Journal of atherosclerosis and thrombosis最新文献

{"title":"The Association of the Cholesterol Efflux Capacity with the Paraoxonase 1 Q192R Genotype and the Paraoxonase Activity.","authors":"Kentaro Oniki, Kayoko Ohura, Megumi Endo, Daniel Akatwijuka, Erika Matsumoto, Teruya Nakamura, Yasuhiro Ogata, Minoru Yoshida, Mariko Harada-Shiba, Junji Saruwatari, Masatsune Ogura, Teruko Imai","doi":"10.5551/jat.64711","DOIUrl":"10.5551/jat.64711","url":null,"abstract":"<p><strong>Aims: </strong>Paraoxonase 1 (PON1) binds to high-density lipoprotein (HDL) and protects against atherosclerosis. However, the relationship between functional PON1 Q192R polymorphism, which is associated with the hydrolysis of paraoxon (POXase activity) and atherosclerotic cardiovascular disease (ASCVD), remains controversial. As the effect of PON1 Q192R polymorphism on the HDL function is unclear, we investigated the relationship between this polymorphism and the cholesterol efflux capacity (CEC), one of the biological functions of HDL, in association with the PON1 activity.</p><p><strong>Methods: </strong>The relationship between PON1 Q192R polymorphisms and CEC was investigated retrospectively in 150 subjects without ASCVD (50 with the PON1 Q/Q genotype, 50 with the Q/R genotype, and 50 with the R/R genotype) who participated in a health screening program. The POXase and arylesterase (AREase: hydrolysis of aromatic esters) activities were used as measures of the PON1 activity.</p><p><strong>Results: </strong>The AREase activity was positively correlated with CEC independent of the HDL cholesterol levels. When stratified by the PON1 Q192R genotype, the POXase activity was also positively correlated with CEC independent of HDL cholesterol. PON1 Q192R R/R genotype carriers had a lower CEC than Q/Q or Q/R genotype carriers, despite having a higher POXase activity. Moreover, in a multiple regression analysis, the PON1 Q192R genotype was associated with the degree of CEC, independent of the HDL cholesterol and POXase activity.</p><p><strong>Conclusions: </strong>The PON1 Q192R R allele is associated with reduced CEC in Japanese people without ASCVD. Further studies on the impact of this association on the severity of atherosclerosis and ASCVD development are thus called for.</p>","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11374542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140174777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging the Gap Between the Bench and Bedside: Clinical Applications of High-density Lipoprotein Function.","authors":"Yasuhiro Endo, Kei Sasaki, Katsunori Ikewaki","doi":"10.5551/jat.RV22020","DOIUrl":"10.5551/jat.RV22020","url":null,"abstract":"<p><p>Decades of research have reshaped our understanding of high-density lipoprotein (HDL) , shifting our focus from cholesterol (C) levels to multifaceted functionalities. Epidemiological studies initially suggested an association between HDL-C levels and cardiovascular disease (CVD) risk; however, such a simple association has not been indicated by recent studies. Notably, genome-wide studies have highlighted discrepancies between HDL-C levels and CVD outcomes, urging a deeper exploration of the role of HDL. The key to this shift lies in elucidating the role of HDL in reverse cholesterol transport (RCT), which is a fundamental anti-atherosclerotic mechanism. Understanding RCT has led to the identification of therapeutic targets and novel interventions for atherosclerosis. However, clinical trials have underscored the limitations of HDL-C as a therapeutic target, prompting the re-evaluation of the role of HDL in disease prevention. Further investigations have revealed the involvement of HDL composition in various diseases other than CVD, including chronic kidney disease, Alzheimer's disease, and autoimmune diseases. The anti-inflammatory, antioxidative, and anti-infectious properties of HDL have emerged as crucial aspects of its protective function, opening new avenues for novel biomarkers and therapeutic targets. Omics technologies have provided insights into the diverse composition of HDL, revealing disease-specific alterations in the HDL proteome and lipidome. In addition, combining cell-based and cell-free assays has facilitated the evaluation of the HDL functionality across diverse populations, offering the potential for personalized medicine. Overall, a comprehensive understanding of HDL multifunctionality leads to promising prospects for future clinical applications and therapeutic developments, extending beyond cardiovascular health.</p>","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11374562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141457076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic and Functional Analyses of Patients with Marked Hypo-High-Density Lipoprotein Cholesterolemia.","authors":"Yasuhisa Furuta, Yoshinori Osaki, Yoshimi Nakagawa, Song-Iee Han, Masaya Araki, Akito Shikama, Nami Ohuchi, Daichi Yamazaki, Erika Matsuda, Seitaro Nohara, Yuhei Mizunoe, Kenta Kainoh, Yasuhito Suehara, Hiroshi Ohno, Yoshinori Takeuchi, Takafumi Miyamoto, Yuki Murayama, Yoko Sugano, Hitoshi Iwasaki, Ken-Ichi Hirano, Masahiro Koseki, Shogo Nakano, Hiroaki Tokiwa, Motohiro Sekiya, Naoya Yahagi, Takashi Matsuzaka, Kiyotaka Nakamagoe, Yasushi Tomidokoro, Jun Mitsui, Shoji Tsuji, Hiroaki Suzuki, Hitoshi Shimano","doi":"10.5551/jat.64579","DOIUrl":"10.5551/jat.64579","url":null,"abstract":"<p><strong>Aim: </strong>This study aimed to analyze two cases of marked hypo-high-density lipoprotein (HDL) cholesterolemia to identify mutations in ATP-binding cassette transporter A1 (ABCA1) and elucidate the molecular mechanism by which these novel pathological mutations contribute to hypo-HDL cholesterolemia in Tangier disease.</p><p><strong>Methods: </strong>Wild type and mutant expression plasmids containing a FLAG tag inserted at the C-terminus of the human ABCA1 gene were generated and transfected into HEK293T cells. ABCA1 protein expression and cholesterol efflux were evaluated via Western blotting and efflux assay. The difference in the rate of change in protein expression was evaluated when proteolytic and protein-producing systems were inhibited.</p><p><strong>Results: </strong>In case 1, a 20-year-old woman presented with a chief complaint of gait disturbance. Her HDL-C level was only 6.2 mg/dL. Tangier disease was suspected because of muscle weakness, decreased nerve conduction velocity, and splenomegaly. Whole-exome analysis showed compound heterozygosity for a W484* nonsense mutation and S1343I missense mutation, which confirmed Tangier disease. Cholesterol efflux decreased by a mixture of W484* and S1343I mutations. The S1343I mutation decreased the protein production rate but increased the degradation rate, decreasing the protein levels. This patient also had Krabbe disease. The endogenous ABCA1 protein level of macrophage cell decreased by knocking down its internal galactocerebrosidase. Case 2, a 51-year-old woman who underwent tonsillectomy presented with peripheral neuropathy, corneal opacity, and HDL-C of 3.4 mg/dL. Whole-exome analysis revealed compound heterozygosity for R579* and R1572* nonsense mutations, which confirmed Tangier disease.</p><p><strong>Conclusion: </strong>Case 1 is a new ABCA1 mutation with complex pathogenicity, namely, a W484*/S1343I compound heterozygote with marked hypo-HDL cholesterolemia. Analyses of the compound heterozygous mutations indicated that decreases in ABCA1 protein levels and cholesterol efflux activity caused by the novel S1343I mutation combined with loss of W484* protein activity could lead to marked hypo-HDL cholesterolemia. Galactocerebrosidase dysfunction could also be a potential confounding factor for ABCA1 protein function.</p>","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11374561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140305715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Severity, Outcomes, and their Secular Changes in 33,870 Ischemic Stroke Patients with Atrial Fibrillation in a Hospital-Based Registry: Japan Stroke Data Bank.","authors":"Kazunori Toyoda, Sohei Yoshimura, Michikazu Nakai, Shinichi Wada, Kaori Miwa, Junpei Koge, Takashi Yoshida, Kenji Kamiyama, Tatsuya Mizoue, Taketo Hatano, Yasuhisa Yoshida, Yusuke Sasahara, Akiko Ishigami, Yoshitaka Iwanaga, Yoshihiro Miyamoto, Kazuo Minematsu, Shotai Kobayashi, Masatoshi Koga","doi":"10.5551/jat.65117","DOIUrl":"https://doi.org/10.5551/jat.65117","url":null,"abstract":"<p><strong>Aim: </strong>Severity, functional outcomes, and their secular changes in acute atrial fibrillation (AF)-associated stroke patients were determined.</p><p><strong>Methods: </strong>Acute ischemic stroke patients with AF in a hospital-based, multicenter, prospective registry from January-2000 through December-2020, were compared with those without AF. The co-primary outcomes were the initial severity assessed by the NIH Stroke Scale (NIHSS) score and favorable outcome assessed by the modified Rankin Scale scores 0-2 at hospital discharge.</p><p><strong>Results: </strong>Of the 142,351 patients studied, 33,870 had AF. AF patients had higher NIHSS scores (median 9 vs. 3, adjusted coefficient 5.468, 95% CI 5.354-5.582) than non-AF patients. Favorable outcome was less common in AF patients than in non-AF patients in the unadjusted analysis (48.4% vs. 70.4%), but it was more common with adjustment for the NIHSS score and other factors (adjusted OR 1.110, 95% CI 1.061-1.161). In AF patients, the NIHSS score decreased throughout the 21-year period (adjusted coefficient -0.088, 95% CI -0.115 - -0.061 per year), and the reduction was steeper than in non-AF patients (P＜0.001). In AF patients, favorable outcome became more common over the period (adjusted OR 1.018, 95% CI 1.010-1.026), and the increase was steeper than in non-AF patients (P＜0.001); the increase was no longer significant after further adjustment by reperfusion therapy.</p><p><strong>Conclusions: </strong>Initial stroke severity became milder and functional outcomes improved in AF patients over the 21-year period. These secular changes were steeper than in non-AF patients, suggesting that AF-associated stroke seemed to reap more benefit of recent development of stroke care than stroke without AF.</p>","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142093190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Second Derivative of the Finger Photoplethysmogram Predicts the Risk of Developing Hypertension in Middle-Aged Men.","authors":"Toshiaki Otsuka, Yasuhiro Nishiyama, Katsuhito Kato, Eitaro Kodani, Tomoyuki Kawada","doi":"10.5551/jat.65123","DOIUrl":"https://doi.org/10.5551/jat.65123","url":null,"abstract":"<p><strong>Aim: </strong>Increased arterial stiffness impairs the functional and structural properties of arteries, which in turn elevates blood pressure (BP). The aim of this study was to test whether indices obtained from the second derivative of the finger photoplethysmogram (SDPTG), a marker of arterial stiffness, predict future development of hypertension in middle-aged men.</p><p><strong>Methods: </strong>The SDPTG was measured in 902 men without hypertension (mean age 44±6 years) at an annual medical checkup. The development of hypertension was monitored for a maximum of 4 years. Two indices of arterial stiffness were calculated from the SDPTG waveforms: b/a, an index of large elastic arterial stiffness, and d/a, an index of systemic arterial stiffness, including the structural and functional properties of small and muscular arteries and peripheral circulation. A Cox proportional hazards model was used to examine whether the b/a and d/a ratios were independent predictors of future development of hypertension.</p><p><strong>Results: </strong>During the follow-up period, 124 individuals developed hypertension, defined as a systolic/diastolic BP ≥ 140/90 mm Hg or the use of antihypertensive medications. The hazard ratio for the development of hypertension significantly increased in the lowest quartile of the d/a ratio (2.84, 95% confidence interval: 1.58-5.13, p＜0.001) compared with the highest quartile, after adjusting for multiple potential confounders. In contrast, the b/a ratio did not show significant hazard ratios for the development of hypertension.</p><p><strong>Conclusions: </strong>The d/a ratio, calculated from the SDPTG waveforms, predicted the risk of future development of hypertension in this study population.</p>","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibroblast Growth Factors in Cardiovascular Disease.","authors":"Hideaki Morita, Masaaki Hoshiga","doi":"10.5551/jat.RV22025","DOIUrl":"https://doi.org/10.5551/jat.RV22025","url":null,"abstract":"<p><p>Despite advancements in managing traditional cardiovascular risk factors, many cardiovascular diseases (CVDs) persist. Fibroblast growth factors (FGFs) have emerged as potential diagnostic markers and therapeutic targets for CVDs. FGF1, FGF2, and FGF4 are primarily used for therapeutic angiogenesis. Clinical applications are being explored based on animal studies using approaches such as recombinant protein administration and adenovirus-mediated gene delivery, targeting patients with coronary artery disease and lower extremity arterial disease. Although promising results have been observed in animal models and early-stage clinical trials, further studies are required to assess their therapeutic potential. The FGF19 subfamily, consisting of FGF19, FGF21, and FGF23, act via endocrine signaling in various organs. FGF19, primarily expressed in the small intestine, plays important roles in glucose, lipid, and bile acid metabolism and has therapeutic potential for metabolic disorders. FGF21, found in various tissues, improves glucose metabolism and insulin sensitivity, suggesting potential for treating obesity and diabetes. FGF23, primarily secreted by osteocytes, regulates vitamin D and phosphate metabolism and serves as an important biomarker for chronic kidney disease and CVDs. Thus, FGFs holds promise for both therapeutic and diagnostic applications in metabolic and cardiovascular diseases. Understanding the mechanisms of FGF may pave the way for novel strategies to prevent and manage CVDs, potentially addressing the limitations of current treatments. This review explores the roles of FGF1, FGF2, FGF4, and the FGF19 subfamily in maintaining cardiovascular health. Further research and clinical trials are crucial to fully understand the therapeutic potential of FGFs in managing cardiovascular health.</p>","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treating PAD Patients with Lipoprotein Apheresis.","authors":"Mariko Harada-Shiba","doi":"10.5551/jat.ED269","DOIUrl":"https://doi.org/10.5551/jat.ED269","url":null,"abstract":"","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipid-lowering Therapy and Coronary Plaque Regression.","authors":"Yasushi Ueki, Tadashi Itagaki, Koichiro Kuwahara","doi":"10.5551/jat.RV22024","DOIUrl":"https://doi.org/10.5551/jat.RV22024","url":null,"abstract":"<p><p>Lipid-lowering therapy plays a central role in reducing cardiovascular events. Over the past few decades, clinical trials utilizing several imaging techniques have consistently shown that lipid-lowering therapy can reduce the coronary plaque burden and improve plaque composition. Although intravascular ultrasound has been the most extensively used modality to assess plaque burden, other invasive modalities, such as optical coherence tomography and near-infrared spectroscopy, provide relevant data on plaque vulnerability, and computed tomography angiography detects both plaque volume and characteristics non-invasively. A large body of evidence supports the notion that reducing low-density lipoprotein cholesterol using statins combined with ezetimibe and proprotein convertase subtillisin/kexin type 9 inhibitors consistently shows improvements in plaque burden and favorable morphological changes. This review summarizes previously obtained data on the impact of lipid-lowering treatment strategies on atherosclerotic plaque regression, as assessed using several imaging modalities.</p>","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current Management and Therapy of Severe Aortic Stenosis and Future Perspective.","authors":"Yasuaki Takeji, Hayato Tada, Tomohiko Taniguchi, Kenji Sakata, Takeshi Kitai, Shinichi Shirai, Masayuki Takamura","doi":"10.5551/jat.RV22023","DOIUrl":"https://doi.org/10.5551/jat.RV22023","url":null,"abstract":"<p><p>Intervention for severe aortic stenosis (AS) has dramatically progressed since the introduction of transcatheter aortic valve replacement (TAVR). Decades ago, controversies existed regarding comparing clinical outcomes between TAVR and surgical aortic valve replacement (SAVR) in various risk profiles. Recently, we discussed the durability of transcatheter heart valves and their lifetime management after aortic valve replacement (AVR). Regarding the management of AS, we discuss the appropriate timing of intervention for severe aortic stenosis, especially in asymptomatic patients. In spite of dramatic progression of intervention for AS, there are no established medications available to prevent or slow the progression of AS at present. Basic research and genome studies have suggested several targets associated with the progression of aortic valve calcification. Randomized controlled trials evaluating the efficacy of medications to prevent AS progression are ongoing, which might lead to new strategies for AS management. In this review, we summarize the current management of AS and the drugs expected to prevent the progression of AS.</p>","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Impact of Lipoprotein (a) and Cumulative Low-Density Lipoprotein Cholesterol Exposure on Coronary Artery Disease in Patients with Heterozygous Familial Hypercholesterolemia.","authors":"Daisuke Shishikura, Mariko Harada-Shiba, Masahito Michikura, Shimpei Fujioka, Tomohiro Fujisaka, Hideaki Morita, Yumiko Kanzaki, Masaaki Hoshiga","doi":"10.5551/jat.65009","DOIUrl":"https://doi.org/10.5551/jat.65009","url":null,"abstract":"<p><strong>Aims: </strong>Elevated lipoprotein (a) (Lp[a]), predominantly determined by genetic variability, causes atherosclerotic cardiovascular disease (ASCVD), particularly in patients with familial hypercholesterolemia (FH). We aimed to elucidate the clinical impact of Lp(a) and cumulative exposure to low-density lipoprotein cholesterol (LDL-C) on CAD in patients with FH.</p><p><strong>Methods: </strong>One hundred forty-seven patients clinically diagnosed with heterozygous familial hypercholesterolemia (HeFH) were retrospectively investigated. Patients were divided into 2 groups according to the presence of CAD. Their clinical characteristics and lipid profiles were evaluated.</p><p><strong>Results: </strong>There were no significant differences in untreated LDL-C levels between the 2 groups (p=0.4), whereas the cumulative exposure to LDL-C and Lp(a) concentration were significantly higher in patients with CAD (11956 vs. 8824 mg-year/dL, p＜0.01; 40 vs. 14 mg/dL, p＜0.001, respectively). A receiver operating characteristic (ROC) curve analysis demonstrated that the cutoff values of Lp(a) and cumulative LDL-C exposure to predict CAD in patients with FH were 28 mg/dL (AUC 0.71) and 10600 mg-year/dL (AUC 0.77), respectively. A multivariate analysis revealed that cumulative LDL-C exposure ≥ 10600 mg-year/dL (p＜0.0001) and Lp(a) level ≥ 28 mg/dL (p＜0.001) were independent predictors of CAD. Notably, the risk of CAD remarkably increased to 85.7% with smoking, Lp(a) ≥ 28 mg/dL, and cumulative LDL-C exposure ≥ 10600 mg-year/dL (odds ratio: 46.5, 95%CI: 5.3-411.4, p＜0.001).</p><p><strong>Conclusions: </strong>This study demonstrated an additive effect of Lp(a) and cumulative LDL-C exposure on CAD in patients with HeFH. Interaction with traditional risk factors, particularly smoking and cumulative LDL-C exposure, enormously enhances the cardiovascular risk in this population.</p>","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}