Atherosclerosis最新文献

Background: People with HIV (PWH) have a 2-fold increased risk of cardiovascular disease despite antiretroviral therapy (ART) and adjustment for traditional risk factors. Monocytes play a key role in early atherosclerotic events and have a 'pro-atherogenic' phenotype in PWH, as evidenced by an enhanced formation of lipid-laden foam cells ex vivo.

Methods: To elucidate the contributing mechanisms, we analysed the transcriptome of monocytes from virologically suppressed PWH who exhibited a high degree of foam cell formation ex vivo (HIV FC_High), and compared them to PWH and HIV-seronegative individuals with low monocyte atherogenic activity (HIV_FC Low and NEG, respectively, n = 10 per group, all male, median age 51 years [range 39-62]).

Results: Monocytes from HIV FC_High individuals exhibited substantial transcriptomic alterations including 3477 and 47 differentially expressed genes compared to the NEG and HIV FC_Low groups, respectively (adjusted p < 0.05). Genes significantly upregulated in HIV FC_High vs HIV FC_Low groups included those related to lipid synthesis (LIPI), cell structure/cytoskeleton and adhesion (XIRP1 and 2, LRFN5, CLDN4), extracellular matrix remodelling (FN1, PRELP, IGTA11), metalloproteinase activity (ADAMTS2, PAPPA) and members of the olfactory receptor family (OR52N1 and OR1L8). Gene set enrichment analysis identified 24 pathways significantly over-represented in monocytes from the HIV FC_High group compared with the HIV FC_Low group. These pathways included coagulation, fatty acid metabolism, glycolysis as well as TGFβ signalling and epithelial mesenchymal transition, together suggesting a fibrocyte-like phenotype.

Conclusions: Our findings indicate that monocytes from PWH without elevated traditional cardiovascular risk factors exhibit significant transcriptional changes which are associated with heightened atherosclerosis-promoting activity.

Background: It has been recognized that hypertriglyceridemia (HTG) is associated with kidney damage. Monogenic and polygenic causes of extreme HTG characterized by severe chylomicronemia (TG > 885 mg/dl or 10 mmol/L) constitute unique models to investigate the potential nephrotoxic effects of sustained and severe exposure to HTG.

Methods: This study had two components: (1) kidney biopsies of three patients with severe chylomicronemia and proteinuria were analyzed; (2) a cross-sectional review of the medical files of two independent cohorts of patients with the Familial Chylomicronemia Syndrome (FCS) or Multifactorial Chylomicronemia Syndrome (MCS) followed in Italy and Canada was performed. Renal involvement was defined by the presence of proteinuria, reduced eGFR (<90 mL/min/1.73 m²), or hyperfiltration (≥105 mL/min/1.73 m²).

Results: Histological findings in the three patients with severe chylomicronemia revealed diverse patterns of glomerular injury, including lipid-laden glomerular damage, foam-cell infiltration, all consistent with lipid-associated nephropathy. Among the 84 adults with severe chylomicronemia (38 F CS, 46 MCS), 35 % had a history of proteinuria, 49 % presented eGFR<90 mL/min/1.73 m², 8 % had eGFR<60 mL/min/1.73 m², and 41 % showed hyperfiltration. Hypertension and diabetes emerged as independent covariates for proteinuria and reduced eGFR.

Conclusions: These data suggest that severe chylomicronemia due to FCS and MCS is predominantly associated with proteinuria, which might be the possible consequences of lipid-laden glomerular injury. Therefore, renal disease should be included in the list of possible complications of severe chylomicronemia, thus suggesting that renal monitoring have to be considered as part of clinical management of these conditions.

Background and aims: Despite a coronary artery calcification (CAC) score of zero, 5-6 % of middle-aged individuals still exhibit underlying atherosclerosis. This cross-sectional study aimed first to investigate the association between estimated cardiorespiratory fitness (CRF) and atherosclerosis in individuals with zero CAC, second to assess whether adding CRF to the Systematic Coronary Risk Evaluation (SCORE) model improves the explained variance in atherosclerosis, and third to characterise the association across CRF levels.

Methods: We included 2322 middle-aged individuals with zero CAC from the Swedish CArdioPulmonary bioImage Study (SCAPIS). CRF was estimated as maximal oxygen consumption (ml·kg^-1·min^-1) using submaximal cycle testing, CAC was assessed by non-contrast computed tomography, and atherosclerosis by coronary computed tomography angiography. Logistic regression and Chi-squared tests analysed associations and compared prevalences across CRF groups.

Results: One ml·kg^-1·min^-1 higher CRF was associated with 4.5 % lower odds of atherosclerosis (p < 0.01), while one percentage point higher SCORE corresponded to 47.4 % higher odds (p < 0.01). The combined CRF-SCORE model explained significantly more variance in atherosclerosis than SCORE alone (p < 0.01). When categorised as "low" and "high", atherosclerosis prevalence was 104 % higher in low-CRF men (p < 0.01) and 127 % higher in low-CRF women (p < 0.001) compared to high-CRF counterparts.

Conclusions: In individuals with zero CAC, low CRF was associated with more than double the prevalence of atherosclerosis compared to high CRF. Adding CRF to SCORE explained a greater proportion of variance in atherosclerosis. These findings suggest that CRF could help identify individuals at elevated risk, beyond traditional assessments.

Background: Diabetes mellitus, smoking, hypertension, and hyperlipidemia are well-studied cardiovascular risk factors (CVRF) for coronary artery disease (CAD). However, their combined and individual influence on atherosclerotic total plaque volume (TPV) and plaque subtypes as assessed by coronary computed tomographic angiography (CCTA) has not been well evaluated.

Purpose: To evaluate the association between CVRF on TPV and plaque subtypes and to develop quantitative plaque nomograms stratified by sex, age, and CVRF using CCTA findings.

Methods: This analysis included participants from the ADVANCE (Assessing Diagnostic Value of Noninvasive CT-FFR in Coronary Care) registry. Quantitative assessment of TPV and plaque subtypes was performed using an Artificial Intelligence-Enabled Quantitative Coronary Plaque Analysis tool.

Results: A total of 4430 patients were included in the analysis, with a median age of 67.0 [59.0-73.0] years, and 1512 (34.1 %) were women. The median TPV was 390 mm³ (IQR: 163-760 mm³) and it was significantly higher in male participants (460 mm³; IQR 197-855 mm³) compared to female participants (280.5 mm³; IQR: 118-583 mm³) (P < 0.0001). Independent of sex, participants with CVRF had higher median TPVs (404.5 mm³; IQR: 175-788.5 mm³) than those without CVRF (187 mm³; IQR: 74-431 mm³) (P < 0.0001). On ROC analysis, age emerged as the strongest predictor of TPV >250 mm³ (AUC 0.62; CI: 0.60-0.64), with only modest improvements in the model after adding male sex (0.67; CI: 0.65-0.69) and CVRF (0.69; CI: 0.68-0.71).

Conclusions: Our data indicate that TPV is significantly higher in participants with CVRF compared to those without. Age demonstrated the strongest association with plaque volume, while the addition of CVRF only modestly increased the AUC. Altogether, age and CVRF were only modestly associated with plaque volume, highlighting the need for further research to fully understand the potential and limitations of plaque imaging assessing the extent and severity of CAD, in patients with and without CVRF.

Background and aims: Calcified plaques have traditionally been regarded as advanced and quiescent atheroma. However, pathological studies indicate lipid content within calcified plaques, suggesting that calcified plaques may harbor active lipidic contents. This study evaluated lipidic plaque content in calcified lesions in vivo using IVUS, OCT and near-infrared spectroscopy (NIRS).

Methods: We analyzed 325 cross-sectional frames at 65 calcified lesions in 58 CAD patients from the REASSURE-NIRS registry (NCT04864171). OCT-derived calcification measures, and the arc of NIRS-derived yellow signals within calcification (YSC) were measured. Plaque features were compared between cross-sectional frames with YSC arc < and ≥63° (=median).

Results: The median calcification arc was 224° (statin = 78 %, LDL-C = 81.5 mg/dL), and 73.8 % of images exhibited calcification arc ≥180°. Any YSC was observed at 84.3 % of analyzed frames. YSC arc ≥63° was associated with thinner (743 ± 276 vs. 882 ± 247 μm, p < 0.001) and deeper calcification (median:50 vs. 30 μm, p = 0.002), whereas the frequency of macrophage (16.6 % vs. 11.7 %, p = 0.265), microvessels (0.6 % vs. 0.6 %, p = 1.000) and cholesterol crystals (1.2 % vs. 0.0 %, p = 0.498) did not differ between two groups. Multivariate analysis identified calcification thickness (β = -0.446, 95 % CI = -0.661-0.231, p < 0.001) as an independent predictor of YSC arc ≥63°, whereas calcification arc (β = 0.000, 95 % CI = -0.001-0.001, p = 0.788) and depth (β = -0.592, 95 % CI = -1.408-0.224, p = 0.155) were not. Notably, LDL-C<55 mg/dL was associated with larger calcification arc (p < 0.001), but the YSC arc was not necessarily smaller despite achieving LDL-C<55 mg/dL (p = 0.671).

Conclusion: Lipidic contents existed at calcified lesions exhibiting thinner calcification. This lipidic feature at calcified lesions less likely undergo changes in response to LDL-C<55 mg/dL.