/l) was reached by 18% in the year after the event and statin underuse was associated with an increased risk of recurrence. Six months after the index event high intensity statins were used by only 22% of the cohort. Conclusion The study provides new perspectives on individual risk assessment showing that event rates are not stable for all patients but increase 1.2–1.9-fold per consecutive event. The underuse of statins and poor adherence support the identification of these patients for intensified multifactorial preventive measures.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Lee ◽  
S R Lee ◽  
E K Choi ◽  
K D Han ◽  
S Oh

Abstract Background High levels of lipids and lipid variability are established risk factors for atherosclerotic cardiovascular disease. We investigated their roles in the development of atrial fibrillation (AF). This is the largest cohort study yet on the association between lipid levels and AF, and the first study on the association between lipid variability and AF. Methods A nationwide population-based cohort of 3,828,652 adults (mean age 43.9 years) from the Korean National Health Insurance Service database without prevalent AF, not on lipid-lowering medication, and with at least 3 measurements of each lipid parameter at 1–2 year intervals over a 4-year period were included. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were measured, and lipid variability was calculated using variability independent of mean. The cohort was divided into quartiles by baseline lipid levels and lipid variability, and followed up for incident AF. Results During median 3.4 years of follow-up, AF was newly diagnosed in 13,240 (0.35%). AF development was inversely associated with TC and LDL-C levels (for top vs. bottom quartile; TC, hazard ratio [HR] 0.76, 95% confidence interval [95% CI] 0.72–0.80); LDL-C, HR 0.78, 95% CI 0.74–0.82) in both sexes, and with TG levels in men (HR 0.85, 95% CI 0.80–0.90). Meanwhile, AF development was associated with higher LDL-C and HDL-C variability (for top vs. bottom quartile; LDL-C, HR 1.16, 95% CI 1.10–1.22; HDL-C, HR 1.08, 95% CI 1.03–1.14) in both sexes, and with TC variability in men (HR 1.16, 95% CI 1.10–1.22). Conclusions Lower cholesterol levels (TC, LDL-C) and higher cholesterol variability (LDL-C, HDL-C) were associated with higher risk for AF. Low TG levels and high TC variability were also associated with AF incidence in men. These findings support the “cholesterol paradox” in AF, and suggest that cholesterol variability is also a risk factor for AF development.


2019 ◽  
Vol 8 (10) ◽  
pp. 1725 ◽  
Author(s):  
Yinkun Yan ◽  
Lydia A. Bazzano ◽  
Markus Juonala ◽  
Olli T. Raitakari ◽  
Jorma S. A. Viikari ◽  
...  

Background: Data are limited regarding the association of cumulative burden and trajectory of body mass index (BMI) from early life with adult lipid disorders. Methods: The study cohort consisted of 5195 adults who had BMI repeatedly measured 4 to 21 times from childhood and had blood lipid measurements of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) and information on lipid-lowering medications in the last adult survey. The area under the curve (AUC) was calculated as a measure of long-term burden (total AUC) and trends (incremental AUC) of BMI. Results: Participants with dyslipidemia, high LDL-C, low HDL-C and high TG had consistently and significantly higher BMI levels from childhood to adulthood compared to those with normal lipid levels. After adjusting for age, race, sex, and cohort, increased risk of adult dyslipidemia was significantly associated with higher values of childhood BMI, adulthood BMI, total AUC and incremental AUC, with odds ratio (95% confidence interval) = 1.22 (1.15–1.29), 1.85 (1.74–1.97), 1.61 (1.52–1.71), and 1.59 (1.50–1.69), respectively, and p < 0.001 for all. The association patterns were similar in most race–sex subgroups. Conclusions: Adults with dyslipidemia versus normal lipid levels have consistently higher levels and distinct life-course trajectories of BMI, suggesting that the impact of excessive body weight on dyslipidemia originates in early life.


Author(s):  
Sheikh Salahuddin Ahmed

Dyslipidemia is an important risk for the promotion of atherosclerosis and the development of cardiovascular disease (CVD). Currently available drugs can effectively lower the increased levels of blood cholesterol in most patients and prevent the development and progression of CVD. This paper focuses on the adverse cardiovascular effects produced by high blood cholesterols and the overall management of dyslipidemia in adults. Relevant guidelines and research papers published mainly after the year 2000 on the management of dyslipidemia were reviewed. High levels of low density lipoprotein cholesterol (LDL-C), or low levels of high density lipoprotein cholesterol (HDL-C), combined or independently are associated with increased risk of atherosclerotic cardiovascular disease (ASCVD). Apolipoprotein B (ApoB), an atherogenic lipoprotein has emerged recently as the key factor in the pathogenesis of atherosclerosis. High triglyceride (TG) levels are associated with acute and recurrent pancreatitis. The purpose of treating lipid disorders is to prevent the development of ASCVD and pancreatitis. The treatment of dyslipidemia includes multifactorial life style intervention and pharmacotherapy with lipid modifying drugs. Reduction of LDL-C is substantially associated with reduction of risk of ASCVD and evidences show that “lower is better” for LDL-C reduction.


2021 ◽  
Vol 17 ◽  
Author(s):  
Anum Saeed ◽  
Salim S. Virani ◽  
Suresh Mulukutla ◽  
Clara K. Chow

Background: South Asians are at a significantly increased risk of atherosclerotic cardiovascular disease (ASCVD). For a major portion of the South Asian population, the cardiovascular disease events occur at a relatively younger age, are associated with worse outcomes and have potentially more severe socioeconomic implications compared to their western counterparts. Method: The term "South Asian" typically constitutes individuals from India, Pakistan, Nepal, Bhutan, Bangladesh, Sri Lanka, and Maldives and expatriates as well as their families from these countries. Based on this, South Asian form approximately 25% of the world’s population with a high ASCVD burden this group. In this review, we discuss the pathophysiological factors underlying ASCVD in South Asians, the dyslipidemia types and management as well as discuss approaches to improve the overall ASCVD prevention efforts in this large subset population of the world. Although the pathophysiological mechanisms underlying the excess risk of cardiovascular disease in South Asians are multifactorial, dyslipidemia is a primary risk factor for the incidence and prevalence of this disease. The traditional “South Asian” dyslipidemia pattern include levels of low-density lipoprotein cholesterol (LDL-C) in the normal range with high concentration of LDL particles, elevated triglycerides, low levels of high-density lipoprotein cholesterol (HDL-C) with dysfunctional HDL particles, and high levels of lipoprotein(a). Conclusions: While combined efforts to study the expatriate South Asians in western countries have been able to identify South Asian specific dyslipidemias, causal associations and optimal management remains relatively less explored. Larger scale studies are needed to better quantify the relationship of each lipid parameter with ASCVD risk among South Asians as well as optimal lipid targets and management strategies to reduce morbidity and mortality in this high-risk group.


2018 ◽  
Vol 38 (1) ◽  
Author(s):  
Qing-Hui Zhang ◽  
Rui-Xing Yin ◽  
Wu-Xian Chen ◽  
Xiao-Li Cao ◽  
Yu-Ming Chen

Little is known about the association of the TIMD4 (T-cell immunoglobulin and mucin domain 4 gene)-HAVCR1 (hepatitis A virus cellular receptor 1) variants and lipid metabolism, the risk of coronary heart disease (CHD) and ischemic stroke (IS). The present study aimed to determine the TIMD4-HAVCR1 variants, their haplotypes and gene–environment interactions on serum lipid levels, the risk of CHD and IS, and the lipid-lowering efficacy of atorvastatin in a southern Chinese Han population. Genotypes of three variants in 622 controls, 579 CHD, and 546 IS patients were determined by the Snapshot technology. Atorvastatin calcium tablet (20 mg/day) was given in 724 hyperlipidemic patients for 8 weeks after genotyping. The rs12522248 genotypic and allelic frequencies were different between controls and patients, and were associated with the risk of CHD and IS. The rs1501908G-rs12522248T-rs2036402T haplotype was associated with an increased risk of CHD; the G-C-T haplotype was associated with lower risk of CHD; and the C-C-C haplotype was associated with an increased risk of IS. Variants and their haplotypes in controls were associated with triglyceride (rs1501908), low-density lipoprotein cholesterol (LDL-C, rs1501908, G-T-T), high-density lipoprotein cholesterol (HDL-C, rs12522248, C-C-C) and the ratio of total cholesterol (TC) to HDL-C (C-C-C). Interactions of rs1501908- and rs2036402-alcohol (HDL-C); rs1501908- and rs12522248-high body mass index (hBMI, ≥24 kg/m2; TC); and TIMD4-HAVCR1 variants-atorvastatin on several lipid parameters were detected. Interactions of rs12522248TC/CC-hBMI, G-T-T-, and C-C-C-smoking on the risk of CHD; and C-C-C-smoking, C-C-C-, and G-C-T-hBMI on the risk of IS were also observed. These findings suggest that the TIMD4-HAVCR1 variants may be the genetic risk factors for CHD and IS.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yi-Heng Li ◽  
◽  
Wei-Kung Tseng ◽  
Wei-Hsian Yin ◽  
Fang-Ju Lin ◽  
...  

AbstractIn patients with atherosclerotic cardiovascular disease (ASCVD) under statin treatment, the influence of on-treatment level of high-density lipoprotein cholesterol (HDL-C) on cardiovascular (CV) events is controversial. Statin-treated patients were selected from the Taiwanese Secondary Prevention for patients with AtheRosCLErotic disease (T-SPARCLE) Registry, a multicenter, observational study of adult patients with ASCVD in Taiwan. Low HDL-C was defined as < 40 mg/dL for men and < 50 mg/dL for women. The primary outcome was a composite CV events including CV death, myocardial infarction (MI), stroke or cardiac arrest with resuscitation. A total of 3731 patients (mean age 65.6 years, 75.6% men) were included. Patients with on-treatment low HDL-C (44%, mean HDL-C 34.9 ± 6.8 mg/dL) were younger and with more diabetes and higher body weight. The mean follow-up time was 2.7 years. We used restricted cubic spline curves to examine the potential non-linear association between HDL-C and adverse outcomes. Decreased HDL-C levels were associated with a significantly increased risk of CV events in women (< 49 mg/dL in women) but not in men (< 42 mg/dL in men). However, the protective effect of elevated HDL-C levels was more prominent in men than in women. In ASCVD patients with statin therapy, low on-treatment HDL-C was common in Taiwan and associated with an increased risk of CV events in women. Higher HDL-C levels provided more protective effect in men than in women.


Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1504 ◽  
Author(s):  
Cristina Carresi ◽  
Micaela Gliozzi ◽  
Vincenzo Musolino ◽  
Miriam Scicchitano ◽  
Federica Scarano ◽  
...  

Metabolic syndrome (MetS) represents a set of clinical findings that include visceral adiposity, insulin-resistance, high triglycerides (TG), low high-density lipoprotein cholesterol (HDL-C) levels and hypertension, which is linked to an increased risk of developing type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD). The pathogenesis of MetS involves both genetic and acquired factors triggering oxidative stress, cellular dysfunction and systemic inflammation process mainly responsible for the pathophysiological mechanism. In recent years, MetS has gained importance due to the exponential increase in obesity worldwide. However, at present, it remains underdiagnosed and undertreated. The present review will summarize the pathogenesis of MetS and the existing pharmacological therapies currently used and focus attention on the beneficial effects of natural compounds to reduce the risk and progression of MetS. In this regard, emerging evidence suggests a potential protective role of bergamot extracts, in particular bergamot flavonoids, in the management of different features of MetS, due to their pleiotropic anti-oxidative, anti-inflammatory and lipid-lowering effects.


2020 ◽  
Author(s):  
Zhijun Wu ◽  
Zhe Huang ◽  
Alice H. Lichtenstein ◽  
Cheng Jin ◽  
Shuohua Chen ◽  
...  

Abstract Background: Experimental studies found that the functionality of high density lipoprotein cholesterol (HDL-C) may be lost in the presence of diabetes mellitus (DM). We prospectively tested whether DM modified the association between HDL-C concentrations and cardiovascular disease (CVD).Methods: Included were 91,354 Chinese adults (8,244 participants with DM and 83,110 participants without DM) without use of lipid-lowering drugs and free of CVD or cancer at baseline (2006). The primary endpoint of interest was a composite of CVD (myocardial infarction, ischemic stroke and hemorrhagic stroke). Cumulative average HDL-C concentrations were calculated from all available HDL-C measures at baseline (2006) and during the follow-up period (2008, 2010, 2012 and 2014).Results: During a mean of 10.4 year of follow-up, there were 5,076 CVD events identified. Presence of DM significantly modified the association between HDL-C concentrations and CVD risk (Pinteraction =0.003). The association between HDL-C concentrations and CVD followed a U-shaped curve in individuals without DM (Pnonlinearity <0.001). The adjusted hazard ratio (HR) of CVD was 1.25 (95% confidence interval (CI): 1.06-1.48) for HDL-C concentrations <1.04 mmol/L and 1.80 (95% CI: 1.56-2.07) for HDL-C concentrations >2.07 mmol/L, relative to the lowest risk group (HDL-C concentrations of 1.30-1.42mmol/L). In participants with DM, higher HDL-C concentrations were associated with a higher risk of CVD, in a dose-response manner (Pnonlinearity =0.44; Ptrend <0.001). The adjusted HR of CVD was 1.63 (95%CI: 1.20-2.20) for HDL-C concentrations >2.07 mmol/L, relative to HDL-C concentrations of 1.30-1.42mmol/L. Conclusion: High HDL-C concentrations were paradoxically associated with increased risk of composite CVD outcomes in individuals with or without DM. However, low HDL-C concentrations failed to predict future CVD risk in individuals with DM.


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