Heterozygous Familial Hyperlipidemia in a Fighter Pilot

2021 ◽  
Vol 92 (10) ◽  
pp. 835-837
Author(s):  
Lori C. Gatzke
Keyword(s):  
Coronary Artery ◽  
Early Recognition ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Medical Community ◽  
Atherosclerotic Cardiovascular Disease ◽  
Significant Family History ◽  
Dominant Disease ◽  
Clinically Significant ◽  
Familial Hyperlipidemia

BACKGROUND: Heterozygous familial hypercholesterolemia (HeFH) is an autosomal dominant disease characterized by elevated low-density lipoprotein cholesterol (LDL-C) that increases risk for clinically significant atherosclerotic cardiovascular disease (ASCVD). This common (1:220) disease is present within the fighter pilot community and hesitation to treat this condition at younger ages results in a higher risk for coronary artery disease (CAD), the presence of which can be catastrophic for flying safety. CASE REPORT: A 40-yr-old asymptomatic F-15 pilot presented with persistently elevated LDL-C levels > 190 mg dL1 and a significant family history of CAD. Coronary artery calcium, CT angiography, and finally, invasive angiography were used to further stratify him as having mild CAD. Initiation of statin therapy significantly lowered his LDL and subsequent risk for disease progression, allowing him to return to flying. DISCUSSION: Early recognition and treatment of HeFH is imperative for lowering the risk of ASCVD. Often the medical community supporting flyers is hesitant to diagnose or treat this condition, due to nonrecognition, the young age of presentation, or reluctance to potentially ground a flyer. By intervening earlier, rather than waiting, aviators can remain on flying status longer with lower risk to themselves and their aircrew. Gatzke LC. Heterozygous familial hyperlipidemia in a fighter pilot. Aerosp Med Hum Perform. 2021; 92(10):835837.

Abstract 13422: Long Term Association of Low Density Lipoprotein Patterns With Coronary Artery Calcium and Atherosclerotic Cardiovascular Disease Events: Insights From HeartSCORE Study

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Anum Saeed ◽  
Justin Swanson ◽  
Gul J Saeed ◽  
Kevin Kip ◽  
Steven Reis
Keyword(s):  
Cardiovascular Disease ◽  
Coronary Artery ◽  
Coronary Artery Calcium ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density ◽  
Race And Gender ◽  
And Gender

Introduction: Low-density lipoprotein (LDL) cholesterol, a factor in progression of atherosclerotic cardiovascular disease (CVD), consists of sub-fractions with different sizes and densities in three patterns (A (large buoyant), B (small dense), AB (intermediate pattern). We examined the associations of LDL patterns with subclinical ASCVD and future events. Methods: Participants from the Heart Strategies Concentrating on Risk Evaluation (HeartSCORE) study were assessed for baseline lipid levels and LDL sub-fraction types by an ultracentrifugation method (vertical auto profile). Electron beam CT scans were obtained in a subset of individuals and coronary artery calcium (CAC) scores were calculated (Agatston method). Adjusted odds ratios and hazard ratios (95% CI) were calculated using logistic regression and Cox regression, respectively, to estimate the independent association between LDL sub-fractions and both; CAC and ASCVD events (MI, ischemic stroke, death), respectively. Results: Among 1884 eligible participants (mean [SD] age; 59[7.5]y, 65.8% women, 37.9% black), mean HDL-c, LDL-c and Triglycerides were 142.2[36.0]mg/dL, 58.2[14.9]mg/dL and 111.2[47.7]mmHg, respectively. Sub-fractions of LDL pattern A, B and AB were observed in 761(40%), 507(26.9%) and 616(32.7%) individuals. Over a follow up of ~16y, patterns B(1.98[1.22-3.21) and AB (1.54[1.00-2.38)] were independently associated with incident risk of CVD events (vs pattern A). When stratified by race and gender, pattern AB showed independent risk of incident CVD events and CAC presence among blacks and males (Table) . Conclusions: In this biracial cohort of middle-aged adults, LDL sub-fraction patterns B and AB showed a significantly higher risk of long-term CVD events. Pattern AB was also associated with positive CAC in blacks and males. Further studies are needed to investigate LDL patterns in CVD risk profiling based on race and gender.

Have we learnt all from IMPROVE-IT? Part II. Subanalyses on the ef- fects of ezetimibe added to statin therapy on selected clinical and laborato- ry outcomes, cost effectiveness, guideline and clinical implications

2020 ◽  
Vol 18 ◽  
Author(s):  
Zlatko Fras ◽  
Dimitri P. Mikhailidis
Keyword(s):  
Statin Therapy ◽  
Artery Bypass ◽  
Low Density Lipoprotein ◽  
Bypass Graft ◽  
Density Lipoprotein ◽  
Drug Discontinuation ◽  
Atherosclerotic Cardiovascular Disease ◽  
History Of ◽  
Risk Cost ◽  
Cardiovascular Biomarkers

: In this second part of a review of the IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT), we discuss the findings in relation to patients with stroke, the ACS phenotype, history of coronary artery bypass graft surgery, heart failure, concurrent polyvascular atherosclerotic cardiovascular disease (ASCVD) and diabetes mellitus, and different levels of expression of selected cardiovascular biomarkers. The combination therapy was proven safe, and drug discontinuation rates were not increased by adding ezetimibe. Since both statins and ezetimibe are now almost globally generically available, we can conclude that for secondary prevention of ASCVD, adding ezetimibe to high-intensity statin therapy further reduces low-density lipoprotein cholesterol (LDL-C) and cardiovascular risk cost-effectively.

Clinical implications and outcomes of the ORION Phase III trials

2020 ◽  
Author(s):  
Julia Brandts ◽  
Kausik K Ray
Keyword(s):  
Familial Hypercholesterolemia ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Phase Iii ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density Lipoprotein Cholesterol ◽  
Clinical Safety ◽  
Phase Iii Trials ◽  
Phase Ii And Iii ◽  
Ongoing Phase

Inclisiran is a siRNA inhibiting hepatic PCSK9 synthesis. As a first-in-class therapy, inclisiran has been assessed within the ORION trial program for its low-density lipoprotein cholesterol (LDL-C) lowering efficacy and clinical safety. Phase II and III trials have shown that inclisiran lowers LDL-C by about 50% with an infrequent dosing schedule in patients with established atherosclerotic cardiovascular disease and those at high risk, including patients with heterozygous familial hypercholesterolemia. Ongoing Phase III trials will provide evidence on longer-term safety and effectiveness, and inclisiran’s efficacy in patients with homozygous familial hypercholesterolemia. Furthermore, the ORION-4 trial will assess inclisiran’s impact on cardiovascular outcomes.

scholarly journals Egyptian practical guidance in lipid management 2020

2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Hesham Salah El Din Taha ◽  
Hala Mahfouz Badran ◽  
Hossam Kandil ◽  
Nabil Farag ◽  
Abbas Oraby ◽  
...  
Keyword(s):  
Risk Estimation ◽  
Low Density Lipoprotein ◽  
Management Strategies ◽  
Density Lipoprotein ◽  
Daily Practice ◽  
Main Body ◽  
Atherosclerotic Cardiovascular Disease ◽  
Lipid Management ◽  
Physician Awareness ◽  
User Friendly

Abstract Background Numerous epidemiological investigations and randomized clinical studies have determined that dyslipidemia is a major contributor to atherosclerotic cardiovascular disease (ASCVD). Consequently, the management of serum cholesterol and low-density lipoprotein levels has become a central objective in the effort to prevent cardiovascular events. Main body Many guidelines were issued by different organizations and societies to define patient risk and establish important recommendations for management strategies. Newer cholesterol-lowering agents (non-statin drugs) are described, and their use is directed primarily to secondary prevention in patients at very high risk of new ASCVD. Conclusion The present guidance summarizes the current methods for risk estimation and outlines the most recent data on lipid management in a simple user-friendly format, to improve physician awareness and help implement guidelines in the daily practice.

scholarly journals Impact of Adoption of Directly Measured Low-Density Lipoprotein-Cholesterol (LDL-C) on Targets of Lipid Control and Its Comparison With Friedewald Formula-Calculated LDL Cholesterol in People With Type-2 Diabetes Mellitus

2020 ◽  
pp. 263246362097804
Author(s):  
Rejitha Jagesh ◽  
Mathew John ◽  
Manju Manoharan Nair Jalaja ◽  
Tittu Oommen ◽  
Deepa Gopinath
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Friedewald Formula

Objectives: The accurate and precise measurement of low-density lipoprotein-cholesterol (LDL-C) is important in the assessment of atherosclerotic cardiovascular disease risk (ASCVD) in people with diabetes mellitus. This study aimed at comparing directly measured LDL-C with Friedewald formula (FF)-calculated LDL-C (c-LDL-C) in people with type-2 diabetes. Methods: Fasting lipid profiles of 1905 people with type-2 diabetes, whose LDL-C was estimated by direct LDL assay, were chosen for the study. In the same group, LDL-C was calculated with FF. Correlation and agreement between these methods were analyzed at various strata of triglycerides (TGs). The possibility of misclassifying people at various levels of LDL-C targets proposed in literature was calculated. Results: The mean LDL-C levels were lower in the c-LDL-C group across various TG strata. A significant correlation was found between c-LDL-C and direct LDL-C for all the study samples ( r = 0.948, P < .001) and across all TG strata. Analysis of agreement showed a positive bias for direct LDL-C which increased at higher strata of TGs. c-LDL-C underestimated ASCVD by misclassifying people at various LDL-C target levels. Conclusion: There is a difference between direct LDL-C and c-LDL-C values in people with diabetes and this may result in misclassifying ASCVD especially at lower levels of LDL-C and higher levels of TGs.

scholarly journals Aggregation Susceptibility of Low-Density Lipoproteins—A Novel Modifiable Biomarker of Cardiovascular Risk

2021 ◽  
Vol 10 (8) ◽  
pp. 1769
Author(s):  
Katariina Öörni ◽  
Petri T. Kovanen
Keyword(s):  
Ex Vivo ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density ◽  
Cholesterol Crystals ◽  
Ldl Particles ◽  
Arterial Intima ◽  
Matrix Bound ◽  
Atherosclerotic Cardiovascular Diseases

Circulating low-density lipoprotein (LDL) particles enter the arterial intima where they bind to the extracellular matrix and become modified by lipases, proteases, and oxidizing enzymes and agents. The modified LDL particles aggregate and fuse into larger matrix-bound lipid droplets and, upon generation of unesterified cholesterol, cholesterol crystals are also formed. Uptake of the aggregated/fused particles and cholesterol crystals by macrophages and smooth muscle cells induces their inflammatory activation and conversion into foam cells. In this review, we summarize the causes and consequences of LDL aggregation and describe the development and applications of an assay capable of determining the susceptibility of isolated LDL particles to aggregate when exposed to human recombinant sphingomyelinase enzyme ex vivo. Significant person-to-person differences in the aggregation susceptibility of LDL particles were observed, and such individual differences largely depended on particle lipid composition. The presence of aggregation-prone LDL in the circulation predicted future cardiovascular events in patients with atherosclerotic cardiovascular disease. We also discuss means capable of reducing LDL particles’ aggregation susceptibility that could potentially inhibit LDL aggregation in the arterial wall. Whether reductions in LDL aggregation susceptibility are associated with attenuated atherogenesis and a reduced risk of atherosclerotic cardiovascular diseases remains to be studied.

scholarly journals The LDLR, APOB, and PCSK9 Variants of Index Patients with Familial Hypercholesterolemia in Russia

Genes ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 66
Author(s):  
Alexey Meshkov ◽  
Alexandra Ershova ◽  
Anna Kiseleva ◽  
Evgenia Zotova ◽  
Evgeniia Sotnikova ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Low Density Lipoprotein ◽  
Significant Proportion ◽  
Density Lipoprotein ◽  
Genetic Diagnostics ◽  
Atherosclerotic Cardiovascular Disease ◽  
Gene Variants ◽  
Systematic Analysis ◽  
Pcsk9 Gene ◽  
Cholesterol Levels

Familial hypercholesterolemia (FH) is a common autosomal codominant disorder, characterized by elevated low-density lipoprotein cholesterol levels causing premature atherosclerotic cardiovascular disease. About 2900 variants of LDLR, APOB, and PCSK9 genes potentially associated with FH have been described earlier. Nevertheless, the genetics of FH in a Russian population is poorly understood. The aim of this study is to present data on the spectrum of LDLR, APOB, and PCSK9 gene variants in a cohort of 595 index Russian patients with FH, as well as an additional systematic analysis of the literature for the period of 1995–2020 on LDLR, APOB and PCSK9 gene variants described in Russian patients with FH. We used targeted and whole genome sequencing to search for variants. Accordingly, when combining our novel data and the data of a systematic literature review, we described 224 variants: 187 variants in LDLR, 14 variants in APOB, and 23 variants in PCSK9. A significant proportion of variants, 81 of 224 (36.1%), were not described earlier in FH patients in other populations and may be specific for Russia. Thus, this study significantly supplements knowledge about the spectrum of variants causing FH in Russia and may contribute to a wider implementation of genetic diagnostics in FH patients in Russia.

Low-density lipoprotein cholesterol goal attainment and treatment patterns in a cohort of >143,000 patients with atherosclerotic cardiovascular disease in Ontario, Canada

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Fairbairn ◽  
P Oh ◽  
R Goeree ◽  
R.M Rogoza ◽  
M Packalen ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Goal Attainment ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Data Repository ◽  
Funding Source ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol

Abstract Background/Introduction Limited real-world data are available on attainment of low-density lipoprotein cholesterol (LDL-C) treatment goals in patients with atherosclerotic cardiovascular disease (ASCVD) in Canada. Purpose A retrospective observational study was conducted to describe types of ASCVD events/procedures, time between events and use of lipid lowering treatment (LLT) in patients who did not achieve LDL-C goal. Methods Patients in Ontario ≥65 years with a primary ASCVD event/procedure between 1 Apr 2005 and 31 Mar 2016, treated with an LLT and with index and follow up LDL-C values were identified from claims data at the Institute for Clinical Evaluative Sciences data repository. Patients were assessed over a 1-year follow up period for LDL-C goal attainment (&lt;2.0 mmol/L or 50% reduction from index LDL-C) and analysed by LLT and by index event type. Results Overall, 28% of 143,302 patients ≥65 years on LLT failed to attain LDL-C goal at follow up (Figure). The proportion of patients failing to achieve LDL-C goal decreased from 35% to 22% over the 11-year study period. Mean time between index and follow up LDL-C (based on lowest score &gt;2 weeks and up to 1 year after index LDL-C) was 203±97 days. When analysed by low-, moderate- or high-intensity statin, 57%, 30%, and 22% of patients failed to achieve LDL-C goal at follow up, respectively. Conclusions In this study, more than 1 in 4 patients with ASCVD in Ontario failed to achieve guideline recommended LDL-C goal despite treatment. In particular, ∼1 in 3 patients with cerebral and peripheral arterial disease were not at goal. An opportunity exists to better manage these high risk ASCVD patients with further statin intensification and additional LLTs This study made use of de-identified data from the ICES Data Repository, which is managed by the Institute for Clinical Evaluative Sciences with support from its funders and partners: Canada's Strategy for Patient-Oriented Research (SPOR), the Ontario SPOR Support Unit, the Canadian Institutes of Health Research and the Government of Ontario. The opinions, results and conclusions reported are those of the authors. No endorsement by ICES or any of its funders or partners is intended or should be inferred. Parts of this material are based on data and/or information compiled and provided by CIHI. However, the analyses, conclusions, opinions and statements expressed in the material are those of the author(s), and not necessarily those of CIHI Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Amgen Canada Inc.

scholarly journals Platelet CD36 signaling through ERK5 promotes caspase-dependent procoagulant activity and fibrin deposition in vivo

2018 ◽  
Vol 2 (21) ◽  
pp. 2848-2861 ◽  
Author(s):  
Moua Yang ◽  
Andaleb Kholmukhamedov ◽  
Marie L. Schulte ◽  
Brian C. Cooley ◽  
Na’il O. Scoggins ◽  
...  
Keyword(s):  
Platelet Reactivity ◽  
Low Density Lipoprotein ◽  
Scavenger Receptor ◽  
Density Lipoprotein ◽  
Signaling Molecules ◽  
Chow Diet ◽  
Glycoprotein Vi ◽  
Platelet Signaling ◽  
Clinically Significant

Abstract Dyslipidemia is a risk factor for clinically significant thrombotic events. In this condition, scavenger receptor CD36 potentiates platelet reactivity through recognition of circulating oxidized lipids. CD36 promotes thrombosis by activating redox-sensitive signaling molecules, such as the MAPK extracellular signal-regulated kinase 5 (ERK5). However, the events downstream of platelet ERK5 are not clear. In this study, we report that oxidized low-density lipoprotein (oxLDL) promotes exposure of procoagulant phosphatidylserine (PSer) on platelet surfaces. Studies using pharmacologic inhibitors indicate that oxLDL-CD36 interaction–induced PSer exposure requires apoptotic caspases in addition to the downstream CD36-signaling molecules Src kinases, hydrogen peroxide, and ERK5. Caspases promote PSer exposure and, subsequently, recruitment of the prothrombinase complex, resulting in the generation of fibrin from the activation of thrombin. Caspase activity was observed when platelets were stimulated with oxLDL. This was prevented by inhibiting CD36 and ERK5. Furthermore, oxLDL potentiates convulxin/glycoprotein VI–mediated fibrin formation by platelets, which was prevented when CD36, ERK5, and caspases were inhibited. Using 2 in vivo arterial thrombosis models in apoE-null hyperlipidemic mice demonstrated enhanced arterial fibrin accumulation upon vessel injury. Importantly, absence of ERK5 in platelets or mice lacking CD36 displayed decreased fibrin accumulation in high-fat diet–fed conditions comparable to that seen in chow diet–fed animals. These findings suggest that platelet signaling through CD36 and ERK5 induces a procoagulant phenotype in the hyperlipidemic environment by enhancing caspase-mediated PSer exposure.

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