Lower LDL-C Research Articles

The potential impact of inflammation on the lipid paradox in patients with acute myocardial infarction: a multicenter study

BackgroundLow-density lipoprotein cholesterol (LDL-C) is a well-recognized risk factor for cardiovascular diseases. However, several clinical studies demonstrated an inverse association between LDL-C and mortality risk in patients with acute myocardial infarction (AMI), known as the lipid paradox. This study aims to investigate the potential impact of inflammation on the association between LDL-C levels and mortality risks.MethodsA total of 5244 patients with AMI from a large nationwide prospective cohort were included in our analysis. Patients were stratified according to LDL-C quartiles. The primary outcome was all-cause mortality, and the secondary endpoint was cardiac mortality. High-sensitive C-reactive protein (hsCRP) > 3 mg/L was defined as high inflammatory risk.ResultsDuring a median follow-up of 2.07 years, 297 mortality events (5.5%) and 227 cardiac mortality events (4.2%) occurred. Patients in the lowest LDL-C quartile had the highest incidence of all-cause mortality (7.3%) and cardiac mortality (5.8%). A U-shaped association between LDL-C levels and mortality risk was observed after multivariable adjustment, which persisted only in patients with high hsCRP levels. In contrast, a linear association between LDL-C and mortality risk was shown in patients with low hsCRP levels.ConclusionsAMI patients with lower LDL-C levels had a higher risk of mortality. However, this association was only observed in those with high inflammatory risk. In contrast, the relationship between LDL-C and mortality risk was linear in patients with low inflammatory risk. This suggests the importance of considering inflammation when managing LDL-C levels in AMI patients.

Allopurinol use predicts lower LDL cholesterol in patients with pre-dialysis CKD - a prospective cohort study

Abstract Background Hyperuricemia influences lipid metabolism, yet relationships between urate-lowering therapy with allopurinol, serum urate, and lipid levels in patients with chronic kidney disease (CKD) remain underexplored. Methods This was a post-hoc analysis of 1,970 participants of the CAN AIM to PREVENT who had pre-dialysis CKD and were not receiving lipid-lowering therapy or febuxostat. Joint generalized structural equation modelling was used to investigate associations between allopurinol use (yes or no), serum urate (as a continuous or categorical variable (target if <6 mg/dL or high if ≥6 mg/dL)), and lipid levels (total cholesterol, LDL-C, HDL-C, and triglycerides) assessed every 6 months for up to 3 years, along with time-to-event outcomes (death or initiation of renal replacement therapy), adjusting for demographic and clinical factors. Mediation analysis was used to determine allopurinol's direct and indirect effects (via urate) on lipid levels. Results Allopurinol use independently predicted lower total cholesterol (-7.94%, 95% CI: -12.13% to -3.54%, p<0.001)) and LDL-C (-13.84%, (-21.14 to -5.87), p=0.001). Serum urate independently predicted a small increase in LDL-C (0.02% per mg/dL (0.009 to 0.03), p<0.001). Patients on allopurinol with target urate had lower LDL-C compared to those not on allopurinol with target urate (-4.46% (-8.25 to -0.50), p=0.027) and those on allopurinol with high urate (-10.15% (-13.16 to -7.04), p<0.001. Mediation analysis showed that serum urate indirectly mediated only 24% of the effect of allopurinol on LDL-C. Conclusion Allopurinol use predicted lower total and especially LDL cholesterol independently of serum urate in this cohort of patients with pre-dialysis CKD. Future studies could investigate underlying mechanisms, evaluate clinical implications, and confirm these findings in this and other populations.

Inadequate Intensification of LDL-cholesterol lowering therapy after coronary revascularization: Insights from the GOULD registry.

Patients with a history of coronary revascularization are at a higher risk for subsequent cardiovascular events and all-cause mortality. Lowering LDL-cholesterol (LDL-C) levels post-revascularization significantly reduces these risks. This analysis compared LDL-C-lowering therapies at baseline and over time among patients with and without prior coronary revascularization in the GOULD registry (a prospective multicenter cohort study). Baseline- and 24-month follow-up characteristics-including LDL-C levels and strategies for lipid-lowering therapy (LLT)-were evaluated. Out of 5006 patients, 2195 (43.8%) had prior coronary revascularization. At baseline, these patients had lower LDL-C (99.2 mg/dL vs. 102.5 mg/dL; p < 0.001) and were more likely to be on intensive LLT (52.8% vs. 42.7%; p < 0.001). At 24 months, they had small reductions in LDL-C (-15.6% vs. -13.7%; p = 0.145) and were more likely to be on intensive LLT (61.9% vs. 51.5%; p < 0.001). Similar LDL-C reductions were observed in the PCSK9i group regardless of revascularization status. Despite slightly better baseline LLT among patients with prior revascularization, few patients met the <70 mg/dL goal and LLT was rarely escalated during 24 months of follow-up. Improved systems-based strategies and personalized treatment approaches are urgently needed to enhance LDL-C lowering and reduce cardiovascular events, especially in patients with a history of coronary revascularization.

PCSK9 inhibitors in the research progress of atherosclerotic cardiovascular diseases

Abstract. Atherosclerosis is a major global health issue, with cardiovascular diseases leading to over 4 million deaths in China in 2019. Effective management of atherosclerosis is crucial for reducing its incidence and mortality, with LDL-C reduction being a key strategy. This study examines the role of PCSK9 in atherosclerosis and the therapeutic potential of PCSK9 inhibitors, focusing on their ability to lower LDL-C levels and prevent cardiovascular events A literature review was conducted, analyzing the mechanisms of PCSK9 in lipid metabolism and the efficacy of various PCSK9 inhibitors, including monoclonal antibodies, antisense oligonucleotides, and small interfering RNA. PCSK9 inhibitors, such as Alirocumab, evolocumab, and Inlisiran, have demonstrated effectiveness in reducing LDL-C levels. Inlisiran, in particular, offers a long-lasting effect and has shown significant potential in clinical trials. Nucleic acid-based treatments are emerging as promising options with advantages such as sustained efficacy and a broad application scope, despite the need for further research to address delivery and off-target effects.

PCSK9 and its relationship with HMGB1, TLR4, and TNFα in non-statin and statin-treated coronary artery disease patients.

Despite statin use in coronary artery disease (CAD), significant risk remains, potentially due to increased proprotein convertase subtilisin/kexin-type 9 (PCSK9) production, which raises LDL-C levels and induces inflammation. The exact relationship between PCSK9, inflammatory markers like TNFα, TLR4, CRP, and HMGB1, and monocyte subsets is poorly understood. This study aimed to explore these relationships in non-statin and statin-taking CAD patients. This case-control study included 91 controls and 91 stable CAD patients, divided into no-statin (NS, n = 25), low-dose statin (LDS, n = 25), and high-dose statin (HDS, n = 41) groups. Serum levels of LDL-C, CRP, PCSK9, TLR4, HMGB1, and TNFα were measured. Monocyte subsets were classified using flow cytometry into classical monocytes (CM), intermediate monocytes (IM), and non-classical monocytes (NCM). CAD patients showed elevated PCSK9, LDL-C, and inflammatory markers compared to controls. Statin groups (LDS, HDS) had lower LDL-C and inflammatory markers but higher PCSK9 than the NS group, with the HDS group showing the lowest LDL-C and inflammatory markers but the highest PCSK9. In the NS group, PCSK9 positively correlated with inflammatory markers (HMGB1, TNFα, TLR4, CRP) and monocyte subsets (IM%, NCM%). In the total statin group (LDS + HDS), PCSK9 negatively correlated with HMGB1, TLR4, and NCM%, for each, respectively, and positively with CM%. Multivariable linear regression showed significant associations between PCSK9 and HMGB1, NCM%, and IM% in the NS group, and HMGB1, NCM%, and TLR4 in the total statin group. In conclusion, we recommend combining PCSK9 inhibitors with statins in high-risk CAD patients. This may enhance statin efficacy, reduce LDL-C, and inhibit the TLR4/NF-кB inflammatory pathway, decreasing atherosclerotic inflammation.

Abstract 4136273: A Machine Learning Approach to Simplify Risk Stratification of Patients with Atherosclerotic Cardiovascular Disease

Introduction: The 2018 AHA/ACC/Multisociety Blood Cholesterol Guideline recommends that patients with atherosclerotic cardiovascular disease (ASCVD) be classified as very high-risk (VHR) or not very high-risk (NVHR). This designation is based on the presence of &gt; 2 major ASCVD events (recent acute coronary syndrome [ACS], history of myocardial infarction [MI], history of ischemic stroke, symptomatic peripheral artery disease [PAD]) or 1 major ASCVD event and &gt; 2 high-risk conditions (age ≥65 years, heterozygous familial hypercholesterolemia, history of coronary revascularization, diabetes, hypertension, chronic kidney disease, current smoking, persistently elevated LDL-cholesterol [LDL-C], history of heart failure). While this approach was initially instituted to better predict future ASCVD events alone, more intensive LDL-C lowering is now recommended for those at VHR (LDL-C treatment threshold of 55 mg/dL for VHR patients vs 70 mg/dL for NVHR patients). We aimed to simplify ASCVD risk stratification in patients with clinical ASCVD using machine learning models. Methods: We used electronic health record data (Providence Health system) from 2022 to identify patients with ASCVD based on ICD-10 codes. Patient demographics, comorbidities, and laboratory data stratified patients as VHR or NVHR. Then, a classification and regression tree analysis was performed, with the outcome being VHR classification. Patients were randomly assigned to either the testing or training dataset in equal proportion. Variables in the model included age, sex, race, ethnicity, and the Guideline criteria. Model performance was assessed using misclassification rate and area under the receiver operative curve (AUC). Results: A total of 491,514 patients with ASCVD were included, of which 56% were male, 77% were white, and the mean (SD) age was 72.5 (13.0) years. Over half of patients (59%) were VHR. Those with recent ACS, history of MI, history of ischemic stroke, or PAD were classified as VHR 93%, 92%, 84%, and 91%, respectively. Presence of hypertension in these patients increased the likelihood of being VHR to 97%, 97%, 94%, and 98%, respectively. The misclassification rate and AUC for the testing set were 6.8% and 96.2%, respectively. Conclusions: Most patients with a major ASCVD event and hypertension were found to be VHR. Relying on these two factors alone can help simplify risk assessment. This approach may also help increase use of guideline-recommended LDL-C lowering therapy.

Abstract 4138446: Ceramides Surpass LDL-Cholesterol in Predicting Cardiovascular Mortality in Diabetic and Non-Diabetic Patients

The power of cardiovascular risk prediction is biased by comorbidities (including T2DM), medical treatment, and age, which impact cholesterol levels. Consequently, when applying LDL-C, the true cardiovascular risk of such confounded patients is often underestimated. However, it is not clear whether this constraint for risk prediction may likewise apply to other lipid risk markers in particular ceramides. In this observational cohort study, we recorded cardiovascular mortality for 16 years in 1195 patients. Their median age was 67 years, all of them had a high preexisting cardiovascular risk, 51% were taking statins, and 30% had T2DM. We found a U-shaped association between cardiovascular mortality and LDL-C. We thus stratified the population according to the vertex into high (≥150mg/dL) and lower LDL-C (&lt;150mg/dL) and also according to the T2DM status. A Cox regression analysis revealed that LDL-C failed to predict cardiovascular mortality in any subgroup. In contrast, no U-shaped but a linear association was found for ceramide-based markers. They were able to significantly predict cardiovascular mortality after stratification and even after multivariate adjustment. We thus propose that ceramide-based predictors rather than LDL-C should be applied for a more accurate cardiovascular risk prediction in diabetic and other high-risk patients.

Abstract 4139186: Bempedoic Acid and Limb Outcomes in Statin-Intolerant Patients with Peripheral Artery Disease

Introduction: Patients with peripheral artery disease (PAD) are at high risk of major adverse limb events (MALE) and CV events and have high rates of recurrence of these events. Recently, bempedoic acid was shown to reduce MACE in primary and secondary prevention patients. Whether bempedoic acid reduces the risk of MALE is unknown. Methods: CLEAR Outcomes randomized 13,970 patients to bempedoic acid 180 mg or placebo. A clinical history of PAD was reported by investigators at baseline. Two blinded vascular medicine specialists independently adjudicated all adverse events for limb outcomes including worsening PAD symptoms leading to revascularization, chronic limb threatening ischemia, and acute limb ischemia events with the composite defined as MALE. Outcomes were assessed as time to first event as well as total (including recurrent) events using a negative binomial approach. Results: A total of 1,624 of the enrolled patients had PAD at baseline. Over a median of 41.1 months the rate of first and total MALE events in patients with PAD in the placebo group were 8.3% and 13.7% respectively. Bempedoic acid reduced first MALE events by 36% (HR 0.64, 95% CI 0.44-0.93) with an absolute risk reduction (ARR) of 2.5% and number needed to treat (NNT) of 40, compared to placebo (figure, panel A). Similarly, when considering total events, bempedoic acid reduced MALE by 45% (RR 0.55, 95% CI 0.35 – 0.85, figure panel b). Consistent benefits were observed for MALE in the overall population as well as composites of MACE and MALE in both populations (Figure panel b). There was no evidence of effect modification for the benefit of bempedoic acid for MALE on the basis of PAD at baseline (p-interaction 0.09). Conclusions: Bempedoic acid significantly reduces MALE. Benefits appear potentially greater when considering total (i.e. recurrent) events. These findings support the importance of LDL-C lowering therapy in patients with PAD. In addition, these findings support the early use of therapies with proven MALE benefit, including bempedoic acid, to optimize outcomes in PAD.

Abstract 4127681: Neutrophil-lymphocyte ratio as a marker of cardiovascular outcomes in patients with chronic coronary syndrome

Background: Inflammation is one of the pathophysiological processes involved in the genesis and progression of atherosclerosis and has been increasingly used as a therapeutic target in recent years. The neutrophil-lymphocyte ratio (NLR) is a promptly accessible inflammatory biomarker strongly associated with prognosis in the acute coronary setting. However, there are few data in patients with chronic coronary syndrome (CCS). Objective: Analyze the association between NLR and cardiovascular outcomes in patients with CCS. Methods: Patients with CCS, defined as a previous revascularization procedure (surgical or percutaneous), previous myocardial infarction (MI) or stenosis &gt; 50% in at least one epicardial coronary artery, were included and followed up on an outpatient basis. The NLR was calculated using the baseline blood count. The main outcome was the composite of death, non-fatal myocardial infarction and non-fatal stroke. Results: The study population consisted of 975 patients, with a median age of 65 years and 30% were women. Previous MI was present in 61%, 30% had undergone previous revascularization surgery and 46% had percutaneous coronary intervention. Diabetes was prevalent in 59% and hypertension in 95%. The median NLR was 2.15 (IQR 1.25 - 2.87). Patients with NLR ≥ 2.15, when compared to those with NLR &lt; 2.15, presented more left ventricular (LV) dysfunction (58% vs. 55%; p=0.003) and lower LDL-C serum levels (81 vs. 88 mg/dL; p=0.004). There was no association between NLR and coronary anatomical severity. NLR correlated with age, LDL-C and LV function (p &lt; 0.05 for all). During follow-up, 152 events of the composite primary outcome were registered, with an estimated 3-year incidence of 15.6% in the overall population – higher within patients with NLR ≥ 2.15 when compared to NLR &lt; 2.15 (20% x 14%, p = 0.002), as shown in the figure. In the multivariate analysis, the 3rd quartile of NLR had a 31% higher risk than the 1st quartile (p &lt; 0.05). Conclusion: In this study, the NLR, an easily available inflammatory biomarker, independently correlates with cardiovascular outcomes in a population with CCS.

Iterative random forest-based identification of a novel population with high risk of complications post non-cardiac surgery

Assessing the risk of postoperative cardiovascular events before performing non-cardiac surgery is clinically important. The current risk score systems for preoperative evaluation may not adequately represent a small subset of high-risk populations. Accordingly, this study aimed at applying iterative random forest to analyze combinations of factors that could potentially be clinically valuable in identifying these high-risk populations. To this end, we used the Japan Medical Data Center database, which includes claims data from Japan between January 2005 and April 2021, and employed iterative random forests to extract factor combinations that influence outcomes. The analysis demonstrated that a combination of a prior history of stroke and extremely low LDL-C levels was associated with a high non-cardiac postoperative risk. The incidence of major adverse cardiovascular events in the population characterized by the incidence of previous stroke and extremely low LDL-C levels was 15.43 events per 100 person-30 days [95% confidence interval, 6.66–30.41] in the test data. At this stage, the results only show correlation rather than causation; however, these findings may offer valuable insights for preoperative risk assessment in non-cardiac surgery.

Effect of Alirocumab Monotherapy vs Ezetimibe Plus Statin Therapy on LDL-C Lowering in Veterans With History of ASCVD

Effect of Alirocumab Monotherapy vs Ezetimibe Plus Statin Therapy on LDL-C Lowering in Veterans With History of ASCVD

Engineered extracellular vesicles as nanosponges for lysosomal degradation of PCSK9

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a crucial role in degradation of low-density lipoprotein receptor (LDLR) and PCSK9 inhibition emerges as an attractive strategy for atherosclerosis management. In this study, extracellular vesicles (EVs) were engineered to nanosponges, which could efficiently adsorb and deliver PCSK9 into lysosomes for degradation. Briefly, nanosponges were engineered by modifying EVs with EGF-A/PTGFRN fusion protein (PCSK9 binding domain EGF-A from the mutant LDLR with higher affinity was fused to the C-terminus of Prostaglandin F2 Receptor Negative Regulator). The modification endowed the EVs with hundreds of EGF-A displayed on the surface and thus the capacity to adsorb PCSK9 efficiently. The adsorbed PCSK9 would thus be delivered into lysosomes for degradation when the nanosponges were endocytosed by liver cell, thus releasing endogenous LDLR from degradation. In ApoE-/- mouse model, tail vein injected nanosponges were able to degrade PCSK9, increase LDLR expression, lower LDL-C level, and thus alleviate atherosclerosis. In summary, we here not only develop a novel strategy for PCSK9 inhibition, but also propose a universal method for adsorption and degradation of circulating proteins for disease management.

The role of maintaining lower LDL-C level during statin treatment for advanced CKD patients

Background and aimsDifferent from other high cardiovascular (CV) risks populations, the evidence supporting the CV protective effect of LDL-C reduction with statins in chronic kidney disease (CKD) patients is comparatively scarce. This study is aimed to investigate the role of maintaining lower LDL-C level in advanced CKD patients. MethodsBy using Chang Gung Research Database, on the basis of Taiwan's largest healthcare group, a total of 5367 adult patients newly-diagnosed with stage 4 CKD and receiving statin were extracted and further categorized into three groups based on their LDL-C levels: <70 mg/dL, 70–100 mg/dL, and ≥100 mg/dL. The main outcome is major adverse cardiac and cerebrovascular events (MACCEs), a composite of cardiovascular death, myocardial infarction, and stroke. The inverse probability of treatment weighting was performed to achieve balance of baseline characteristics. ResultsAt 5-year follow-up, the LDL-C < 70 mg/dL group exhibited significantly lower risks of MACCEs (14.3 % vs. 18.7 %, hazard ratio [HR]: 0.77, 95 % CI: 0.69–0.86), cardiovascular death (7.1 % vs. 9.7 %, subdistribution HR [SHR]: 0.75, 95 % CI: 0.65–0.88), ischemic stroke (4.1 % vs. 5.4 %, [SHR]: 0.65, 95 % CI: 0.54–0.79), and new-onset end-stage renal disease requiring chronic dialysis (25.6 % vs. 29.4 %, SHR: 0.87, 95 % CI: 0.80–0.91) compared to LDL-C > 100 mg/dL group. In contrast, the group with LDL-C levels between 70 and 100 did not significantly differ from the group with LDL-C > 100 mg/dL in study outcomes. ConclusionsMaintaining LDL-C lower than 70 mg/dL may be beneficial for cardiovascular protection in advanced CKD patients and a lower LDL-C treatment target may be required as CKD progression.

Beyond LDL-cholesterol: effects of alirocumab on the human apolipoproteome

Abstract Introduction The PACMAN-AMI (Effects of the PCSK9 Antibody Alirocumab on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction) trial enrolled 300 participants with longitudinal plasma samples available at four time points (enrollment, 24 hours, 4 weeks, 52 weeks), of which 266 completed the 52-week follow-up. Purpose Expanding on a previous investigation employing apolipoprotein proteomics in patients with coronary heart disease, the current study aimed to evaluate the impact of the monoclonal antibody alirocumab on apolipoprotein and proprotein convertase subtilisin/kexin type 9 (PCSK9) levels. Methods A mass spectrometry assay was employed to quantify 15 apolipoproteins. Linear mixed-effects models assessed the impact of timepoints and treatments (alirocumab: n = 131, placebo: n = 135, in addition to statins) on apolipoprotein levels. Results Alirocumab led to a fast rise in PCSK9 levels, with a marked increase [inter-quartile range] of 262% [207%] as early as 24 hours after treatment initiation, followed by more pronounced elevations at 4 weeks and 52 weeks, reaching 1575% [813%] and 1480% [747%], respectively (P &amp;lt; 0.001 for all comparisons). At 52 weeks, the ApoB reduction compared with enrollment was -75% [10%] with alirocumab vs. -43% [19%] with placebo (P &amp;lt; 0.001, between groups), while the change in LDL-C was -88% [9%] with alirocumab vs. -54% [19%] with placebo (P &amp;lt; 0.001). Alongside significantly greater reductions in ApoC2 (P = 0.0041) and ApoC3 (P &amp;lt; 0.001) with alirocumab, ApoE changed by -41.6% [21.1%] with alirocumab compared to -15.4% [24.5%] with placebo (P &amp;lt; 0.001). Overall, there was no impact on Apo(a) levels compared to baseline. Conclusion The rapid increase in PCSK9 levels after 24 hours suggests immediate immunocomplex formation. A compensatory rise in PCSK9 production may contribute to later elevations. Alirocumab not only lowered LDL-C but also achieved a sustained reduction in very low-density lipoprotein-associated apolipoproteins (ApoC2, ApoC3, and ApoE), indicating additional benefits of PCSK9 inhibitors.

Impact of allogenic Fecal Microbiota Transplantation (FMT) on lipid parameters in patients with metabolic syndrome (MetS): a meta-analysis

Abstract Background Metabolic Syndrome (MetS) has long been considered a formidable global health concern, and impaired lipid metabolism has been one of its crucial clinical manifestations. Fecal Microbiota Transplantation (FMT) has emerged as a potential therapeutic strategy for MetS, nevertheless, prior meta-analyses have not only yielded conflicting outcomes, but as well predominantly centered on glycemic parameters, leaving the potential impact of FMT on lipid metabolism remained unexplored. Purpose This meta-analysis systematically assessed the influence of allogenic FMT on lipid parameters in MetS patients, unraveling its potential as an innovative therapeutic modality for MetS. Methods A meta-analysis was performed to explore the impact of allogenic FMT on lipid parameters (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol [TCHO] and triglycerides [TG]) in patients with MetS. Terms regarding FMT and metabolic syndrome were searched in PubMed/Medline, EMBASE, Web of Science, the Cochrane Library, and Scopus from the inception of the databases until 31 August 2023. Ten randomized controlled trials (RCTs) were included and mean difference (MD) of parameters were pooled using a fixed effects model. Subgroup analyses according to follow-up durations were performed, and this study was registered in PROSPERO. Results A total of 532 patients in 10 studies were included. Patients undergoing allogenic FMT manifested significantly higher HDL-c level compared with control group (receiving placebo or autologous FMT, pooled MD 0.06 [95% CI: 0.02, 0.10]), and the result remained consistent in the subgroup with 4 to 6 weeks of follow-up (MD 0.07 [95% CI: 0.02, 0.10]). Though overall pooled result did not manifest a significant LDL lowering effect (MD -0.08 [95% CI: -0.21, 0.05]), in subgroup analyses, a significantly lowered LDL level was observed at 12 weeks of follow-up (MD -0.34 [95% CI: -0.60, -0.08]). No significant difference was observed between allogenic FMT and control group concerning TCHO ant TG levels regardless of lengths of follow-up. Conclusions An overall higher level of HDL-C and lowered LDL-C at 12 weeks of follow-up was observed in MetS patients receiving allogenic FMT. The results indicated that gut microbiota from lean, healthy donors may display a beneficial effect on modulating lipid metabolism in patients with MetS. Allogenic FMT manifested promising therapeutic impact and could serve as a viable intervention for MetS patients. Future large-scale RCTs are required for further validation.

Differences in cardiovascular risk in the general population of low and high altitude residents in Peru. HIGH Altitude CArdiovascular REsearch Latin America Population Study (HIGHCARE-LAPS)

Abstract Introduction Living at high altitude (HA) is associated with profound changes in cardiovascular physiology, mostly caused by chronic hypoxia. Available data from high income countries (Switzerland, Austria) suggest beneficial effects of moderate altitude residence in terms of cardiovascular risk. Little is known, however, about cardiovascular risk profile in long-term residents of higher altitudes from low-income countries. Aim To compare cardiovascular risk estimated with validated score in population-based samples of permanent residents of low and high-altitude communities in Peru. Methods Study participants (adults permanently residing at either low or high altitude) were recruited by sex- and age-stratified random multistage cluster sampling from the general population of urban areas at different altitudes in Peru (lowlanders: &amp;lt;500 m above sea level, highlanders: cities at 3287 m, 3824 m and 4330 m). For all participants questionnaire-based information, conventional blood pressure (BP; 3 seated measurements with a validated oscillometric device) and laboratory variables were obtained. Based on the collected data atherosclerotic cardiovascular disease (ASCVD) risk was estimated according to Pooled Cohort Equations (PCE, previously calibrated in South American population). Participants below 40 years of age, with ASVCD history, with LDL-C≥190 mg/dL or on LDL-C lowering therapy were excluded from this analysis. Results The analysis included 146 lowlanders and 373 highlanders, most of whom had low 10-year ASVCD risk, with the median estimated risk being significantly higher among lowlanders. Comparisons between the groups in terms of principal variables of interest are reported in the Table. The highlanders were slightly younger, had lower BMI, conventional BP, HDL cholesterol, lower prevalence of antihypertensive medication and of diabetes, and higher heart rate. In a multivariable model the difference in ASCVD risk between lowlanders and highlanders was significant (p=0.0009) after adjusting for BMI and socio-economic variables but not after systolic BP was included in the model (p=0.800). Conclusions Residence at HA is associated with a lower estimated ASCVD risk in the general population of Peru, mainly because of lower BP levels. Considering that the prognostic value of cardiovascular risk estimates in highland populations is unknown, longitudinal cohort studies would be required to assess whether this finding is associated with a lower rate of cardiovascular events.

Inclisiran-containing low-density lipoprotein cholesterol reduction effectively stabilizes atherosclerotic plaques

Abstract Background/Introduction Near-infrared spectroscopy (NIRS) allows to quantify lipid composition of coronary artery lesions. High plaque lipid content has been associated with increased adverse cardiovascular event risk. Purpose Aim of this study was to evaluate atherosclerotic plaque lipid content reduction in association with low-density lipoprotein (LDL-C) lowering on the background of intensive hypolipidaemic therapy. Methods NIRS investigation was performed in stable coronary artery disease patients having 20-50% stenosis in the proximal or middle third of a coronary artery. Segment of interest was repeatedly evaluated after 15 months. Lipid-rich plaques (LRPs) were defined as lesions with maximum lipid-core burden index within 4 mm (maxLCBI4 mm) &amp;gt;250. Study participants were taking high-intensity statin (atorvastatin 40 or 80 mg and rosuvastatin 20 or 40 mg) with or without ezetimibe for a run-in period of 4-6 weeks. Afterwards, in patients not achieving LDL-C level &amp;lt;1.8 mmol/l, add-on inclisiran was started. Baseline LDL-C was defined as the level at the time of initiation of optimal lipid-lowering therapy. Statistical significance level of 0.05 was set. Results Data of 36 patients was analyzed. Mean baseline maxLCBI4 mm was 203.9, reduced by 39.8% (-81.1, 95%CI -129.2 to -33.0) at 15-month follow-up (P=0.003). In 15 patients LRPs were detected with mean baseline maxLCBI4 mm 363.5, which was decreased by 35.8% (-130.3, 95%CI -235.0 to -25.7) (P=0.020). Mean LDL-C level at baseline was 2.5 mmol/l among all participants, lowered by 32.0% (-0.8, 95%CI -1.1 to -0.5) after 15 months of treatment (P&amp;lt;0.001). 19 patients received inclisiran in addition to high-dose statin and optional ezetimibe therapy. In 24 patients achieving LDL-C target &amp;lt;1.8 mmol/l at 15-month follow-up, a significant maxLCBI4 mm reduction from 208.5 by 48.4% (-101.0, 95%CI -169.3 to -32.7) was established (P=0.010). Among those having LDL-C &amp;gt;1.8 mmol/l, maxLCBI4 mm reduction from 194.7 by 21.2% (-41.25, 95%CI -94.7 to 12.2) was observed, however the change was not statistically significant (P=0.114). Conclusion LDL-C lowering with high-intensity hypolipidaemic therapy, including escalation to proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition, demonstrated atherosclerotic plaque stabilization by NIRS-detected lipid content decrease.

Plasma lipids and glycaemic indices in Australians following plant-based diets versus a meat-eating diet

BackgroundVegan and vegetarian dietary patterns are known to beneficially modulate risk factors for cardiovascular disease; however, the current literature does not differentiate between various plant-based diets. This study aimed to examine the association between various plant-based diets and plasma lipids and glycaemic indices compared to a regular meat-eating diet.MethodsA cross-sectional study of Australian adults (n = 230) aged 30-75yrs habitually consuming the following were recruited: vegan, lacto-vegetarian, pesco-vegetarian, semi-vegetarian, or regular meat-eater. Multivariable regression analysis was used to adjust for covariates.ResultsCompared to regular meat-eaters, vegans had significantly lower total cholesterol (-0.77mmol/L,95% CI -1.15, -0.39, P < 0.001), low-density lipoprotein cholesterol (LDL-C, -0.71mmol/L, 95% CI -1.05, -0.38, P < 0.001), non-high-density lipoprotein cholesterol (non-HDL-C, -0.75mmol/L, 95% CI -1.11, -0.39, P < 0.001), total cholesterol/HDL-C-ratio (-0.49mmol/L, 95% CI -0.87, -0.11, P = 0.012), fasting blood glucose (FBG, -0.29mmol/L, 95% CI -0.53, -0.06, P = 0.014), haemoglobin A1C (-1.85mmol/mol, 95% CI -3.00, -0.71, P = 0.002) and insulin (-1.76mU/L, 95% CI -3.26, -0.26, P = 0.021) concentrations. Semi-vegetarians had significantly lower LDL-C (-0.41mmol/L, 95% CI -0.74, -0.08, P = 0.041) and non-HDL-C (-0.40mmol/L, 95% CI -0.76, -0.05, P = 0.026) and lacto-ovo vegetarians had significantly lower FBG (-0.34mmol/L, 95% CI -0.56, -0.11, P = 0.003) compared to regular meat-eaters. There were no differences in HDL-C and triglycerides between plant-based and regular-meat diets.ConclusionsPlasma lipaemic and glycaemic measures as a collective were more favourable among vegans, whereas among lacto-ovo vegetarians and semi-vegetarians, only some measures were favourable.Trial registrationACTRN12621000743864. Date 6/11/2021.

Efficacy of Vitamin-D supplementation in improving the prognosis of H-type hypertension in elderly patients.

To investigate the correlation between 25-hydroxyvitamin D and H-type hypertension in elderly patients, and to observe the clinical efficacy of vitamin D supplementation in those patients. This was a retrospective study. One hundred and twenty elderly hypertensive patients treated at The Affiliated Hospital of Hebei University from June 2022 to June 2023 were randomly divided into Group-A (n=60) with hypertension and elevated homocysteine (Hcy) levels (H-type hypertension), and Group-B(n=60) with hypertension and normal Hcy levels. Blood levels of 25-hydroxyvitamin D and 24 hours ambulatory blood pressure were assessed in both groups of patients upon admission, with the correlation analysis performed simultaneously. The therapeutic effects were compared between the two groups. Through Pearson correlation analysis, there were negative correlations of serum 25-hydroxyvitamin D levels with 24 hours SSD, 24 hours DSD, dnSBP, and nDBP(all p<0.05). After 12 weeks of treatment, the treatment group had higher 25-hydroxyvitamin D levels and lower 24 hours SBP, 24h DBP, dSBP, dDBP, nSBP, nDBP levels than those of the control group(p<0.05). After treatment, the treatment group had lower blood Hcy, IMT, TC, TG, and LDL-C levels(p<0.05), and higher HDL-C levels(p<0.05) than those of the control group. Serum 25-hydroxyvitamin D levels in elderly patients with H-type hypertension have negative correlations with 24 hours SSD, 24 hours DSD, dnSBP, and nDBP. Oral vitamin D supplementation for H-type hypertensive patients exhibits significant therapeutic effects, with improvements in 24 hours ambulatory blood pressure monitoring results, blood lipid levels, IMT, and blood Hcy levels after treatment.

Genetic and Anthropometric Interplay: How Waist-to-Hip Ratio Modulates LDL-c Levels in Mexican Population.

Genetic factors contribute to the physiopathology of obesity and its comorbidities. This study aimed to investigate the association of the SNPs ABCA1 (rs9282541), ADIPOQ (rs2241766), FTO (rs9939609), GRB14 (rs10195252), and LEPR (rs1805134) with various clinical, anthropometric, and biochemical variables. The study included 396 Mexican mestizo individuals with obesity and 142 individuals with normal weight. Biochemical markers were evaluated from peripheral blood samples, and SNP genotyping was performed using PCR with TaqMan probes. A genetic risk score (GRS) was computed using an additive model. No significant associations were found between the SNPs ABCA1, ADIPOQ, FTO, and LEPR with obesity. However, the T allele of the GRB14 SNP was significantly associated with obesity (χ2 = 5.93, p = 0.01; OR = 1.52; 95% CI: 1.08-2.12). A multivariate linear regression model (adjusted R-squared: 0.1253; p < 0.001) predicting LDL-c levels among all participants (n = 538) identified significant (p < 0.05) beta coefficients for several anthropometric and biochemical variables, as well as for the GRS. Additionally, the interaction between the GRS and the waist-to-hip ratio (WHR) showed a negative beta coefficient (BC = -26.5307; p = 0.014). Participants with a WHR < 0.839 showed no effect of GRS on LDL-c concentration, while those with a WHR > 0.839 exhibited a greater effect of GRS (~9) at lower LDL-c concentrations (~50 mg/dL) and a lesser effect of GRS (~7) at higher LDL-c concentrations (~250 mg/dL). A significant interaction between genetics and WHR influences LDL-c in Mexicans, which may contribute to the prevention and clinical management of dyslipidemia and cardiovascular disease.