Journal of clinical lipidology最新文献

{"title":"The joint association of lipoprotein(a) and lipoprotein-associated phopholipase A2 with the risk of stroke recurrence","authors":"Jing Xue MD, PhD ,&nbsp;Yukun Xiang MD ,&nbsp;Xue Jiang PhD ,&nbsp;Aoming Jin PhD ,&nbsp;Xiwa Hao MD, PhD ,&nbsp;Ke Li MD ,&nbsp;Jinxi Lin PhD ,&nbsp;Xia Meng MD, PhD ,&nbsp;Hao Li PhD ,&nbsp;Lemin Zheng PhD ,&nbsp;Yongjun Wang MD, PhD ,&nbsp;Jie Xu MD, PhD","doi":"10.1016/j.jacl.2024.04.133","DOIUrl":"10.1016/j.jacl.2024.04.133","url":null,"abstract":"<div><h3>BACKGROUND AND PURPOSE</h3><div>Currently little is known about the joint association of lipoprotein (a) [Lp(a)] and lipoprotein-associated phospholipase A2 (Lp-PLA2) with stroke recurrence.</div></div><div><h3>METHODS</h3><div>In this prospective multicenter cohort study, 10,675 consecutive acute ischemic stroke (IS) and transient ischemic attack (TIA) patients with Lp(a) and Lp-PLA2 were enrolled. The association of stroke recurrence within 1 year with Lp(a) and Lp-PLA2 was assessed using Cox proportional hazards models and Kaplan-Meier curves. The interaction between Lp(a) and Lp-PLA2 with stroke recurrence was evaluated by multiplicative and additive scales.</div></div><div><h3>RESULTS</h3><div>A significant joint association of Lp(a) and Lp-PLA2 with the risk of stroke recurrence was observed. Multivariate Cox regression analysis demonstrated that the combination of elevated Lp(a) (≥ 50 mg/dL) and Lp-PLA2 (≥175.1 ng/mL) was independently associated with the risk of stroke recurrence (adjusted hazard ratio: 1.42; 95% confidence interval [CI]: 1.15–1.76). Both significant multiplicative [(exp(β3): 1.63, 95% CI: 1.17–2.29, <em>P</em> = 0.004] and additive interaction (RERI: 0.55, 95% CI: 0.20–0.90, <em>P</em> = 0.002; AP: 0.39, 95% CI, 0.24–0.53) were observed between Lp(a) and Lp-PLA2.</div></div><div><h3>CONCLUSIONS</h3><div>Our results indicated that Lp(a) and Lp-PLA2 have a joint association with the risk of stroke recurrence in IS/TIA patients. Patients with concomitant presence of elevated Lp(a) and Lp-PLA2 have greater risk of stroke recurrence.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"18 5","pages":"Pages e729-e737"},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141025059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world experience of long-term efficacy and safety of evinacumab in patients with homozygous familial hypercholesterolemia treated and untreated with lipoprotein apheresis","authors":"Claudia Stefanutti MD, PhD ,&nbsp;Dick C. Chan PhD ,&nbsp;Giovanna Zeppa Dip ,&nbsp;Gerald F. Watts DSc, PhD, DM","doi":"10.1016/j.jacl.2024.05.006","DOIUrl":"10.1016/j.jacl.2024.05.006","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>Evinacumab is an inhibitor of angiopoietin-like 3 protein (ANGPTL3) that offers a new approach for correcting high low-density lipoprotein-cholesterol (LDL-C) and may reduce the need or frequency for lipoprotein apheresis (LA) in patients with homozygous familial hypercholesterolemia (HoFH).</div></div><div><h3>OBJECTIVE</h3><div>We aimed to investigate the long-term efficacy and safety of evinacumab in patients with HoFH aged between 14 and 63 years on and off LA in real-world clinical practice.</div></div><div><h3>METHODS</h3><div>Evinacumab was administrated intravenously (15 mg /kg every 4 weeks) for the first 24 months in 7 patients with genetically confirmed HoFH, receiving best standard of lipid-lowering treatment and LA, followed by a subsequent compassionate extension period of approximately 12-month treatment with evinacumab without LA. Patient experience of evinacumab and health-related EuroQol (EQ-5D-3L) quality of life questionnaire were also assessed.</div></div><div><h3>RESULTS</h3><div>Compared with baseline, evinacumab resulted in sustained reductions in plasma LDL-C concentration of -43.4% and -54.2% at 30 and 36 months, respectively. All 7 HoFH patients achieved an LDL-C reduction &gt;30% with 3 patients having on-treatment LDL-C level &lt; 2.5 mmol/L (96 mg/dL). Evinacumab was well-tolerated, with no major adverse events reported or significant changes in liver enzyme concentrations. All FH patients agreed that evinacumab was acceptable and less physically demanding than LA. The mean EQ- utility score and visual analogue score were 0.966 and 78.6, respectively, which are comparable to the Italian general population.</div></div><div><h3>CONCLUSIONS</h3><div>Our findings suggest that evinacumab is a safe and effective treatment for high LDL-C that is acceptable to HoFH patients receiving and not receiving LA.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"18 5","pages":"Pages e817-e824"},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141531464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of physical examinations of tendon xanthomas and changes in the cutoff values of Achilles tendon thickness on radiography in the clinical criteria of heterozygous familial hypercholesterolemia in Japan","authors":"Hayato Tada MD ,&nbsp;Atsushi Nohara MD ,&nbsp;Soichiro Usui MD ,&nbsp;Kenji Sakata MD ,&nbsp;Masa-aki Kawashiri MD ,&nbsp;Masayuki Takamura MD","doi":"10.1016/j.jacl.2024.06.008","DOIUrl":"10.1016/j.jacl.2024.06.008","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>The 2022 Japan Atherosclerosis Society familial hypercholesterolemia (FH) clinical criteria were modified. In particular, the cutoff value of Achilles tendon thickness (ATT) on radiography was changed from ≥9 mm in both sexes to ≥8.0 mm in men and ≥7.5 mm in women.</div></div><div><h3>METHODS</h3><div>A total of 872 patients with FH were retrospectively reviewed. Patients were categorized by an ATT of &lt;7.5/8.0 mm (group 1), ≥7.5/8.0 and &lt;9.0 mm (group 2, new group with FH by ATT), and ≥9 mm (group 3).</div></div><div><h3>RESULTS</h3><div>In total, 492 patients fell into group 1, 102 in group 2, and 263 in group 3, and 14.0%, 55.9%, and 79.8% of patients in groups 1, 2, and 3, respectively, were positive for a FH mutation. Further, among patients with low-density lipoprotein cholesterol &gt;180 mg/dL, 37.3%, 77.3%, and 86.5% of patients had a FH mutation in groups 1, 2, and 3, respectively. The proportion of patients with protein-truncating mutation (3.8%, 16.7%, and 53.2%, respectively) differed significantly across groups 1 through 3, respectively. Interestingly, only a very small proportion of the patients in groups 2 and 3 had palpable xanthomas (3.0% and 14.4% respectively).</div></div><div><h3>CONCLUSIONS</h3><div>This study validates the new radiographic ATT criteria, since the vast majority of patients in the intermediate ATT category had true FH, as shown by positive genetic testing, whereas the old ATT criteria left them with just a deferred diagnosis of FH. In addition, use of physical examination alone for the presence of tendon xanthoma may lead to underdiagnosis of FH.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"18 5","pages":"Pages e825-e831"},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141611981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 with inclisiran in the real-world setting: Initial data from a national health care service","authors":"Ibrahim Naoum MD ,&nbsp;Walid Saliba MD, MPH ,&nbsp;Amir Aker MD ,&nbsp;Barak Zafrir MD","doi":"10.1016/j.jacl.2024.05.003","DOIUrl":"10.1016/j.jacl.2024.05.003","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>Inclisiran, a small-interfering RNA enabling long-term inhibition of proprotein convertase subtilisin kexin type 9 (PCSK9) synthesis, demonstrates a good safety and efficacy profile in clinical trials. Real-world data on the potential to attain lipid-goals and reduce treatment gaps are lacking.</div></div><div><h3>OBJECTIVES</h3><div>To investigate the implementation of inclisiran in real-world clinical setting.</div></div><div><h3>METHODS</h3><div>Data from a nationwide healthcare organization on patients initiating inclisiran between 3/2022–11/2023. Patients’ characteristics, lipid-lowering therapies, post-treatment reduction in low-density lipoprotein cholesterol (LDL-C), and attainment of treatment goals were evaluated.</div></div><div><h3>RESULTS</h3><div>Inclisiran was initiated by 503 patients (57% women; mean age 66±11 years). Cardiovascular disease was present in 54%, and peak LDL-C levels &gt;190 mg/dL documented in 64%. Prior exposure to PCSK9 monoclonal antibodies was evident in 28%. Lipid profile &gt;2 months after filling first prescription, was available in 397 patients (347 with ≥2 injections). In patients treated by inclisiran only (<em>n</em> = 254), median LDL-C reduction from peak levels was 57% (interquartile range [IQR], 48%-67%), and from pre-injection levels 40% (19%-54%). In those with concomitant lipid-lowering therapies (<em>n</em> = 143), median LDL-C reduction from peak levels was 66% (IQR, 55%-73%), and from pre-injection levels 46% (23%-59%). LDL-C &lt; 70 mg/dL was attained by 39% and LDL-C &lt; 55 mg/dL by 21.9%. Of those treated with concomitant statin therapy, 38% attained LDL-C &lt; 55 mg/dL. Overall, 6.5% discontinued inclisiran therapy after initial injection.</div></div><div><h3>CONCLUSIONS</h3><div>In real-world practice, inclisiran showed good efficacy in reducing LDL-C with high interindividual variability. However, attainment rates of lipid goals were suboptimal due to limited use of combination lipid-lowering therapy and high rates of severe hypercholesterolemia in our patient population cohort.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"18 5","pages":"Pages e809-e816"},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141144503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of residual inflammatory risk and LDL cholesterol in patients with in-stent restenosis undergoing percutaneous coronary intervention","authors":"Han Zhang MD ,&nbsp;Chujie Zhang ,&nbsp;Yin Zhang MB ,&nbsp;Tao Tian MD ,&nbsp;Tianjie Wang MD ,&nbsp;Jue Chen MD ,&nbsp;Jie Qian MD ,&nbsp;Fenghuan Hu MD ,&nbsp;Kefei Dou MD ,&nbsp;Shubin Qiao MD ,&nbsp;Yongjian Wu MD ,&nbsp;Changdong Guan MSc ,&nbsp;Weixian Yang MD ,&nbsp;Lei Song MD","doi":"10.1016/j.jacl.2024.05.009","DOIUrl":"10.1016/j.jacl.2024.05.009","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>To evaluate the relationships between residual inflammatory risk [assessed by high-sensitivity C-reactive protein (hsCRP)], residual cholesterol risk [assessed by low-density lipoprotein cholesterol (LDL-C)] and clinical outcomes among patients who underwent percutaneous coronary intervention (PCI) for in-stent restenosis (ISR) lesions.</div></div><div><h3>METHODS</h3><div>Between January 2017 and December 2018, a total of 2079 patients who underwent PCI for ISR were consecutively enrolled. The primary outcome was the rate of major adverse cardiac events (MACE), defined as a composite endpoint of all-cause death, spontaneous myocardial infarction (MI), or repeat revascularization.</div></div><div><h3>RESULTS</h3><div>During a median follow-up of 36 months, 436 MACEs occurred. Baseline hsCRP was significantly associated with MACE (highest versus lowest quartile, adjusted hazard ratio [aHR] 1.90 [95% CI, 1.39–2.59]; <em>P</em> &lt; 0.001). By contrast, the baseline LDL-C quartile was not associated with MACE (highest versus lowest quartile, aHR 0.93 [95% CI, 0.71- 1.22]; <em>P</em> = 0.59). Compared with patients without residual risk (hsCRP &lt;2 mg/L and LDL-C &lt; 70 mg/dL), participants with both residual inflammatory and LDL-C risk (hsCRP ≥2 mg/L and LDL-C ≥ 70 mg/dL) (aHR, 1.39 [95% CI, 1.06–1.83]; <em>P</em> = 0.02) and those with residual inflammatory risk only (hsCRP ≥2 mg/L and LDL-C &lt; 70 mg/dL) (aHR, 1.34 [95% CI, 1.01–1.72]; <em>P</em> = 0.04) had significantly higher risks of MACE.</div></div><div><h3>CONCLUSIONS</h3><div>In the current cohort of patients after ISR PCI, inflammation assessed by hsCRP predicted higher risk of adverse clinical outcomes, whereas the level of LDL-C was not associated with adverse prognosis.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"18 5","pages":"Pages e746-e755"},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141400091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of evolocumab on carotid plaque composition in asymptomatic carotid artery stenosis (EVOCAR-1) using magnetic resonance imaging","authors":"Ben Jones PhD ,&nbsp;Neil Rane FRCR ,&nbsp;Mary Finnegan PhD ,&nbsp;Rebecca Quest PhD ,&nbsp;Mariana Abdel-Malek MRCP ,&nbsp;Luca Biasiolli PhD ,&nbsp;Joseph Shalhoub PhD ,&nbsp;Alun Davies FRCS ,&nbsp;Naomi Loyse PhD ,&nbsp;Paul Bassett MSc ,&nbsp;Kausik K Ray FMedSci ,&nbsp;Jaimini Cegla PhD","doi":"10.1016/j.jacl.2024.06.004","DOIUrl":"10.1016/j.jacl.2024.06.004","url":null,"abstract":"<div><h3>Background and Aims</h3><div>To determine the effect of evolocumab treatment in patients with asymptomatic carotid artery stenosis ≥50% on carotid plaque morphology and composition, as determined by magnetic resonance imaging.</div></div><div><h3>Methods</h3><div>We conducted a double-blind randomized controlled trial in patients with asymptomatic carotid artery plaque with ≥50% stenosis and low-density lipoprotein-associated cholesterol (LDL-C) ≥1.8 mmol/L, despite standard lipid-lowering therapy, with 12 months of evolocumab or placebo injection every two weeks. The primary endpoint was the between group difference in the absolute change from baseline in carotid plaque lipid-rich necrotic core (LRNC), assessed by carotid magnetic resonance.</div></div><div><h3>Results</h3><div>Due to interrupted recruitment during the COVID-19 pandemic, 33 patients (36% female) were randomised, which was less than the target of 52. Mean age was 68.7 years (SD, 8.5) and baseline LDL-C 2.4 mmol/L (SD, 0.7). LDL-C was reduced with evolocumab to 0.8 mmol/L (SD, 0.5) vs 2.2 mmol/L (SD, 0.7) with placebo at 3 months (between group absolute difference -1.3 mmol/L [95% confidence interval [CI], -1.7 to -0.9], <em>p</em> &lt; 0.001). Evolocumab treatment was associated with a favourable change in LRNC at 12 months of -16 mm³ (SD, 54) whereas the placebo group showed -4 mm³ (SD, 44). Between group differences did not show statistical significance with a placebo-adjusted LRNC change of -17 mm³ ([95% CI, -45 to 12], <em>p</em> = 0.25). Percentage carotid plaque LRNC also numerically reduced at 12 months, however this did not reach statistical significance (-2.4% vessel wall volume [95% CI, -5.7 to 0.9], <em>p</em> = 0.16).</div></div><div><h3>Conclusion</h3><div>Intensive LDL-C lowering with the addition of evolocumab to maximally tolerated lipid-lowering therapy did not lead to a statistically significant change in vulnerable plaque phenotype characteristics in patients with asymptomatic carotid artery stenosis, but the study was underpowered due to under-recruitment in the context of the COVID-19 pandemic.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"18 5","pages":"Pages e855-e866"},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141404685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Usefulness of triglyceride-glucose index and homeostatic model assessment for predicting coronary microvascular dysfunction","authors":"Mustafa Bulut MD ,&nbsp;Fatma Betul Celik MD ,&nbsp;Tolga Sinan Guvenc MD ,&nbsp;Yusuf Yilmaz MD ,&nbsp;Mehmet Celik MD ,&nbsp;Serhan Ozyildirim MD ,&nbsp;Kemal Gocer MD ,&nbsp;Murat Asik MD ,&nbsp;Seref Kul MD ,&nbsp;Mustafa Caliskan MD","doi":"10.1016/j.jacl.2024.04.135","DOIUrl":"10.1016/j.jacl.2024.04.135","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>Coronary microvascular dysfunction (CMD) is a common occurrence in individuals with insulin resistance (IR). Homeostatic model assessment for insulin resistance (HOMA-IR) is a widely used surrogate marker of IR, although recent studies suggest triglyceride-glucose (TyG) index is a superior marker of IR that had a better accuracy to predict type 2 diabetes or cardiovascular outcomes than HOMA-IR.</div></div><div><h3>OBJECTIVES</h3><div>We aimed to assess the accuracy and usefulness of TyG index and HOMA-IR for predicting CMD as assessed with echocardiographic coronary flow reserve (CFR) measurement.</div></div><div><h3>METHODS</h3><div>All cases included in the institutional CFR registry were retrospectively reviewed, and 656 cases without epicardial coronary artery disease and without major risk factors for atherosclerosis were included. A CFR ≤2.0 was defined as CMD.</div></div><div><h3>RESULTS</h3><div>TyG index was available in all cases, while HOMA-IR was available in 398 cases. Both TyG index and HOMA-IR were associated with CMD on univariate analyses, while after adjustment for potential confounders HOMA-IR (odds ratio [OR]:1.38, 95% confidence interval [CI]:1.14–1.67, <em>p</em> = 0.001) but not TyG index (OR:1.48, 95% CI:0.82–2.67, <em>p</em> = 0.19) was associated with CMD. The predictive accuracy of HOMA-IR (c-statistic:0.63, 95% CI:0.54–0.72, <em>p</em> = 0.003) was higher than TyG index(c-statistic:0.55, 95% CI:0.47–0.63, <em>p</em> = 0.13), although the difference was not statistically significant (DeLong <em>p</em> = 0.23). There was strong evidence favoring a true difference between CMD vs. non-CMD groups for HOMA-IR (BF₁₀:3507) but not for TyG index(BF₁₀:0.66).</div></div><div><h3>CONCLUSIONS</h3><div>HOMA-IR, but not TyG index, is closely associated with CMD.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"18 5","pages":"Pages e764-e772"},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141045154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of lipid-lowering drugs with gut microbiota: A Mendelian randomization study","authors":"Lubo Shi MM ,&nbsp;Xiaoduo Liu MM ,&nbsp;Enze Li MM ,&nbsp;Shutian Zhang MD ,&nbsp;Anni Zhou MD","doi":"10.1016/j.jacl.2024.05.004","DOIUrl":"10.1016/j.jacl.2024.05.004","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>The gut microbiota can be influenced by lipid metabolism. We aimed to evaluate the impact of lipid-lowering medications, such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, Niemann-Pick C1-Like 1 protein (NPC1L1) inhibitors, and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) inhibitors, on gut microbiota through drug target Mendelian randomization (MR) investigation.</div></div><div><h3>METHODS</h3><div>We used genetic variants that were associated with low-density lipoprotein cholesterol (LDL-C) in genome-wide association studies and located within or near drug target genes as proxies for lipid-lowering drug exposure. In addition, expression trait loci in drug target genes were used as complementary genetic tools. We used effect estimates calculated using inverse variance weighted MR (IVW-MR) and summary data-based MR (SMR). Multiple sensitivity analyses were performed.</div></div><div><h3>RESULTS</h3><div>Genetic proxies for lipid-lowering drugs broadly affected the abundance of gut microbiota. High expression of NPC1L1 was significantly associated with an increase in the genus Eggerthella (β = 1.357, SE = 0.337, <em>P</em> = 5.615 × 10⁻⁵). An HMGCR-mediated increase in LDL-C was significantly associated with the order Pasteurellales (β = 0.489, SE = 0.123, <em>P</em> = 6.955 × 10⁻⁵) and the genus Haemophilus (β = 0.491, SE = 0.125, <em>P</em> = 8.379 × 10⁻⁵), whereas a PCSK9-mediated increase in LDL-C was associated with the genus Terrisporobacter (β = 0.666, SE = 0.127, <em>P</em> = 1.649 × 10⁻⁵). No pleiotropy was detected.</div></div><div><h3>CONCLUSIONS</h3><div>This drug target MR highlighted the potential interventional effects of lipid-lowering drugs on the gut microbiota and separately revealed the possible effects of different types of lipid-lowering drugs on specific gut microbiota.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"18 5","pages":"Pages e797-e808"},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141414986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum mature and furin-cleaved proprotein convertase subtilisin/kexin type 9 levels and their association with cardiovascular events in statin-treated patients with cardiovascular disease","authors":"Kiyoshi Hibi MD, PhD ,&nbsp;Masaomi Gohbara MD, PhD ,&nbsp;Kohei Uemura MSc, PhD ,&nbsp;Noriaki Iwahashi MD, PhD ,&nbsp;Kozo Okada MD, PhD ,&nbsp;Hiroshi Iwata MD, PhD ,&nbsp;Yoshihiro Fukumoto MD, PhD ,&nbsp;Takafumi Hiro MD, PhD ,&nbsp;Yukio Ozaki MD, PhD ,&nbsp;Satoshi Iimuro MD, PhD ,&nbsp;Ichiro Sakuma MD, PhD ,&nbsp;Seiji Hokimoto MD, PhD ,&nbsp;Katsumi Miyauchi MD, PhD ,&nbsp;Yutaka Matsuyama PhD ,&nbsp;Yoshihisa Nakagawa MD, PhD ,&nbsp;Hisao Ogawa MD, PhD ,&nbsp;Hiroyuki Daida MD, PhD ,&nbsp;Hiroaki Shimokawa MD, PhD ,&nbsp;Yasushi Saito MD, PhD ,&nbsp;Takeshi Kimura MD, PhD ,&nbsp;Ryozo Nagai MD, PhD","doi":"10.1016/j.jacl.2024.07.002","DOIUrl":"10.1016/j.jacl.2024.07.002","url":null,"abstract":"<div><h3>BACKGROUND AND AIMS</h3><div>Previous studies have not found a consistent association between circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and the risk of cardiovascular events partly due to measurement methods that cannot distinguish between uncleaved and furin-cleaved forms of PCSK9.</div></div><div><h3>METHODS</h3><div>This is a prespecified sub-study of the REAL-CAD study which is a prospective, multicenter, randomized trial to compare high- versus low-dose statin in patients with stable coronary artery disease (CAD). The primary endpoint was major adverse cerebrovascular and cardiovascular events (MACCE) defined as a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergency hospitalization. In this case-cohort study, serum mature (uncleaved) and furin-cleaved PCSK9 levels obtained at 6 months after randomization were measured among 426 participants who developed MACCE (cases) and 1,478 randomly selected participants (sub-cohort).</div></div><div><h3>RESULTS</h3><div>From 1,478 patients in the sub-cohort, the Cox proportional hazards models with a pseudolikelihood method for case-cohort design revealed that the risk of the primary endpoint in patients with the highest quartile of mature PCSK9 levels was similar to that in the lowest quartile (hazard ratio [HR] 0.809; 95% confidence intervals [CI], 0.541-1.209). Similarly, the HR for the highest to lowest quartiles of furin-cleaved PCSK9 was 0.948 (95% CI, 0.645-1.392) (<em>P</em> = 0.784). Compared to the lowest quartile, neither serum mature nor furin-cleaved PCSK9 levels predicted MACCE.</div></div><div><h3>CONCLUSIONS</h3><div>In a large-scale secondary prevention cohort, serum mature and furin-cleaved PCSK9 levels did not provide useful information for predicting future cardiovascular events in statin-treated patients with stable CAD.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"18 5","pages":"Pages e844-e854"},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141840704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic association analyses highlight apolipoprotein B as a determinant of chronic kidney disease in patients with type 2 diabetes","authors":"Zhenqian Wang MSc ,&nbsp;Jiaying Zhang MPH ,&nbsp;Feng Jiao PhD ,&nbsp;Yueheng Wu PhD ,&nbsp;Liyuan Han PhD ,&nbsp;Guozhi Jiang PhD","doi":"10.1016/j.jacl.2024.07.004","DOIUrl":"10.1016/j.jacl.2024.07.004","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>Blood lipid levels were associated with chronic kidney disease (CKD) in patients with type 2 diabetes (T2D), but the genetic basis and causal nature remain unclear.</div></div><div><h3>OBJECTIVE</h3><div>This study aimed to investigate the relationships of lipids and their fractions with CKD in patients with T2D.</div></div><div><h3>METHODS</h3><div>Our prospective analysis involved 8,607 White participants with T2D but no CKD at baseline from the UK Biobank. Five common lipid traits were included as exposures. Weighted genetic risk scores (GRSs) for these lipid traits were developed. The causal associations between lipid traits, as well as lipid fractions, and CKD were explored using linear or nonlinear Mendelian randomization (MR). The 10-year predicted probabilities of CKD were evaluated via integrating MR and Cox models.</div></div><div><h3>RESULTS</h3><div>Higher GRS of apolipoprotein B (ApoB) was associated with an increased CKD risk (hazard ratio (HR) [95% confidence interval (CI)]:1.07[1.02,1.13] per SD; <em>P</em> = 0.008) after adjusting for potential confounders. Linear MR indicated a positive association between genetically predicted ApoB levels and CKD (HR [95% CI]:1.53 [1.12,2.09]; <em>P</em> = 0.008), but no evidence of associations was found between other lipid traits and CKD in T2D. Regarding 12 ApoB- containing lipid fractions, a significant causal association was found between medium very-low-density lipoprotein particles and CKD (HR[95% CI]:1.16[1.02,1.32];<em>P</em> = 0.020). Nonlinear MR did not support nonlinearity in these causal associations. The 10-year probability curve showed that ApoB level was positively associated with the risk of CKD in patients with T2D.</div></div><div><h3>CONCLUSION</h3><div>Lower ApoB levels were causally associated with a reduced risk of CKD in patients with T2D, positioning ApoB as a potential therapeutic target for CKD prevention in this population.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"18 5","pages":"Pages e787-e796"},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141852135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}