Treatment Of Hypercholesterolemia Research Articles

Global trends and research hotspots of PCSK9 and cardiovascular disease: a bibliometric and visual analysis.

Cardiovascular disease (CVD) is a prevalent non-communicable disease globally and holds the position of being the primary cause of mortality worldwide. Consequently, considerable focus has been directed towards the prevention and management of CVD. PCSK9, a frequently targeted element in the treatment and prevention of CVD, can reduce cardiovascular risk by effectively lowering lipid levels even in the context of statin therapy. It also exhibits substantial potential in the diagnosis and treatment of familial hypercholesterolemia from genetic aspects. This bibliometric study aims to analyze and visualize the global trends and emerging hotspots of PCSK9 and CVD researches and provide researchers with new perspectives in further studies. The data was obtained from the Web of Science Core Collection database. A total of 2,474 publications related to PCSK9 and CVD published between January 2006 and July 2023 were included. The VOSviewer was used to analyze most-cited references, co-authorship, co-citation, co-occurrence and generate a collaborative network map of authors, countries, and institutions. CiteSpace was used to analyze author and institution centroids, keyword bursts, and timeline graphs. A total of 2,474 articles related to CVD and PCSK9 were included. The number of articles and citations show an increasing trend from year to year. Publications were mainly from the United States. The most active institution was Amgen Inc. Watts, Gerald F. was the most prolific author. Atherosclerosis was the most published journal. Literature co-citation and keyword co-occurrence revealed that early studies focused on the lipid-lowering effects of PCSK9 inhibitors in the context of statins therapy, long-term efficacy, adverse effects, LDLR, diagnosis and treatment of familial hypercholesterolemia. In recent years, myocardial ischemic protection, CRISPR-based editing, and new therapeutic strategies for arteriosclerotic cardiovascular disease have gotten wide attention. The protein convertase, inflammation, beta-polyacetate, and inclisiran may be the important future research directions. This study analyses the current status and global trends in the CVD and PCSK9 studies comprehensively, which may provide researchers and policymakers with new and comprehensive perspectives on in this field of research.

Effect of hypercholesterolemia on circulating and cardiomyocyte-derived extracellular vesicles

Hypercholesterolemia (HC) induces, propagates and exacerbates cardiovascular diseases via various mechanisms that are yet not properly understood. Extracellular vesicles (EVs) are involved in the pathomechanism of these diseases. To understand how circulating or cardiac-derived EVs could affect myocardial functions, we analyzed the metabolomic profile of circulating EVs, and we performed an in-depth analysis of cardiomyocyte (CM)-derived EVs in HC. Circulating EVs were isolated with Vezics technology from male Wistar rats fed with high-cholesterol or control chow. AC16 human CMs were treated with Remembrane HC supplement and EVs were isolated from cell culture supernatant. The biophysical properties and the protein composition of CM EVs were analyzed. THP1-ASC-GFP cells were treated with CM EVs, and monocyte activation was measured. HC diet reduced the amount of certain phosphatidylcholines in circulating EVs, independently of their plasma level. HC treatment significantly increased EV secretion of CMs and greatly modified CM EV proteome, enriching several proteins involved in tissue remodeling. Regardless of the treatment, CM EVs did not induce the activation of THP1 monocytes. In conclusion, HC strongly affects the metabolome of circulating EVs and dysregulates CM EVs, which might contribute to HC-induced cardiac derangements.

Causal relationship between depression and hypercholesterolemia: A bidirectional 2-sample Mendelian randomization study.

Although observational studies have found both a positive and negative association between depression and hypercholesterolemia, the findings are mixed and contradictory. To our knowledge, this is the first study that employs the bidirectional Mendelian randomization (MR) and multivariable MR analysis with extensive genome-wide association studies (GWAS) data to examine the causal effect between depression and hypercholesterolemia. Using summary statistics obtained from GWAS of individuals with European ancestry, we utilize a bidirectional 2-sample MR approach to explore the potential causal association between hypercholesterolemia and depressive symptoms. Multivariable Mendelian randomization analysis was used to examine whether the direct causal effect of depression on the risk of hypercholesterolemia can be affected by traits associated with the increased risk of hypercholesterolemia. This MR analysis utilized inverse variance weighted (IVW), MR-Egger regression, weighted mode, and weighted median methods. Data on the summary level of depression were acquired from a GWAS that involved 500,199 participants. We used summary GWAS datasets for hypercholesterolemia including 206,067 participants. We also used another GWAS databases of hypercholesterolemiat (n = 463,010) to validate our results. By utilizing IVW, it was discovered that there is a possibility of a 31% rise in the risk of hypercholesterolemia due to depression (OR = 1.31, 95% CI = 1.10-1.57, P = .002). We found a consistent causal effect of depression on hypercholesterolemia from the IVW analyses using different hypercholesterolemia datasets. After adjustment of smoking, physical activity, and obesity, there remains significant causal relationship between depression and hypercholesterolemia (OR = 1.25, 95% CI = 1.01-1.54, P = .040). However, we did not find any evidence indicating that hypercholesterolemia leads to depression in the opposite direction. Directional pleiotropy was not observed in the MR-Egger regression analysis. Additionally, the MR-PRESSO analysis validated these discoveries. Neither the leave-one-out sensitivity test nor the funnel plots revealed any outliers. In both the unadjusted and adjusted estimates, depression has a consistent direct causal effect on hypercholesterolemia. Our study has led to an improved comprehension of the causal connections between hypercholesterolemia and depression, which could aid in the prevention and treatment of hypercholesterolemia.

Highly variable biological effects of statins on cancer, non-cancer, and stem cells in vitro

Statins, the drugs used for the treatment of hypercholesterolemia, have come into the spotlight not only as chemoadjuvants, but also as potential stem cell modulators in the context of regenerative therapy. In our study, we compared the in vitro effects of all clinically used statins on the viability of human pancreatic cancer (MiaPaCa-2) cells, non-cancerous human embryonic kidney (HEK 293) cells and adipose-derived mesenchymal stem cells (ADMSC). Additionally, the effect of statins on viability of MiaPaCa-2 and ADMSC cells spheroids was tested. Furthermore, we performed a microarray analysis on ADMSCs treated with individual statins (12 μM) and compared the importance of the effects of statins on gene expression between stem cells and pancreatic cancer cells. Concentrations of statins that significantly affected cancer cells viability (< 40 μM) did not affect stem cells viability after 24 h. Moreover, statins that didn´t affect viability of cancer cells grown in a monolayer, induce the disintegration of cancer cell spheroids. The effect of statins on gene expression was significantly less pronounced in stem cells compared to pancreatic cancer cells. In conclusion, the low efficacy of statins on non-tumor and stem cells at concentrations sufficient for cancer cells growth inhibition, support their applicability in chemoadjuvant tumor therapy.

New drugs for the treatment of hyperlipidemia in statin-intolerant patients - review

Introduction Cardiovascular diseases are the most numerous group of diseases prevalent in the world. They are a challenge for many health systems, in terms of keeping life comfortable and also economics. The cause of selected disease entities is too much cholesterol in the blood. The most popular treatment for hypercholesterolemia is based on statins. Many patients are affected by intolerance to these drugs, so an important issue is the discovery and improvement of alternatives to statins. Purpose of work The purpose of this review is to collect literature data on the latest treatments for hypercholesterolemia with drugs other than statins and ezetimibe. Materials and methods Materials are from a review of recent literature available in PubMed. To search for articles, we used keywords such as: bempedoic acid, non-statin therapy, cardiovascular risk, inclisiran, alirocumab, cardiovascular disease, dyslipidemia, evolocumab. Summary Treatment of hypercholesterolemia with statins remains the most popular management strategy. Intolerance to treatment with these drugs creates serious clinical problems for patients. Recently, we could see the emergence of new drugs as alternatives to statins. As the results show, the new drugs can effectively replace statins in the hypolipemic treatment especially of patients who cannot be treated with them.

First report of inclisiran utilization for hypercholesterolemia treatment in real-world clinical settings in a middle east population

First report of inclisiran utilization for hypercholesterolemia treatment in real-world clinical settings in a middle east population

Effect of anti-PCSK9 drugs on the association of PCSK9 to LDL

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protein that is known to interact with the LDL receptor, thereby promoting its degradation and blunting the uptake of LDL from the circulation. In this context, anti-PCSK9 monoclonal antibodies (mAbs) and siRNAs have been approved for the treatment of hypercholesterolaemia. Previous studies have shown that a significant proportion of circulating PCSK9 is associated with LDL. The aim of our research is to investigate the effect of mAbs and siRNA on the association of PCSK9 protein with LDL. In this study, 10 statin-intolerant patients received treatment with anti-PCSK9 mAbs or siRNA, in addition to therapy with a low-dose statin and ezetimibe. Their plasma samples were analysed before and after 1, 3, and 6/9 months of treatment. The results showed that both the monoclonal antibodies and inclisiran reduced LDL-C levels by 50% to 60%. LDL-C levels decreased from 92±28 mg/dL to 44±26 mg/dL after siRNA treatment and reached 97±9, 27±10, 32±14, and 23±10 mg/dL after mAbs therapy. The circulating PCSK9 level decreased by 70% after the first siRNA injection, while it increased 10-fold after mAbs therapy. Regardless of treatment, the percentage of PCSK9 bound to LDL did not vary from baseline and remained constant during the treatment period. Whether this is of physiological relevance remains to be addressed.

A drug repurposing approach of Atorvastatin calcium for its antiproliferative activity for effective treatment of breast cancer: In vitro and in vivo assessment

Breast cancer, the most common cancer among women, caused over 500,000 deaths in 2020. Conventional treatments are expensive and have severe side effects. Drug repurposing is a novel approach aiming to reposition clinically approved non-cancer drugs into newer cancer treatments. Atorvastatin calcium (ATR Ca) which is used for the treatment of hypercholesterolemia has potential to modulate cell growth and apoptosis. The study aimed at utilizing gelucire-based solid lipid nanoparticles (SLNs) and lactoferrin (Lf) as targeting ligand to enhance tumor targeting of atorvastatin calcium for effective management of breast cancer. Lf-decorated-ATR Ca-SLNs showed acceptable particle size and PDI values <200 nm and 0.35 respectively, entrapment efficiency >90% and sustained drug release profile with 78.97 ± 12.3% released after 24 h. In vitro cytotoxicity study on breast cancer cell lines (MCF-7) showed that Lf-decorated-ATR Ca-SLNs obviously improved anti-tumor activity by 2 to 2.5 folds compared to undecorated ATR Ca-SLNs and free drug. Further, In vivo study was also carried out using Ehrlich breast cancer model in mice. Caspase-3 apoptotic marker revealed superior antineoplastic and apoptosis-inducing activity in the groups treated with ATR Ca-SLNs either decorated/ undecorated with Lf in dosage 10 mg/kg/day p < 0.001 with superior activity for lactoferrin-decorated formulation.

Women and familial hypercholesterolemia

Cardiovascular diseases (CVD) are the leading cause of death worldwide. One of the risk factors of CVDs is dyslipidemia, defined as the imbalance of lipids in the blood. Early diagnosis and treatment of the disease is important. However, there appears to be a gender disparity, with women less likely to be diagnosed and start lipid-lowering therapy. In addition, it is difficult for them to continue treatment without interruptions, such as for reasons of childbearing, and as a result they do not achieve the target Low Density Lipoproteins (LDL) levels. Heterozygous Familial Hypercholesterolaemia (FH) is thought to occur in 1 in 500 people in most ethnicities in the world. However, in most cases, these figures are derived from limited numbers of data from selected populations or specific subgroups in the general population and therefore may lack the precision of more modern estimates. About 1 in 200 people have familial hypercholesterolemia, but the vast majority are undiagnosed. Women with untreated FH are at very high risk for early-onset atherosclerotic cardiovascular disease. In untreated women with FH, 30% will develop Atherosclerotic Cardiovascular Disease (ASCVD) by age 60. The onset of ASCVD occurs 20 years earlier in life for women with FH than for women without FH. Regarding women with FH during menopause, they had similar LDL values to premenopausal women and higher levels compared to men in the same age group. Postmenopausal women with FH may suffer the consequences of high LDL either from delayed diagnosis or because of interruptions in management they may have experienced during childbearing. The last 2 decades have seen the development of new therapies to lower LDL-cholesterol levels and delay premature atherosclerosis, especially in combination with lifestyle modifications. Management of patients with familial hypercholesterolemia requires a multiprofessional approach, including primary care providers, cardiologists, endocrinologists, dietitians, pharmacists, and nurses, to improve outcomes. Treatment strategies should be discussed extensively at diagnosis. Close follow-up to monitor treatment response and development of side effects from lipid-lowering agents is essential to optimize care. The representation of women in studies concerning the diagnosis and treatment of familial hypercholesterolemia must be improved, so that there is a more effective treatment of this disease.

Treatment of pediatric heterozygous familial hypercholesterolemia 7 years after the EAS recommendations: Real-world results from a large French cohort

BackgroundHeterozygous familial hypercholesterolemia (HeFH) predisposes to premature cardiovascular diseases. Since 2015, the European Atherosclerosis Society has advocated initiation of statins at 8–10 years of age and a low-density lipoprotein cholesterol (LDL-C) target of <135 mg/dL. Longitudinal data from large databases on pharmacological management of pediatric HeFH are lacking. ObjectiveHere, we describe treatment patterns and LDL-C goal attainment in pediatric HeFH using longitudinal real-world data. MethodsThis was a retrospective and prospective multicenter cohort study (2015–2021) of children with HeFH, diagnosed genetically or clinically, aged <18 years, and followed up in the National French Registry of FH (REFERCHOL). Data on the study population as well as treatment patterns and outcomes are summarized as mean±SD. ResultsWe analyzed the data of 674 HeFH children (age at last visit: 13.1 ± 3.6 years; 82.0 % ≥10 years; 52.5 % females) who were followed up for a mean of 2.8 ± 3.5 years. Initiation of lipid-lowering therapy was on average at 11.8 ± 3.0 years of age for a duration of 2.5 ± 2.8 years. At the last visit, among patients eligible for treatment (573), 36 % were not treated, 57.1 % received statins alone, 6.4 % statins with ezetimibe, and 0.2 % ezetimibe alone. LDL-C was 266±51 mg/dL before treatment and 147±54 mg/dL at the last visit (−44.7 %) in treated patients. Regarding statins, 3.3 %, 65.1 %, and 31.6 % of patients received high-, moderate-, and low-intensity statins, respectively. Overall, 59 % of children on statin therapy alone and 35.1 % on bitherapy did not achieve the LDL-C goal; fewer patients in the older age group did not reach the treatment goal. ConclusionPediatric patients with FH followed up in specialist lipid clinics in France receive late treatment, undertreatment, or suboptimal treatment and half of them do not reach the therapeutic LDL-C goal. Finding a more efficient framework for linking scientific evidence to clinical practice is needed.

Abstract P400: Trajectories of Psychological Well-Being Are Associated With High Cardiovascular Health Late in Life: Findings From the Women’s Health Initiative

Introduction: Psychological well-being (PWB) may influence cardiovascular health (CVH) through what the American Heart Association has called the “mind-heart-body connection”. However, few studies have examined longitudinal relationships between positive PWB and CVH. We estimated associations between trajectories of PWB and Life’s Essential 8 (LE8) achievement. Hypothesis: We hypothesized that women who maintained high levels of PWB over time would have higher LE8 scores later in life. Methods: We conducted group-based trajectory modelling in the Women’s Health Initiative (WHI) to identify latent trajectories of PWB among those with ≥3 measurements of purpose in life (PIL, N=29,717) and personal growth (PG, N=12,148). PIL and PG scores were calculated according to participants’ responses to the FACIT-Sp Meaning Subscale and Ryff’s Scales of PWB, collected between 2000-2021. The selection of trajectory models was informed by statistical criteria and prior literature. Late life CVH (2018-2021) was summarized by LE8, with scoring adapted based on available data: self-reported treatment for hypertension, diabetes, and hypercholesterolemia, and historical food frequency questionnaires were used. Logistic regression was performed to estimate associations between PIL and PG trajectory group membership and high CVH (LE8≥80), summarized by odds ratios (OR) and 95% confidence intervals (CI). Logistic models adjusted for baseline age, WHI study arm, race, marital status, income, and education in those with complete data (PIL N=28,033; PG N=11,495). Results: On average, PIL trajectories spanned 17 years (age 66-83) and three latent groups were identified: high/decreasing (n=12,073; 47.4%), moderate/decreasing (n=12,096; 44.1%), and low/stable (n=2,548; 8.6%). Compared to those in the low/stable group, women in the moderate/decreasing and high/decreasing PIL groups had significantly higher odds of having high CVH (OR 1.47 [1.35, 1.61] and OR 2.09 [1.92, 2.28], respectively). These associations were robust to adjustment for demographics and social determinants of health: moderate/decreasing (aOR 1.40 [1.27, 1.53]), high/decreasing (aOR 1.88 [1.71, 2.07]). PG trajectories spanned 9 years (age 74-83) and high/stable (n=3,832, 31.5%), moderate/stable (n=5,692, 46.9%), and low/stable (n=2,624, 21.6%) latent groups were identified. Membership in moderate/stable (OR 1.53 [1.40, 1.69] and high/stable (OR 1.95 [1.75, 2.16]) PG trajectory groups was also significantly associated with odds of having high CVH. These associations remained significant after adjustment (moderate/stable aOR 1.40 [1.27, 1.55]; high/stable aOR 1.64 [1.46, 1.84]). Conclusions: Maintaining high levels of PIL and PG may contribute to better CVH late in life. Further research is needed to investigate how strategies to improve PWB may be integrated within cardiovascular care among older adults.

Effect of Gracilaria changii extract and its fraction in reverse cholesterol transport by targeting SR-BI gene

This present study aimed to investigate the effects of Gracilaria changii (Red seaweed) extract and its fraction on scavenger receptor class B type I (SR-BI) gene expressions. In vitro studies of the activity of G. changii extract and its fraction against the therapeutic target for hypocholesterolemia were conducted using high-density lipoprotein (HDL) receptor SR-BI via luciferase assay in HepG2 cells. In the current study, methanol crude extract (MCE) and Fraction-2 of G. changii showed the highest expression levels of the SR-BI gene via luciferase assay and increased SR-BI mRNA expression compared to the negative control. Metabolite profiling of the MCE of G. changii by GC-MS revealed nine major compounds, comprising various fatty acids, particularly hexadecenoic acid. Therefore, the MCE and Fraction-2 of G. changii have the potential to be explored in the treatment of hypercholesterolaemia to prevent or reduce the severity of atherosclerosis development.

Familial hypercholesterolaemia: a genetic condition with associated cardiovascular risk

Familial hypercholesterolaemia is a common genetic condition that affects the liver's ability to clear low-density lipoprotein cholesterol from the bloodstream. It affects around one in 250 individuals and is characterised by elevated lipid levels from birth. The causal relationship between raised lipids and cardiovascular disease is well established and the impact of this is evident in familial hypercholesterolaemia. These individuals find themselves at increased risk of premature cardiovascular events as a result of the cumulative lifetime burden of excess cholesterol in the bloodstream. Most individuals with familial hypercholesterolaemia remain undiagnosed and therefore untreated. Early detection and treatment of familial hypercholesterolaemia provides an opportunity to initiate cardiovascular risk prevention, which can reduce the individual's level of risk to that of the general population. Increasing nurses' genetic knowledge and raising awareness of conditions such as familial hypercholesterolaemia can help to improve current rates of detection and provide nurses with the necessary skills to recognise and support patients and their families.

Research Progress in the Clinical Treatment of Familial Hypercholesterolemia.

Familial hypercholesterolemia (FH) is an autosomal dominant inheritable disease with severe disorders of lipid metabolism. It is mainly marked by increasing levels of plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), xanthoma, corneal arch, and early-onset coronary heart disease (CHD). The prevalence of FH is high, and it is dangerous and clinically underdiagnosed. The clinical treatment for FH includes both pharmacological and non-pharmacological treatment, of which non-pharmacological treatment mainly includes therapeutic lifestyle change and dietary therapy, LDL apheresis, liver transplantation and gene therapy. In recent years, many novel drugs have been developed to treat FH more effectively. In addition, the continuous maturity of non-pharmacological treatment techniques has also brought more hope for the treatment of FH. This paper analyzes the pathogenic mechanism and the progress in clinical treatment of FH. Furthermore, it also summarizes the mechanism and structure-activity relationship of FH therapeutic drugs that have been marketed. In a word, this article provides a reference value for the research and development of FH therapeutic drugs.

Impact of statins in the liver: A bane or a boon?

Treatment of hypercholesterolemia with statins is considered one of the cornerstones in the management of atherosclerotic cardiovascular diseases. Statins exert their hypolipidemic effects by inhibiting HMG-CoA reductase, the key enzyme in cholesterol biosynthesis. Beyond cholesterol reduction, statins exhibit pleiotropic effects, including anti-inflammatory, antioxidant, and antiproliferative actions, making them valuable in mitigating atherosclerotic and non-atherosclerotic diseases. Though concerns of hepatotoxicity have been associated with the use of statins, extensive evidence suggests that the risk of statin-induced liver injury (SILI) is rare, with an incidence of &lt;1%. Hepatic adverse effects include reversible asymptomatic transaminase elevation (most frequent), hepatitis, cholestasis, and rarely acute liver failure. While hepatotoxicity concerns should not be dismissed, the evidence overwhelmingly supports the safety of statins. Contrary to the myth of statin hepatotoxicity, real-world data and extensive research emphasize the safety and benefits of statins. They are therapeutic in various liver-related conditions, mainly non-alcoholic fatty liver disease. This scientific review aims to provide a comprehensive overview of statins, shedding light on their mechanism of action, hepatotoxicity concerns, and therapeutic potential in various liver-related conditions.

Early action, lifelong impact: the crucial role of early detection, risk stratification, and aggressive treatment of familial hypercholesterolaemia.

Early action, lifelong impact: the crucial role of early detection, risk stratification, and aggressive treatment of familial hypercholesterolaemia.

PCSK9 vaccines: a promising new strategy for the treatment of hypercholesterolemia?

PCSK9 vaccines: a promising new strategy for the treatment of hypercholesterolemia?

Simultaneous determination of BGT-002 and its acyl glucuronide metabolite ZM326E-M2 in human plasma by liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study

BGT-002, a new type of ATP-citrate lyase inhibitor, is a promising therapeutic for treatment of hypercholesterolemia. After an oral administration of BGT-002 to subjects, it underwent extensive metabolism and an acyl monoglucuronide (ZM326E-M2) on 1- carboxylic acid group was the major circulating metabolite. In this study, an LC-MS/MS method was developed and validated for the simultaneous determination of BGT-002 and ZM326E-M2 in plasma and the evaluation of their pharmacokinetic characteristics in humans. After extraction from the plasma by acetonitrile-induced protein precipitation, the analytes were separated on a Waters ACQUITY UPLC® BEH C18 column using acetonitrile and 2 mM ammonium acetate containing 0.1% formic acid as the mobile phase for gradient elution. Negative electrospray ionization was performed using multiple reaction monitoring (MRM) of m/z 501.3→325.4 for ZM326E-M2 and m/z 507.3→331.2 for D6-ZM326E-M2, and pseudo-MRM of m/z 325.3→325.3 for BGT-002 and m/z 331.3→331.3 for D6-ZM326E, respectively. The method was validated with respect to accuracy, precision, linearity, stability, selectivity, matrix effect, and recovery. The analytical range in human plasma was linear over a concentration range of 0.0500–50.0 μg/mL for BGT-002 and 0.0100–10.0 μg/mL for ZM326E-M2. The pharmacokinetic results showed that after a single oral administration of 100 mg BGT-002, the parent drug was rapidly absorbed with a mean time to peak concentration (tmax) of 1.13 h, compared with BGT-002, the tmax (4.00 h) of ZM326E-M2 was significantly delayed. The peak concentration and plasma exposure of ZM326E-M2 were about 14.1% and 19.5% of the parent drug, suggesting that attention should be paid to the safety and efficacy of ZM326E-M2 in clinical research.

Sex Differences in Diagnosis, Treatment, and Cardiovascular Outcomes in Homozygous Familial Hypercholesterolemia

Homozygous familial hypercholesterolemia (HoFH) is a rare genetic condition characterized by extremely increased low-density lipoprotein (LDL) cholesterol levels and premature atherosclerotic cardiovascular disease (ASCVD). Heterozygous familial hypercholesterolemia (HeFH) is more common than HoFH, and women with HeFH are diagnosed later and undertreated compared to men; it is unknown whether these sex differences also apply to HoFH. To investigate sex differences in age at diagnosis, risk factors, lipid-lowering treatment, and ASCVD morbidity and mortality in patients with HoFH. Sex-specific analyses for this retrospective cohort study were performed using data from the HoFH International Clinical Collaborators (HICC) registry, the largest global dataset of patients with HoFH, spanning 88 institutions across 38 countries. Patients with HoFH who were alive during or after 2010 were eligible for inclusion. Data entry occurred between February 2016 and December 2020. Data were analyzed from June 2022 to June 2023. Comparison between women and men with HoFH regarding age at diagnosis, presence of risk factors, lipid-lowering treatment, prevalence, and onset and incidence of ASCVD morbidity (myocardial infarction [MI], aortic stenosis, and combined ASCVD outcomes) and mortality. Data from 389 women and 362 men with HoFH from 38 countries were included. Women and men had similar age at diagnosis (median [IQR], 13 [6-26] years vs 11 [5-27] years, respectively), untreated LDL cholesterol levels (mean [SD], 579 [203] vs 596 [186] mg/dL, respectively), and cardiovascular risk factor prevalence, except smoking (38 of 266 women [14.3%] vs 59 of 217 men [27.2%], respectively). Prevalence of MI was lower in women (31 of 389 [8.0%]) than men (59 of 362 [16.3%]), but age at first MI was similar (mean [SD], 39 [13] years in women vs 38 [13] years in men). Treated LDL cholesterol levels and lipid-lowering therapy were similar in both sexes, in particular statins (248 of 276 women [89.9%] vs 235 of 258 men [91.1%]) and lipoprotein apheresis (115 of 317 women [36.3%] vs 118 of 304 men [38.8%]). Sixteen years after HoFH diagnosis, women had statistically significant lower cumulative incidence of MI (5.0% in women vs 13.7% in men; subdistribution hazard ratio [SHR], 0.37; 95% CI, 0.21-0.66) and nonsignificantly lower all-cause mortality (3.0% in women vs 4.1% in men; HR, 0.76; 95% CI, 0.40-1.45) and cardiovascular mortality (2.6% in women vs 4.1% in men; SHR, 0.87; 95% CI, 0.44-1.75). In this cohort study of individuals with known HoFH, MI was higher in men compared with women yet age at diagnosis and at first ASCVD event were similar. These findings suggest that early diagnosis and treatment are important in attenuating the excessive cardiovascular risk in both sexes.

Monitoring and treatment of hypercholesterolemia after an atherosclerotic cardiovascular disease event in Denmark from 2015 to 2020

Background and Aims.Lowering the blood concentration of low-density lipoprotein cholesterol (LDL-C), is a cornerstone in preventing atherosclerotic cardiovascular disease (ASCVD). Current European guidelines recommends LDL-C < 1.4 mmol/L for secondary prevention in high-risk patients. The aim of this study is to investigate monitoring and treatment of hypercholesterolemia one year after a ASCVD event. MethodsDanish patients with hypercholesterolemia and an incident ASCVD event from 2015 to 2020 were included in this nationwide cohort study. Patients' LDL-C measurements and lipid-lowering treatment were followed for one year after ASCVD event, or until death or migration. Imputation was used to estimate absolute LDL-values when patients were unmeasured. ResultsA total of 139,043 patients were included in the study with a mean follow-up time of 10.4 months. During the one-year period, 120,020 (86%) patients had their LDL-C measured at least once, 83,723 (60%) patients were measured at least twice. During the period one to six months after ASCVD event 25,999 (19%) achieved an LDL-C < 1.4 mmol/L, 93,349 (67%) failed to achieve an LDL-C < 1.4 mmol/L, and 196,950 (14%) had died or migrated. Missing LDL-C values were estimated via imputation. At the end of month twelve, 60,583 (44%) patients were in statin monotherapy, 2926 (2%) were treated with other lipid-lowering treatment, 42,869 (31%) were in no treatment, and 32,665 (23%) had died or migrated. ConclusionsMany Danish patients are not appropriately followed-up with LDL-C measurements, and a substantial number of patients are not in lipid-lowering treatment one year after an ASCVD event.