Atherosclerosis最新文献

Background and aims: Histologic studies indicated that healed plaque, characterized by a multilayered pattern, is indicative of prior atherothrombosis and subsequent healing. However, longitudinal in vivo data on healed plaque formation in non-culprit plaques are limited. This study aimed to investigate serial changes and clinical significance of new layered pattern formation in non-culprit plaques in patients with acute coronary syndromes (ACS) using serial optical coherence tomography (OCT) imaging.

Methods: ACS patients who underwent two OCTs at baseline and 1-year follow-up were included. Serial changes in morphologic characteristics of non-culprit plaques were evaluated. New layered pattern was defined as a new signal-rich layer on the plaque surface at follow-up that was not present at baseline.

Results: Among 553 non-culprit plaques observed in 222 patients, 82 (14.8 %) exhibited a new layered pattern at follow-up. Thin-cap fibroatheroma, macrophage, and thrombus were identified as independent predictors of the new layered pattern. Plaques with new layered pattern formation showed a greater significant reduction in luminal area and lipid content, as well as a greater increase in fibrous cap thickness compared to those without. The incidence of 6-year non-culprit-related major adverse cardiac events was higher in patients with new layered pattern than in those without (25.4 % vs. 10.8 %, p = 0.011), mainly due to clinically driven coronary revascularization.

Conclusions: Plaque destabilization and subsequent healing frequently occur in non-culprit plaques after ACS. The formation of a new layered pattern may contribute to temporary plaque stabilization, but results in luminal stenosis and worse clinical outcomes.

Background and aims: Recent reports have shown that subjects with high high-density lipoprotein cholesterol (HDLc) levels are paradoxically at increased risk for all-cause and cardiovascular mortality. The aim was to study the association of HDLc concentration with mortality in subjects with high cholesterol.

Methods: We analyzed total mortality, cardiovascular mortality, and non-cardiovascular mortality in a cohort of 2992 subjects with primary hypercholesterolemia, who were followed for 10.2 years (range 1-25 years), with a total of 30,602 subject-years of follow-up.

Results: During follow-up, 168 subjects died, with 52 (13.7 %), 105 (4.80 %), and 11 (2.60 %) in the low, normal, and high HDLc groups, respectively (p < 0.001). The risk of death was 2.89 times higher (95 % confidence interval (CI), 1.50-5.57, p < 0.001) in subjects in the low HDLc group compared to those in the high HDLc group and 1.48 times higher (95 % CI 0.80-2.76, p = 0.214) in the normal HDLc group compared to the high HDLc group. However, HDLc concentration and HDLc groups based on HDLc concentration were not independently associated with mortality in Cox regression analysis. Cardiovascular and non-cardiovascular mortalities showed similar results.

Conclusions: All types of mortality were lower in subjects with primary hypercholesterolemia and with high HDLc in univariate analysis. Elevated HDLc was not associated with total, cardiovascular, and non-cardiovascular mortality when adjusted for major cardiovascular risk factors.

Background and aims: Statin-associated muscle symptoms (SAMS) are a major cause of treatment discontinuation. Clinical Pharmacogenetics Implementation Consortium (CPIC) recommend dose adjustment for statin treatment according to known SLCO1B1 genotype to reduce SAMS. We hypothesized that the association between SLCO1B1 genotype and SAMS is misestimated because of publication bias.

Methods: We searched published systematic reviews on the association between SLCO1B1 genotype and SAMS. To assessed publication bias, we used funnel plot visual inspection, Egger's test, and the Bayes Factor (BF_{Publication-bias}) from Robust Bayesian Meta-Analysis (RoBMA). We compared the odds ratios (OR_Uncorrected) from meta-analyses before and after correcting for publication bias using trim-and-fill (OR_Trim&Fill) and RoBMA (OR_RoBMA) methods.

Results: We included 8 cohort and 11 case-control studies, totaling 62 OR of three SLCO1B1 genotypes and six statin drugs. In the primary analysis, the funnel plot was suggestive of publication bias, confirmed by Egger's test (p=0.001) and RoBMA (BF_{Publication-bias} = 18). Correcting the estimate for publication bias resulted in loss of the association, from a significant OR_Uncorrected (1.31 95%CI [1.13-1.53]) to corrected ORs suggesting no difference: OR_Trim&Fill (1.07 95%CI [0.89-1.30]) and OR_RoBMA (1.02 95%CI [1.00-1.33]). This suggested that publication bias overestimated the association by 18 % and 23 %, respectively. Similar results were found for genotype rs4149056, simvastatin and atorvastatin.

Conclusions: The effect of the SLCO1B1 genotype on the risk of developing SAMS is overestimated in the published literature, especially rs4149056. This could lead prescribers to incorrectly decreasing statin doses or even avoiding statin use, leading to a loss of the potential cardiovascular benefit of statins.

Background and aims: Environmental and genetic factors predispose to cardiovascular disease. Some first-generation immigrants have a higher cardiovascular risk in Sweden, while less is known about second-generation immigrants. We aimed to analyze the risk of acute myocardial infarction (AMI) among second-generation immigrants in Sweden.

Methods: We included all individuals 18 years of age and older in Sweden, n = 4,580,967. AMI was defined as at least one registered diagnosis in the National Patient Register between January 1, 1998, and December 31, 2018. Cox regression analysis was used to estimate the relative risk (hazard ratio = HR) with 99 % confidence interval (CI) of incident AMI with adjustments made for age, sociodemographics, and comorbidities, and also subdivided into two age groups, i.e., 18-54 years and ≥55 years.

Results: A total of 158,815 AMI events were registered. Fully adjusted models showed HRs (99 % CI) in second-generation immigrants for men 1.05 (1.01-1.08), and for women 0.99 (0.94-1.05). A marginally higher MI risk was found only among men with parents from the Nordic countries in the fully adjusted model, HR 1.05 (1.01-1.10), and a lower risk only among women with parents from Asian countries, HR 0.47 (0.30-0.75). No significant overall differences in AMI risk were seen in older and younger second-generation immigrants.

Conclusions: The overall risk of AMI was similar for most groups of men and women with foreign-born parents compared to native-born Swedes. Our findings suggest that environmental factors may be more important than genetic factors, but further studies are needed to quantify these risks concerning AMI.

Background and aims: The significance of left ventricular mass and chamber volumes from non-contrast computed tomography (CT) for predicting major adverse cardiovascular events (MACE) has not been studied. Our objective was to evaluate the role of artificial intelligence-enabled multi-chamber cardiac volumetry from non-contrast CT for long-term risk stratification in asymptomatic subjects without known coronary artery disease.

Methods: Our study included 2022 asymptomatic individuals (55.6 ± 9.0 years; 59.2 % male) from the EISNER (Early Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) trial. Multi-chamber cardiac volumetry was performed using deep-learning algorithms from routine non-contrast CT scans for coronary artery calcium scoring. MACE was defined as cardiac death, acute coronary syndrome, and late (>180 days) revascularization.

Results: A total of 215 individuals (11 %) suffered MACE at a mean follow-up of 13.9 ± 3 years. Individuals with MACE had higher left ventricular mass (115.1g vs. 105.2g, p < 0.001). In a multivariable analysis adjusted for cardiovascular risk factors and medications, left ventricular mass (HR 2.76, p<0.001) and coronary artery calcium score (HR 1.34, p<0.001) were independent predictors of long-term MACE. Adding left ventricular mass to the coronary calcium score improved the Receiver Operating Characteristic Area Under the Curve (AUC 0.753 vs 0.767, p=0.031) with continuous net reclassification index of 18 % (p=0.011). Left ventricular mass (HR 3.89, p<0.001), but not the coronary artery calcium score predicted cardiovascular death.

Conclusions: Left ventricular mass quantified automatically by AI from routine non-contrast CT independently predicted long-term MACE over and above the coronary calcium score in asymptomatic participants without known coronary artery disease.