Atherosclerosis plus最新文献

Nicotinamide adenine dinucleotide (NAD+) is a central and pleiotropic metabolite involved in cellular energy metabolism, cell signaling, DNA repair, and protein modifications. Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Metabolic stress and aging directly affect the cardiovascular system. Compelling data suggest that NAD + levels decrease with age, obesity, and hypertension, which are all notable risk factors for CVD. In addition, the therapeutic elevation of NAD + levels reduces chronic low-grade inflammation, reactivates autophagy and mitochondrial biogenesis, and enhances oxidative metabolism in vascular cells of humans and rodents with vascular disorders. In preclinical models, NAD + boosting can also expand the health span, prevent metabolic syndrome, and decrease blood pressure. Moreover, NAD + storage by genetic, pharmacological, or natural dietary NAD + -increasing strategies has recently been shown to be effective in improving the pathophysiology of cardiac and vascular health in different animal models, and human health. Here, we review and discuss NAD + -related mechanisms pivotal for vascular health and summarize recent experimental evidence in NAD + research directly related to vascular disease, including atherosclerosis, and coronary artery disease. Finally, we comparatively assess distinct NAD + precursors for their clinical efficacy and the efficiency of NAD + elevation in the treatment of major CVD. These findings may provide ideas for new therapeutic strategies to prevent and treat CVD in the clinic.

Background and aims

Cardiovascular disease (CVD) poses significant health challenges globally. While substantial data exists for most populations, the Arctic Inuit's CVD incidence rates remain understudied. This research aimed to change this by estimating CVD incidence and mortality rates in Greenland from 1994 to 2021.

Methods

Using nationwide registers, a retrospective observational study was conducted, focusing on individuals born in Greenland to Greenlandic-born parents. Data were sourced from the Greenlandic Hospital Discharge Register and the nationwide electronic medical record.

Results

A total of 65,824 individuals were included. the age- and sex-specific incidence rates (IR) of ischemic heart disease, stroke, and heart failure (HF) declined from 1994 to 2021, with the most substantial decline observed for HF among women. Conversely, the IR of atrial fibrillation/flutter increased in both men and women, while the IR of myocardial infarction rose among men. The IR for stroke was particularly elevated compared to other CVD subgroups. Mortality rates for those diagnosed with CVD were 2.4 times higher than those without. Men exhibited a 40 % elevated mortality risk relative to women.

Conclusion

The study provides pivotal insights into CVD trends within the Arctic Inuit population, highlighting both positive developments and areas of concern. Given the increasing elderly demographic in Greenland, proactive health strategies are crucial. Emphasizing primary prevention and addressing specific CVD risks, particularly the elevated stroke IR, is imperative for future public health efforts.

Background and aims

Severe hypertriglyceridemia (HTG), defined as plasma triglyceride (TG) concentration > 10 mmol/L, is relatively uncommon, and its implications for atherosclerotic cardiovascular disease (ASCVD) risk remain somewhat unclear. We evaluated the association between severe HTG and carotid intima-media thickness (IMT), a marker for ASCVD.

Methods

We studied three clinical cohorts: 88 patients with severe HTG (mean TG level 20.6 mmol/L), 271 patients with familial hypercholesterolemia (FH) as a contrast group, and 70 normolipidemic controls. Carotid IMT was measured using standardized ultrasound imaging. Statistical analysis was conducted using one-way analysis of variance (ANOVA) to compare mean IMT values, analysis of covariance (ANCOVA) to adjust for confounding variables, specifically age and sex, as well as Spearman pairwise correlation analysis between variables.

Results

Unadjusted mean carotid IMT was greater in severe HTG and FH groups compared to controls, however, this was no longer significant for severe HTG after adjustment for age and sex. In contrast, adjusted carotid IMT remained significantly different between the FH and control groups.

Conclusions

Our findings suggest that extreme TG elevations in severe HTG patients are not significantly associated with carotid IMT, in contrast to the increased IMT seen in FH patients. These findings add perspective to the complex relationship between severe HTG and ASCVD risk.

Background and aims

Randomized clinical trials have demonstrated the ability of glucagon-like peptide-1 analogues (GLP-1RAs) to reduce atherosclerotic cardiovascular disease events in patients with type 2 diabetes (T2D). How GLP-1RAs modulate diabetic atherosclerosis remains to be determined yet.

Methods

The OPTIMAL study was a prospective randomized controlled study to compare the efficacy of 48-week continuous glucose monitoring- and HbA1c-guided glycemic control on near infrared spectroscopty (NIRS)/intravascular ultrasound (IVUS)-derived plaque measures in 94 statin-treated patients with T2D (jRCT1052180152, UMIN000036721). Of these, 78 patients with evaluable serial NIRS/IVUS images were analyzed to compare plaque measures between those treated with (n = 16) and without GLP-1RAs (n = 72).

Results

All patients received a statin, and on-treatment LDL-C levels were similar between the groups (66.9 ± 11.6 vs. 68.1 ± 23.2 mg/dL, p = 0.84). Patients receiving GLP-1RAs demonstrated a greater reduction of HbA1c [-1.0 (-1.4 to −0.5) vs. −0.4 (-0.6 to −0.2)%, p = 0.02] and were less likely to demonstrate a glucose level >180 mg/dL [-7.5 (-14.9 to −0.1) vs. 1.1 (-2.0 - 4.2)%, p = 0.04], accompanied by a significant decrease in remnant cholesterol levels [-3.8 (-6.3 to −1.3) vs. −0.1 (-0.8 - 1.1)mg/dL, p = 0.008]. On NIRS/IVUS imaging analysis, the change in percent atheroma volume did not differ between the groups (−0.9 ± 0.25 vs. −0.2 ± 0.2%, p = 0.23). However, GLP-1RA treated patients demonstrated a greater frequency of maxLCBI_4mm regression (85.6 ± 0.1 vs. 42.0 ± 0.6%, p = 0.01). Multivariate analysis demonstrated that the GLP-1RA use was independently associated with maxLCBI_4mm regression (odds ratio = 4.41, 95%CI = 1.19–16.30, p = 0.02).

Conclusions

In statin-treated patients with T2D and CAD, GLP-1RAs produced favourable changes in lipidic plaque materials, consistent with its stabilization.

Background and aims

Guidelines recommend that high-risk patients with atherosclerotic cardiovascular disease (ASCVD) be treated with maximally tolerated statins to lower low-density lipoprotein cholesterol (LDL-C) levels and reduce the risk of major adverse cardiovascular events. In patients whose LDL-C remains elevated, non-statin adjunct therapies, including ezetimibe (EZE), bempedoic acid (BA), and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are recommended.

Methods

The impact of BA and EZE in a fixed-dose combination (FDC) on LDL-C goal attainment was evaluated using a simulation model developed for a United States cohort of high-risk adults with ASCVD. Treatment was simulated for 73,056 patients not at goal (LDL-C >70 mg/dL), comparing BA + EZE (FDC), EZE only, and no oral adjunct therapy (NOAT). The addition of PCSK9 inibitors was assumed after 1 year in patients not at LDL-C goal. Treatment efficacy was estimated from clinical trials. Patient-level outcomes were predicted over a 10-year horizon accounting for treatment discontinuation and general mortality.

Results

Baseline mean age of the cohort was 67 years, most were White (79%) and male (56%). A majority had established coronary artery disease (75%), 48% had diabetes, and mean LDL-C was 103.0 mg/dL. After 1 year, 79% of patients achieved LDL-C goal (mean, 61.1 mg/dL) with BA + EZE (FDC) compared to 58% and 42% with EZE (71.7 mg/dL) and NOAT (78.4 mg/dL), respectively.

Conclusions

This simulation shows that adding BA + EZE (FDC) to maximally tolerated statins would result in more patients achieving LDL-C goal than adding EZE alone or NOAT.

Background and aims

Hydroxychloroquine (HCQ) has a variable effect on cholesterol synthesis. To clarify this, we assessed the effect of HCQ on the cholesterol-synthesis pathway in individuals with low and high cholesterol absorption efficiency.

Method

A total of 53 acute myocardial infarction patients with a constant statin dose randomized to receive HCQ or placebo for six months in a double-blind manner, were classified further into low (n = 26) and high (n = 27) cholesterol absorbers based on the median baseline serum cholestanol level. Serum lipids and biomarkers of cholesterol synthesis (squalene, lanosterol, zymostenol, desmosterol, and lathosterol) and absorption efficiency (sitosterol and cholestanol), were measured at baseline and one-, six-, and 12-month follow-up visits.

Results

In low cholesterol absorbers, serum cholesterol concentration and cholesterol synthesis and absorption biomarkers did not differ between the HCQ and placebo groups. At one month, high cholesterol absorbers with HCQ had lower serum cholesterol concentration and serum lanosterol to cholesterol ratio in comparison to the placebo group (HCQ 3.18 ± 0.62 vs. placebo 3.71 ± 0.65, p = 0.042, and HCQ 10.4 ± 2.55 vs. placebo 13.1 ± 2.36, p = 0.008, respectively). At 12 months, serum desmosterol to cholesterol ratio was lower in HCQ users (HCQ 47.1 ± 7.08 vs. placebo 59.0 ± 13.1, p = 0.011).

Conclusions

HCQ affects the cholesterol-synthesis pathway in high cholesterol absorbers. It reduces serum lanosterol and desmosterol ratios and consequently serum cholesterol concentration possibly by inhibiting the activity of lanosterol synthase as described earlier in vitro studies.

Trial registration

ClinicalTrials.gov Identifier: NCT02648464.

Atherosclerotic cardiovascular disease (ASCVD) remains the main cause of death worldwide, and thus its prevention, early diagnosis and treatment is of paramount importance. Dyslipidemia represents a major ASCVD risk factor that should be adequately managed at different clinical settings. 2023 guidelines of the Hellenic Atherosclerosis Society focus on the assessment of ASCVD risk, laboratory evaluation of dyslipidemias, new and emerging lipid-lowering drugs, as well as diagnosis and treatment of lipid disorders in women, the elderly and in patients with familial hypercholesterolemia, acute coronary syndromes, heart failure, stroke, chronic kidney disease, diabetes, autoimmune diseases, and non-alcoholic fatty liver disease. Statin intolerance is also discussed.

Background and aims

To investigate the disparities in coronary collateral circulation (CCC) and peripheral serum metabolites among patients presenting with chronic total occlusion (CTO) of the coronary arteries, a non-targeted metabolic approach was employed.

Methods

A cohort of 22 patients diagnosed with CTO of coronary arteries in the context of coronary heart disease (CHD) was selected for blood sample collection from CCC and peripheral arteries. The patients were categorized into two groups, namely CTO-C and CTO-P. The Waters UPLC I-Class Plus is combined with the Q Exactive high-resolution mass spectrometer for metabolite separation and detection. The acquired raw data from mass spectrometry is subsequently imported into Compound Discoverer 3.2 software for comprehensive analysis, which seamlessly integrates the BGI Metabolome Database (BMDB), mzCloud database, and ChemSpider online database. Subsequently, the identified differential metabolites were subjected to a metabolic pathway enrichment analysis, as documented in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database.

Results

A total of 403 differential metabolites were identified in CCC and peripheral serum samples from patients with CTO of coronary arteries in CHD. Compared to the CTO-P group, the CTO-C group exhibited decreased levels of metabolites such as Testosterone, dehydroepiandrosterone (DHA), deoxyacetone, while demonstrating increased levels of metabolites including Progesterone, androstanone, l-threonine. The biosynthesis pathway of steroid hormones emerges as the key metabolic pathway significantly associated with differential metabolites.

Conclusions

Through metabolomics analysis, distinct differences in the CCC and peripheral serum metabolites have been identified among patients with CTO of coronary artery. Notably, a significant association between the steroid hormone biosynthesis pathway and CCC has been observed.

Background and aims

Previous studies have shown that lipoprotein apheresis can modify the plasma lipidome and pro-inflammatory and pro-thrombotic lipid mediators. This has not been examined for treatment with protein convertase subtilisin/kexin type 9 inhibitors such as evolocumab, which are increasingly used instead of lipoprotein apheresis in treatment-resistant familial hypercholesterolemia. The aim of this study was to compare the effects of evolocumab treatment and lipoprotein apheresis on the fatty acid profile and on formation of lipid mediators in blood samples.

Methods

We analyzed blood samples from 37 patients receiving either lipoprotein apheresis or evolocumab treatment as part of a previous study. Patients were stratified according to receiving lipoprotein apheresis (n = 19) and evolocumab treatment (n = 18). Serum fatty acid analysis was performed using gas chromatography flame ionization detection and plasma oxylipin analysis was done using liquid chromatography tandem mass spectrometry.

Results

Changing from lipoprotein apheresis to evolocumab treatment led to lower levels of omega-6 polyunsaturated fatty acid (n-6 PUFA) including arachidonic acid, dihomo-γ-linolenic acid and linoleic acid. Moreover, several n-6 PUFA-derived oxylipins were reduced after evolocumab treatment.

Conclusions

Given that arachidonic acid, either directly or as a precursor, is associated with the development of inflammation and atherosclerosis, evolocumab-mediated reductions of arachidonic acid and its metabolites might have an additional beneficial effect to lower cardiovascular risk.

Despite the improved efficacy of highly active antiretroviral therapy (HAART) in viral suppression, emerging evidence indicates an increased burden of noncommunicable diseases in people living with HIV (PLWH). Immune activation and persistently elevated levels of inflammation have been associated with endothelial dysfunction in PLWH, likely contributing to the development of cardiovascular diseases (CVDs). Here, electronic search databases including PubMed, Google Scholar, Cochrane Library, and Science Direct were used to retrieve scientific evidence reporting on any association between markers of endothelial function and CVD-related outcomes in PLWH on HAART. Extracted data was subjected to quality assessment using the Downs and Black checklist. Most (60 %) of the results indicated the presence of endothelial dysfunction in PLWH on HAART, and this was mainly through reduced flow mediated dilation and elevated serum makers of adhesion molecules like ICAM-1, VCAM-1, and P-selectin. The summarized evidence indicates an association between persistently elevated markers of endothelial dysfunction and a pro-inflammatory state in PLWH on HAART. Only a few studies reported on improved endothelial function markers in PLWH on HAART, while limited evidence is available to prove that endothelial dysfunction is associated with CVD-risk, which could be attributed to therapeutic effects of HAART. Limited studies with relatively high quality of evidence were included in this systematic review. In conclusion, results from this review lay an important foundation for future research, even a meta-analysis, that will improve the understanding of the contributing factors to the burden of CVDs in PLWH on HAART.