Pub Date : 2024-09-01DOI: 10.1016/j.jacl.2024.05.004
Lubo Shi MM , Xiaoduo Liu MM , Enze Li MM , Shutian Zhang MD , Anni Zhou MD
BACKGROUND
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.
METHODS
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.
RESULTS
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, P = 5.615 × 10−5). An HMGCR-mediated increase in LDL-C was significantly associated with the order Pasteurellales (β = 0.489, SE = 0.123, P = 6.955 × 10−5) and the genus Haemophilus (β = 0.491, SE = 0.125, P = 8.379 × 10−5), whereas a PCSK9-mediated increase in LDL-C was associated with the genus Terrisporobacter (β = 0.666, SE = 0.127, P = 1.649 × 10−5). No pleiotropy was detected.
CONCLUSIONS
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.
{"title":"Association of lipid-lowering drugs with gut microbiota: A Mendelian randomization study","authors":"Lubo Shi MM , Xiaoduo Liu MM , Enze Li MM , Shutian Zhang MD , 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<sup>−5</sup>). 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<sup>−5</sup>) and the genus Haemophilus (β = 0.491, SE = 0.125, <em>P</em> = 8.379 × 10<sup>−5</sup>), 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<sup>−5</sup>). 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}
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.
METHODS
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).
RESULTS
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) (P = 0.784). Compared to the lowest quartile, neither serum mature nor furin-cleaved PCSK9 levels predicted MACCE.
CONCLUSIONS
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.
{"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 , Masaomi Gohbara MD, PhD , Kohei Uemura MSc, PhD , Noriaki Iwahashi MD, PhD , Kozo Okada MD, PhD , Hiroshi Iwata MD, PhD , Yoshihiro Fukumoto MD, PhD , Takafumi Hiro MD, PhD , Yukio Ozaki MD, PhD , Satoshi Iimuro MD, PhD , Ichiro Sakuma MD, PhD , Seiji Hokimoto MD, PhD , Katsumi Miyauchi MD, PhD , Yutaka Matsuyama PhD , Yoshihisa Nakagawa MD, PhD , Hisao Ogawa MD, PhD , Hiroyuki Daida MD, PhD , Hiroaki Shimokawa MD, PhD , Yasushi Saito MD, PhD , Takeshi Kimura MD, PhD , 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}
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.
OBJECTIVE
This study aimed to investigate the relationships of lipids and their fractions with CKD in patients with T2D.
METHODS
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.
RESULTS
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; P = 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]; P = 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];P = 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.
CONCLUSION
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.
{"title":"Genetic association analyses highlight apolipoprotein B as a determinant of chronic kidney disease in patients with type 2 diabetes","authors":"Zhenqian Wang MSc , Jiaying Zhang MPH , Feng Jiao PhD , Yueheng Wu PhD , Liyuan Han PhD , 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}
Pub Date : 2024-09-01DOI: 10.1016/j.jacl.2024.05.005
Anandita Agarwala MD , Dave L. Dixon PharmD , Eugenia Gianos MD , Carol F. Kirkpatrick PhD, MPH, RDN , Erin D. Michos MD, MHS , Priyanka Satish MD , Kim K. Birtcher PharmD, MS , Lynne T. Braun PhD, CNP , Priyamvada Pillai MD , Karol Watson MD, PhD , Robert Wild MD, MPH, PhD , Laxmi S. Mehta MD
Cardiovascular disease (CVD) is the leading cause of death among women and its incidence has been increasing recently, particularly among younger women. Across major professional society guidelines, dyslipidemia management remains a central tenet for atherosclerotic CVD prevention for both women and men. Despite this, women, particularly young women, who are candidates for statin therapy are less likely to be treated and less likely to achieve their recommended therapeutic objectives for low-density lipoprotein cholesterol (LDL-C) levels. Elevated LDL-C and triglycerides are the two most common dyslipidemias that should be addressed during pregnancy due to the increased risk for adverse pregnancy outcomes, such as preeclampsia, gestational diabetes mellitus, and pre-term delivery, as well as pancreatitis in the presence of severe hypertriglyceridemia. In this National Lipid Association Expert Clinical Consensus, we review the roles of nutrition, physical activity, and pharmacotherapy as strategies to address elevated levels of LDL-C and/or triglycerides among women of reproductive age. We include a special focus on points to consider during the shared decision-making discussion regarding pharmacotherapy for dyslipidemia during preconception planning, pregnancy, and lactation.
{"title":"Dyslipidemia management in women of reproductive potential: An Expert Clinical Consensus from the National Lipid Association","authors":"Anandita Agarwala MD , Dave L. Dixon PharmD , Eugenia Gianos MD , Carol F. Kirkpatrick PhD, MPH, RDN , Erin D. Michos MD, MHS , Priyanka Satish MD , Kim K. Birtcher PharmD, MS , Lynne T. Braun PhD, CNP , Priyamvada Pillai MD , Karol Watson MD, PhD , Robert Wild MD, MPH, PhD , Laxmi S. Mehta MD","doi":"10.1016/j.jacl.2024.05.005","DOIUrl":"10.1016/j.jacl.2024.05.005","url":null,"abstract":"<div><div>Cardiovascular disease (CVD) is the leading cause of death among women and its incidence has been increasing recently, particularly among younger women. Across major professional society guidelines, dyslipidemia management remains a central tenet for atherosclerotic CVD prevention for both women and men. Despite this, women, particularly young women, who are candidates for statin therapy are less likely to be treated and less likely to achieve their recommended therapeutic objectives for low-density lipoprotein cholesterol (LDL-C) levels. Elevated LDL-C and triglycerides are the two most common dyslipidemias that should be addressed during pregnancy due to the increased risk for adverse pregnancy outcomes, such as preeclampsia, gestational diabetes mellitus, and pre-term delivery, as well as pancreatitis in the presence of severe hypertriglyceridemia. In this National Lipid Association Expert Clinical Consensus, we review the roles of nutrition, physical activity, and pharmacotherapy as strategies to address elevated levels of LDL-C and/or triglycerides among women of reproductive age. We include a special focus on points to consider during the shared decision-making discussion regarding pharmacotherapy for dyslipidemia during preconception planning, pregnancy, and lactation.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"18 5","pages":"Pages e664-e684"},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141186565","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}
Pub Date : 2024-09-01DOI: 10.1016/j.jacl.2024.07.012
Jillian D'Souza BS, Daniel E. Soffer MD, Archna Bajaj MD, MSCE
Guidelines recommend checking lipoprotein(a) [Lp(a)] levels in patients at high-risk for cardiovascular disease, with more recent recommendations advocating for universal screening in all adults. A brief electronic survey was distributed to select groups of University of Pennsylvania Health System (UPHS) providers, including Internal Medicine and Cardiology physicians and advance practice providers, to understand the current attitudes and barriers to testing for Lp(a). Of the 126 survey respondents, only 31% answered that they test for Lp(a) regularly in their practice. Presence of ASCVD and a family history of ASCVD were the most common reasons for testing. Most survey respondents (69%) replied that they do not currently check Lp(a) levels in patients. The most common reasons provided included lack of familiarity with Lp(a), insurance/ billing concerns, lack of clinical trial outcomes data, and lack of available pharmaceutical interventions. Results from ongoing clinical trials of novel Lp(a)-lowering therapies, if successful, may address provider hesitation toward Lp(a)-testing, but there remains a large gap to fill in awareness of Lp(a).
{"title":"Attitudes and barriers to lipoprotein(a) testing: A survey of providers at the University of Pennsylvania Health System","authors":"Jillian D'Souza BS, Daniel E. Soffer MD, Archna Bajaj MD, MSCE","doi":"10.1016/j.jacl.2024.07.012","DOIUrl":"10.1016/j.jacl.2024.07.012","url":null,"abstract":"<div><div>Guidelines recommend checking lipoprotein(a) [Lp(a)] levels in patients at high-risk for cardiovascular disease, with more recent recommendations advocating for universal screening in all adults. A brief electronic survey was distributed to select groups of University of Pennsylvania Health System (UPHS) providers, including Internal Medicine and Cardiology physicians and advance practice providers, to understand the current attitudes and barriers to testing for Lp(a). Of the 126 survey respondents, only 31% answered that they test for Lp(a) regularly in their practice. Presence of ASCVD and a family history of ASCVD were the most common reasons for testing. Most survey respondents (69%) replied that they do not currently check Lp(a) levels in patients. The most common reasons provided included lack of familiarity with Lp(a), insurance/ billing concerns, lack of clinical trial outcomes data, and lack of available pharmaceutical interventions. Results from ongoing clinical trials of novel Lp(a)-lowering therapies, if successful, may address provider hesitation toward Lp(a)-testing, but there remains a large gap to fill in awareness of Lp(a).</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"18 5","pages":"Pages e873-e876"},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141948097","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}
Coronary microvascular dysfunction (CMD) is associated with angina symptoms and adverse clinical outcomes in patients without obstructive coronary artery disease (CAD). Malondialdehyde-modified low-density lipoprotein (MDA-LDL) is reportedly a marker of the initiation and acceleration of epicardial coronary atherosclerosis. However, its impact on CMD remains unclear.
OBJECTIVE
We aimed to investigate the relationship between CMD and MDA-LDL levels.
METHODS
This study included 95 patients who did not receive lipid-lowering medications and had no obstructive CAD. Obstructive CAD was defined as >50% diameter reduction on coronary angiography or fractional flow reserve of ≤0.80. We retrospectively analyzed coronary flow reserve (CFR), index of microcirculatory resistance (IMR), and MDA-LDL levels. CMD was defined as either CFR <2.0 or IMR ≥25.
RESULTS
CMD was observed in 29 (31%) patients. MDA-LDL levels were significantly higher in patients with CMD than in those without CMD (124.8 ± 37.6 vs. 95.3 ± 29.5 U/L; p < 0.01). Univariable logistic regression analysis indicated a significant relationship between CMD and MDA-LDL levels (odds ratio (OR): 1.03; p < 0.01). In the multivariable model, MDA-LDL levels were significantly associated with CMD (OR: 1.02; p < 0.01). Regression analysis showed a significant correlation between MDA-LDL levels and CFR (r = -0.42, p < 0.01) and IMR (r = 0.35, p < 0.01). In the multiple regression analysis, MDA-LDL levels were independently associated with CFR (β = -0.30, p < 0.01) and IMR (β = 0.26, p = 0.02).
CONCLUSION
MDA-LDL levels were associated with CMD in patients without obstructive CAD.
{"title":"Increased circulating levels of malondialdehyde-modified low-density lipoprotein in patients with coronary microvascular dysfunction","authors":"Tsuyoshi Ito MD, Masashi Yokoi MD, Shuichi Kitada MD, Yu Kawada MD, Tatsuya Mizoguchi MD, Shohei Kikuchi MD, Toshihiko Goto MD, Yoshihiro Seo MD","doi":"10.1016/j.jacl.2024.08.002","DOIUrl":"10.1016/j.jacl.2024.08.002","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>Coronary microvascular dysfunction (CMD) is associated with angina symptoms and adverse clinical outcomes in patients without obstructive coronary artery disease (CAD). Malondialdehyde-modified low-density lipoprotein (MDA-LDL) is reportedly a marker of the initiation and acceleration of epicardial coronary atherosclerosis. However, its impact on CMD remains unclear.</div></div><div><h3>OBJECTIVE</h3><div>We aimed to investigate the relationship between CMD and MDA-LDL levels.</div></div><div><h3>METHODS</h3><div>This study included 95 patients who did not receive lipid-lowering medications and had no obstructive CAD. Obstructive CAD was defined as >50% diameter reduction on coronary angiography or fractional flow reserve of ≤0.80. We retrospectively analyzed coronary flow reserve (CFR), index of microcirculatory resistance (IMR), and MDA-LDL levels. CMD was defined as either CFR <2.0 or IMR ≥25.</div></div><div><h3>RESULTS</h3><div>CMD was observed in 29 (31%) patients. MDA-LDL levels were significantly higher in patients with CMD than in those without CMD (124.8 ± 37.6 vs. 95.3 ± 29.5 U/L; <em>p</em> < 0.01). Univariable logistic regression analysis indicated a significant relationship between CMD and MDA-LDL levels (odds ratio (OR): 1.03; <em>p</em> < 0.01). In the multivariable model, MDA-LDL levels were significantly associated with CMD (OR: 1.02; <em>p</em> < 0.01). Regression analysis showed a significant correlation between MDA-LDL levels and CFR (r = -0.42, <em>p</em> < 0.01) and IMR (r = 0.35, <em>p</em> < 0.01). In the multiple regression analysis, MDA-LDL levels were independently associated with CFR (β = -0.30, <em>p</em> < 0.01) and IMR (β = 0.26, <em>p</em> = 0.02).</div></div><div><h3>CONCLUSION</h3><div>MDA-LDL levels were associated with CMD in patients without obstructive CAD.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"18 5","pages":"Pages e756-e763"},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142190944","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}
Pub Date : 2024-09-01DOI: 10.1016/j.jacl.2024.08.013
Daniel E. Soffer MD , Nicholas A. Marston MD, MPH , Kevin C. Maki PhD , Terry A. Jacobson MD , Vera A. Bittner MD, MSPH , Jessica M. Peña MD, MPH , George Thanassoulis MD, MSc , Seth S. Martin MD, MHS , Carol F. Kirkpatrick PhD, MPH, RDN , Salim S. Virani MD, PhD , Dave L. Dixon PharmD , Christie M. Ballantyne MD , Alan T. Remaley MD, PhD
This National Lipid Association (NLA) Expert Clinical Consensus provides an overview of the physiologic and clinical considerations regarding the role of apolipoprotein B (apoB) measurement to guide clinical care based on the available scientific evidence and expert opinion. ApoB represents the total concentration of atherogenic lipoprotein particles in the circulation and more accurately reflects the atherogenic burden of lipoproteins when compared to low-density lipoprotein cholesterol (LDL-C). ApoB is a validated clinical measurement that augments the information found in a standard lipoprotein lipid panel; therefore, there is clinical value in using apoB in conjunction with a standard lipoprotein lipid profile when assessing risk and managing lipid-lowering therapy (LLT). ApoB has been shown to be superior to LDL-C in risk assessment both before and during treatment with LLT. In individuals, there can be discordance between levels of LDL-C and apoB, as well as LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C), despite high levels of population-wide correlation. When there is discordance between LDL-C and apoB, or LDL-C and non-HDL-C, atherosclerotic cardiovascular disease risk generally aligns better with apoB or non-HDL-C. Additionally, apoB can be used in tandem with standard lipoprotein lipid measurements to diagnose distinct lipoprotein phenotypes. ApoB testing can inform clinical prognosis and care, as well as enable family cascade screening, when an inherited lipoprotein syndrome is identified. The NLA and other organizations will continue to educate clinicians about the role of apoB measurement in improving clinical risk assessment and dyslipidemia management. An urgent need exists to improve access and reimbursement for apoB testing.
美国国家血脂协会 (NLA) 专家临床共识概述了有关载脂蛋白 B（apoB）测量作用的生理学和临床考虑因素，以现有科学证据和专家意见为基础指导临床治疗。载脂蛋白 B 代表血液循环中致动脉粥样硬化脂蛋白颗粒的总浓度，与低密度脂蛋白胆固醇 (LDL-C) 相比，它能更准确地反映脂蛋白的致动脉粥样硬化负担。载脂蛋白B是一种经过验证的临床测量方法，可增强标准脂蛋白血脂组合中的信息；因此，在评估风险和管理降脂治疗（LLT）时，将载脂蛋白B与标准脂蛋白血脂组合结合使用具有临床价值。在使用 LLT 治疗前和治疗期间，载脂蛋白在风险评估中的作用均优于 LDL-C。在个体中，低密度脂蛋白胆固醇和载脂蛋白B以及低密度脂蛋白胆固醇和非高密度脂蛋白胆固醇（non-HDL-C）的水平可能不一致，尽管整个人群的相关性很高。当低密度脂蛋白胆固醇与载脂蛋白B或低密度脂蛋白胆固醇与非高密度脂蛋白胆固醇之间存在不一致时，动脉粥样硬化性心血管疾病风险通常与载脂蛋白B或非高密度脂蛋白胆固醇更为一致。此外，载脂蛋白B可与标准脂蛋白血脂测量同时使用，以诊断不同的脂蛋白表型。当发现遗传性脂蛋白综合征时，载脂蛋白B检测可为临床预后和护理提供依据，并可进行家族串联筛查。NLA 和其他组织将继续向临床医生宣传载脂蛋白 B 检测在改善临床风险评估和血脂异常管理中的作用。目前迫切需要改善载脂蛋白 B 检测的可及性和报销情况。
{"title":"Role of apolipoprotein B in the clinical management of cardiovascular risk in adults: An Expert Clinical Consensus from the National Lipid Association","authors":"Daniel E. Soffer MD , Nicholas A. Marston MD, MPH , Kevin C. Maki PhD , Terry A. Jacobson MD , Vera A. Bittner MD, MSPH , Jessica M. Peña MD, MPH , George Thanassoulis MD, MSc , Seth S. Martin MD, MHS , Carol F. Kirkpatrick PhD, MPH, RDN , Salim S. Virani MD, PhD , Dave L. Dixon PharmD , Christie M. Ballantyne MD , Alan T. Remaley MD, PhD","doi":"10.1016/j.jacl.2024.08.013","DOIUrl":"10.1016/j.jacl.2024.08.013","url":null,"abstract":"<div><div>This National Lipid Association (NLA) Expert Clinical Consensus provides an overview of the physiologic and clinical considerations regarding the role of apolipoprotein B (apoB) measurement to guide clinical care based on the available scientific evidence and expert opinion. ApoB represents the total concentration of atherogenic lipoprotein particles in the circulation and more accurately reflects the atherogenic burden of lipoproteins when compared to low-density lipoprotein cholesterol (LDL-C). ApoB is a validated clinical measurement that augments the information found in a standard lipoprotein lipid panel; therefore, there is clinical value in using apoB in conjunction with a standard lipoprotein lipid profile when assessing risk and managing lipid-lowering therapy (LLT). ApoB has been shown to be superior to LDL-C in risk assessment both before and during treatment with LLT. In individuals, there can be discordance between levels of LDL-C and apoB, as well as LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C), despite high levels of population-wide correlation. When there is discordance between LDL-C and apoB, or LDL-C and non-HDL-C, atherosclerotic cardiovascular disease risk generally aligns better with apoB or non-HDL-C. Additionally, apoB can be used in tandem with standard lipoprotein lipid measurements to diagnose distinct lipoprotein phenotypes. ApoB testing can inform clinical prognosis and care, as well as enable family cascade screening, when an inherited lipoprotein syndrome is identified. The NLA and other organizations will continue to educate clinicians about the role of apoB measurement in improving clinical risk assessment and dyslipidemia management. An urgent need exists to improve access and reimbursement for apoB testing.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"18 5","pages":"Pages e647-e663"},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142224761","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}
Pub Date : 2024-09-01DOI: 10.1016/j.jacl.2024.07.011
Gemme Campbell-Salome PhD , Kelly M. Morgan MS , Jazmine Gabriel PhD , Mary P. McGowan MD , Nicole L. Walters BS , Andrew Brangan BS , Eric P. Tricou MS , Alanna K. Rahm PhD , Amy C. Sturm MS , Laney K. Jones PharmD, MPH
BACKGROUND
Cascade testing can be highly effective in identifying individuals with familial hypercholesterolemia (FH) and help prevent atherosclerotic cardiovascular disease. The IMPACT-FH cascade testing program offered multiple optimized implementation strategies to improve FH cascade testing uptake.
OBJECTIVE
Guided by the Conceptual Model of Implementation Research, this study assessed the IMPACT-FH cascade testing program's implementation outcomes.
METHODS
Implementation outcomes were assessed qualitatively and quantitatively. Interviews were conducted with 33 IMPACT-FH program participants including 15 probands, 12 relatives, and 6 healthcare professionals (HCPs). Transcripts were analyzed using thematic analysis to investigate implementation outcomes. Descriptive statistics were analyzed for scaled implementation outcome measures asked after interviews.
RESULTS
Participants described adopting strategies offered in the IMPACT-FH program because they presented an opportunity to pursue low-cost FH cascade testing. Participants identified barriers to feasibility including: the complexity of disclosing an FH result and offering strategies, inherent limitations of probands choosing strategies, confusion over testing costs, limitations sharing with relatives’ clinicians, discomfort with chatbot technology, and concerns about the workload for HCPs. Participants evaluated the program positively regarding its appropriateness (Mean (M) = 4.70, Standard Deviation (SD) = 0.41), acceptability (M = 4.79, SD = 0.40), and feasibility (M = 4.24, SD = 0.53).
CONCLUSION
The IMPACT-FH cascade testing program and its strategies were evaluated as valuable to adopt and highly appropriate, acceptable, and feasible by participants. Participants identified areas to enhance the program that could improve FH cascade testing uptake.
{"title":"Utilizing innovative implementation strategies for familial hypercholesterolemia: Implementation outcomes from the IMPACT-FH study","authors":"Gemme Campbell-Salome PhD , Kelly M. Morgan MS , Jazmine Gabriel PhD , Mary P. McGowan MD , Nicole L. Walters BS , Andrew Brangan BS , Eric P. Tricou MS , Alanna K. Rahm PhD , Amy C. Sturm MS , Laney K. Jones PharmD, MPH","doi":"10.1016/j.jacl.2024.07.011","DOIUrl":"10.1016/j.jacl.2024.07.011","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>Cascade testing can be highly effective in identifying individuals with familial hypercholesterolemia (FH) and help prevent atherosclerotic cardiovascular disease. The IMPACT-FH cascade testing program offered multiple optimized implementation strategies to improve FH cascade testing uptake.</div></div><div><h3>OBJECTIVE</h3><div>Guided by the Conceptual Model of Implementation Research, this study assessed the IMPACT-FH cascade testing program's implementation outcomes.</div></div><div><h3>METHODS</h3><div>Implementation outcomes were assessed qualitatively and quantitatively. Interviews were conducted with 33 IMPACT-FH program participants including 15 probands, 12 relatives, and 6 healthcare professionals (HCPs). Transcripts were analyzed using thematic analysis to investigate implementation outcomes. Descriptive statistics were analyzed for scaled implementation outcome measures asked after interviews.</div></div><div><h3>RESULTS</h3><div>Participants described adopting strategies offered in the IMPACT-FH program because they presented an opportunity to pursue low-cost FH cascade testing. Participants identified barriers to feasibility including: the complexity of disclosing an FH result and offering strategies, inherent limitations of probands choosing strategies, confusion over testing costs, limitations sharing with relatives’ clinicians, discomfort with chatbot technology, and concerns about the workload for HCPs. Participants evaluated the program positively regarding its appropriateness (Mean (M) = 4.70, Standard Deviation (SD) = 0.41), acceptability (M = 4.79, SD = 0.40), and feasibility (M = 4.24, SD = 0.53).</div></div><div><h3>CONCLUSION</h3><div>The IMPACT-FH cascade testing program and its strategies were evaluated as valuable to adopt and highly appropriate, acceptable, and feasible by participants. Participants identified areas to enhance the program that could improve FH cascade testing uptake.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"18 5","pages":"Pages e832-e843"},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141948099","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}
Pub Date : 2024-09-01DOI: 10.1016/j.jacl.2024.04.134
Friederike Schumann MD , Ursula Kassner MD , Dominik Spira MD , Felix F. Zimmermann MD , Thomas Bobbert MD , Elisabeth Steinhagen-Thiessen MD , Tim Hollstein MD
BACKGROUND
Elevated lipoprotein(a) (Lp(a)) is an established risk factor for cardiovascular disease (CVD). To date, the only approved treatment to lower Lp(a) is lipoprotein apheresis (LA). Previous studies have demonstrated that LA is effective in reducing cardiovascular (CV) risk in patients with elevated low-density lipoprotein cholesterol (LDL-C) and/or Lp(a). Here we report our long-term experience with LA and its effectiveness in reducing CVD events in patients with elevated Lp(a).
METHODS
This retrospective open-label, single-center study included 25 individuals with Lp(a) elevation >60 mg/dL and LDL-C < 2.59 mmol/L who had indication for LA. The primary endpoint of this study was the incidence of any CV event (determined by medical records) after initiation of LA.
RESULTS
Mean LA treatment duration was 7.1 years (min-max: 1–19 years). Median Lp(a) was reduced from 95.0 to 31.1 mg/dL after LA (-67.3%, p < 0.0001). Mean LDL-C was reduced from 1.85 to 0.76 mmol/L after LA (-58.9%, p < 0.0001). Prior to LA, 81 CV events occurred in total (0.87 events/patient/year). During LA, 49 CV events occurred in total (0.24 events/patient/year; -0.63, p = 0.001). Yearly major adverse cardiac event (MACE) rate was reduced from 0.34 to 0.006 (-0.33, p = 0.0002). Similar results were obtained when considering only individuals with baseline LDL-C below 1.42 mmol/L.
CONCLUSION
In this observational study of a heterogeneous CV high-risk cohort with elevated Lp(a), LA reduced Lp(a) levels and was paralleled by a decrease in CV events and MACE. We recommend LA for patients with high Lp(a) who still have CV events despite optimal lipid-lowering medication and lifestyle changes.
{"title":"Long-term lipoprotein apheresis reduces cardiovascular events in high-risk patients with isolated lipoprotein(a) elevation","authors":"Friederike Schumann MD , Ursula Kassner MD , Dominik Spira MD , Felix F. Zimmermann MD , Thomas Bobbert MD , Elisabeth Steinhagen-Thiessen MD , Tim Hollstein MD","doi":"10.1016/j.jacl.2024.04.134","DOIUrl":"10.1016/j.jacl.2024.04.134","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>Elevated lipoprotein(a) (Lp(a)) is an established risk factor for cardiovascular disease (CVD). To date, the only approved treatment to lower Lp(a) is lipoprotein apheresis (LA). Previous studies have demonstrated that LA is effective in reducing cardiovascular (CV) risk in patients with elevated low-density lipoprotein cholesterol (LDL-C) and/or Lp(a). Here we report our long-term experience with LA and its effectiveness in reducing CVD events in patients with elevated Lp(a).</div></div><div><h3>METHODS</h3><div>This retrospective open-label, single-center study included 25 individuals with Lp(a) elevation >60 mg/dL and LDL-C < 2.59 mmol/L who had indication for LA. The primary endpoint of this study was the incidence of any CV event (determined by medical records) after initiation of LA.</div></div><div><h3>RESULTS</h3><div>Mean LA treatment duration was 7.1 years (min-max: 1–19 years). Median Lp(a) was reduced from 95.0 to 31.1 mg/dL after LA (-67.3%, <em>p</em> < 0.0001). Mean LDL-C was reduced from 1.85 to 0.76 mmol/L after LA (-58.9%, <em>p</em> < 0.0001). Prior to LA, 81 CV events occurred in total (0.87 events/patient/year). During LA, 49 CV events occurred in total (0.24 events/patient/year; -0.63, <em>p</em> = 0.001). Yearly major adverse cardiac event (MACE) rate was reduced from 0.34 to 0.006 (-0.33, <em>p</em> = 0.0002). Similar results were obtained when considering only individuals with baseline LDL-C below 1.42 mmol/L.</div></div><div><h3>CONCLUSION</h3><div>In this observational study of a heterogeneous CV high-risk cohort with elevated Lp(a), LA reduced Lp(a) levels and was paralleled by a decrease in CV events and MACE. We recommend LA for patients with high Lp(a) who still have CV events despite optimal lipid-lowering medication and lifestyle changes.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"18 5","pages":"Pages e738-e745"},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140933944","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}
Pub Date : 2024-09-01DOI: 10.1016/j.jacl.2024.07.001
François Mach MD , Frank L.J. Visseren MD , Nilo B. Cater MD , Nejoua Salhi MD , Jarkko Soronen MD , Kausik K. Ray MD , Victoria Delgado MD , J. Wouter Jukema MD , Ulrich Laufs MD , Jose-Luis Zamorano MD , Emilio Ros MD , Jogchum Plat MD , Akos Gabor Gesztes BPharm , Lale Tokgozoglu MD , Chris Packard MD , Peter Libby MD
Cardiovascular (CV) disease is the most common cause of death in Europe. Despite proven benefits, use of lipid-lowering therapy remains suboptimal. Treatment goals are often not achieved, even in patients at high risk with atherosclerotic CV disease (ASCVD).
The occurrence of CV events in patients on lipid-lowering drugs is defined as “residual risk”, and can result from inadequate control of plasma lipids or blood pressure, inflammation, diabetes, and environmental hazards. Assessment of CV risk factors and vascular imaging can aid in the evaluation and management decisions for individual patients.
Lifestyle measures remain the primary intervention for lowering CV risk. Where drug therapies are required to reach lipid treatment targets, their effectiveness increases when they are combined with lifestyle measures delivered through formal programs. However, lipid drug dosage and poor adherence to treatment remain major obstacles to event-free survival.
This article discusses guideline-supported treatment algorithms beyond statin therapy that can help reduce residual risk in specific patient profiles while also likely resulting in substantial healthcare savings through better patient management and treatment adherence.
{"title":"Addressing residual risk beyond statin therapy: New targets in the management of dyslipidaemias–A report from the European Society of Cardiology Cardiovascular Round Table","authors":"François Mach MD , Frank L.J. Visseren MD , Nilo B. Cater MD , Nejoua Salhi MD , Jarkko Soronen MD , Kausik K. Ray MD , Victoria Delgado MD , J. Wouter Jukema MD , Ulrich Laufs MD , Jose-Luis Zamorano MD , Emilio Ros MD , Jogchum Plat MD , Akos Gabor Gesztes BPharm , Lale Tokgozoglu MD , Chris Packard MD , Peter Libby MD","doi":"10.1016/j.jacl.2024.07.001","DOIUrl":"10.1016/j.jacl.2024.07.001","url":null,"abstract":"<div><div>Cardiovascular (CV) disease is the most common cause of death in Europe. Despite proven benefits, use of lipid-lowering therapy remains suboptimal. Treatment goals are often not achieved, even in patients at high risk with atherosclerotic CV disease (ASCVD).</div><div>The occurrence of CV events in patients on lipid-lowering drugs is defined as “<em>residual risk</em>”, and can result from inadequate control of plasma lipids or blood pressure, inflammation, diabetes, and environmental hazards. Assessment of CV risk factors and vascular imaging can aid in the evaluation and management decisions for individual patients.</div><div>Lifestyle measures remain the primary intervention for lowering CV risk. Where drug therapies are required to reach lipid treatment targets, their effectiveness increases when they are combined with lifestyle measures delivered through formal programs. However, lipid drug dosage and poor adherence to treatment remain major obstacles to event-free survival.</div><div>This article discusses guideline-supported treatment algorithms beyond statin therapy that can help reduce residual risk in specific patient profiles while also likely resulting in substantial healthcare savings through better patient management and treatment adherence.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"18 5","pages":"Pages e685-e700"},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141611952","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}
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