Microplastics and Nanoplastics in Atheromas and Cardiovascular Events.

BACKGROUND: Microplastics and nanoplastics (MNPs) are emerging as a potential risk factor for cardiovascular disease in preclinical studies. Direct evidence that this risk extends to humans is lacking. METHODS: We conducted a prospective, multicenter, observational study involving patients who were undergoing carotid endarterectomy for asymptomatic carotid artery disease. The excised carotid plaque specimens were analyzed for the presence of MNPs with the use of pyrolysis-gas chromatography-mass spectrometry, stable isotope analysis, and electron microscopy. Inflammatory biomarkers were assessed with enzyme-linked immunosorbent assay and immunohistochemical assay. The primary end point was a composite of myocardial infarction, stroke, or death from any cause among patients who had evidence of MNPs in plaque as compared with patients with plaque that showed no evidence of MNPs. RESULTS: A total of 304 patients were enrolled in the study, and 257 completed a mean (±SD) follow-up of 33.7±6.9 months. Polyethylene was detected in carotid artery plaque of 150 patients (58.4%), with a mean level of 21.7±24.5 µg per milligram of plaque; 31 patients (12.1%) also had measurable amounts of polyvinyl chloride, with a mean level of 5.2±2.4 µg per milligram of plaque. Electron microscopy revealed visible, jagged-edged foreign particles among plaque macrophages and scattered in the external debris. Radiographic examination showed that some of these particles included chlorine. Patients in whom MNPs were detected within the atheroma were at higher risk for a primary end-point event than those in whom these substances were not detected (hazard ratio, 4.53; 95% confidence interval, 2.00 to 10.27; P<0.001). CONCLUSIONS: In this study, patients with carotid artery plaque in which MNPs were detected had a higher risk of a composite of myocardial infarction, stroke, or death from any cause at 34 months of follow-up than those in whom MNPs were not detected. (Funded by Programmi di Ricerca Scientifica di Rilevante Interesse Nazionale and others; ClinicalTrials.gov number, NCT05900947.).

Exercise and Coronary Atherosclerosis: Observations, Explanations, Relevance, and Clinical Management.

Physical activity and exercise training are effective strategies for reducing the risk of cardiovascular events, but multiple studies have reported an increased prevalence of coronary atherosclerosis, usually measured as coronary artery calcification, among athletes who are middle-aged and older. Our review of the medical literature demonstrates that the prevalence of coronary artery calcification and atherosclerotic plaques, which are strong predictors for future cardiovascular morbidity and mortality, was higher in athletes compared with controls, and was higher in the most active athletes compared with less active athletes. However, analysis of plaque morphology revealed fewer mixed plaques and more often only calcified plaques among athletes, suggesting a more benign composition of atherosclerotic plaques. This review describes the effects of physical activity and exercise training on coronary atherosclerosis in athletes who are middle-aged and older and aims to contribute to the understanding of the potential adverse effects of the highest doses of exercise training on the coronary arteries. For this purpose, we will review the association between exercise and coronary atherosclerosis measured using computed tomography, discuss the potential underlying mechanisms for exercise-induced coronary atherosclerosis, determine the clinical relevance of coronary atherosclerosis in middle-aged athletes and describe strategies for the clinical management of athletes with coronary atherosclerosis to guide physicians in clinical decision making and treatment of athletes with elevated coronary artery calcification scores.

The novel collagen matrikine, endotrophin, is associated with mortality and cardiovascular events in patients with atherosclerosis.

BACKGROUND: Rupture of atherosclerotic plaques is the major cause of acute cardiovascular events. The biomarker PRO-C6 measuring Endotrophin, a matrikine of collagen type VI, may provide valuable information detecting subjects in need of intensified strategies for secondary prevention. OBJECTIVE: In this study, we evaluate endotrophin in human atherosclerotic plaques and circulating levels of PRO-C6 in patients with atherosclerosis, to determine the predictive potential of the biomarker. METHODS: Sections from the stenotic human carotid plaques were stained with the PRO-C6 antibody. PRO-C6 was measured in serum of patients enrolled in the Carotid Plaque Imagining Project (CPIP) (discovery cohort, n = 577) and the innovative medicines initiative surrogate markers for micro- and macrovascular hard end-points for innovative diabetes tools (IMI-SUMMIT, validation cohort, n = 1,378). Median follow-up was 43 months. Kaplan-Meier curves and log-rank tests were performed in the discovery cohort. Cox proportional hazard regression analysis (HR with 95% CI) was used in the discovery cohort and binary logistic regression (OR with 95% CI) in the validation cohort. RESULTS: PRO-C6 was localized in the core and shoulder of the atherosclerotic plaque. In the discovery cohort, PRO-C6 independently predicted future cardiovascular events (HR 1.089 [95% CI 1.019 -1.164], p = 0.01), cardiovascular death (HR 1.118 [95% CI 1.008 -1.241], p = 0.04) and all-cause death (HR 1.087 [95% CI 1.008 -1.172], p = 0.03). In the validation cohort, PRO-C6 predicted future cardiovascular events (OR 1.063 [95% CI 1.011 -1.117], p = 0.017). CONCLUSION: PRO-C6 is present in the atherosclerotic plaque and associated with future cardiovascular events, cardiovascular death and all-cause mortality in two large prospective cohorts.

Sex Differences in Coronary Artery Calcium and Long-term CV Mortality.

PURPOSE OF REVIEW: To summarize differences in plaque depositions, coronary artery calcium (CAC) scoring, and the role of CAC in predicting atherosclerotic cardiovascular disease (ASCVD) mortality in men and women. RECENT FINDINGS: Women have coronary plaque that is more lipid-rich, dense, and less calcified than their male counterparts. CAC scoring has emerged as a useful tool to quantify ASCVD burden. However, recent evidence favors the use of sex-adjusted CAC cutoffs for women to account for the relatively lower overall CAC burden and therefore risk stratify women appropriately. Several studies have identified CAC distribution patterns in women associated with increased CV mortality, particularly the number of lesions involved, CAC volume, and size. Multiple studies have shown that the pathophysiology and associated risks of ASCVD are different in women when compared with men. CAC scoring is a tool that is widely being used for ASCVD risk stratification. Recent studies have shown that although men have higher CAC burdens, women are more likely to develop plaque erosions with non-calcified plaque that carries a greater risk for cardiovascular events. Providers should be aware of sex-specific CAC patterns carrying increased mortality risk for women, particularly increasing lesion size and number. Given the differences in plaque composition and distribution, revised sex-adjusted CAC scoring is suggested to better risk stratify patients, especially those deemed intermediate risk, and decrease CV mortality.

Mortality following myocardial infarction among HIV-infected persons: the Center for AIDS Research Network Of Integrated Clinical Systems (CNICS).

BACKGROUND: Persons with human immunodeficiency virus (HIV) have higher risks for myocardial infarction (MI) than the general population. This is driven in part by higher type 2 MI (T2MI, due to coronary supply-demand mismatch) rates among persons with HIV (PWH). In the general population, T2MI has higher mortality than type 1 MI (T1MI, spontaneous and generally due to plaque rupture and thrombosis). PWH have a greater burden of comorbidities and may therefore have an even greater excess risk for complication and death in the setting of T2MI. However, mortality patterns after T1MI and T2MI in HIV are unknown. METHODS: We analyzed mortality after MI among PWH enrolled in the multicenter, US-based Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort (N = 28,186). Incident MIs occurring between January 1, 1996, and December 31, 2014, were centrally adjudicated and classified as T1MI or T2MI. We first compared mortality following T1MI vs. T2MI among PWH. Cox survival analyses and Bayesian model averaging were then used to evaluate pre-MI covariates associated with mortality following T1MI and T2MI. RESULTS: Among the 596 out of 28,186 PWH who experienced MI (2.1%; 293 T1MI and 303 T2MI), mortality rates were significantly greater after T2MI (22.2/100 person-years; 1-, 3-, and 5-year mortality 39%, 52%, and 62%) than T1MI (8.2/100 person-years; 1-, 3-, and 5-year mortality 15%, 22%, and 30%). Significant mortality predictors after T1MI were higher HIV viral load, renal dysfunction, and older age. Significant predictors of mortality after T2MI were low body-mass index (BMI) and detectable HIV viral load. CONCLUSIONS: Mortality is high following MI for PWH and substantially greater after T2MI than T1MI. Predictors of death after MI differed by type of MI, reinforcing the different clinical scenarios associated with each MI type and the importance of considering MI types separately.

Accelerated coronary atherosclerosis not explained by traditional risk factors in 13% of young individuals.

IMPORTANCE: Most individuals who die of sudden cardiac death (SCD) display very advanced lesions of atherosclerosis in their coronary arteries. Thus, we sought to identify and characterize a putative subpopulation of young individuals exhibiting accelerated coronary artery atherosclerosis. OBJECTIVE: Our analysis of the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study-which examined 2651 individuals, obtaining quantitative measurements of traditional risk factors for coronary heart disease (CHD)-aimed to identify individuals with advanced coronary artery lesions, and to determine whether risk factors could account for such rapid disease progression, or not. DESIGN: Using the cross-sectional PDAY study data, an exploratory de facto analysis stratified the population by age and observed number of coronary raised lesions and examined these groups via Poisson regression modeling. A separate de novo approach utilized Poisson mixture modeling to generate low- and high-growth groups based on measurements of traditional risk factors, and identified factors contributing to disease progression. PARTICIPANTS: Participants, n = 2651 individuals aged 15-34, who had died of non-cardiac death, were recruited post mortem. Tissues and other samples were harvested for analysis (details in previously published PDAY studies). Main Outcome(s) and Measure(s). Using quantitative measurements of raised coronary lesions and traditional risk factors of CHD, we sought to identify which risk factors account for disease progression. RESULTS: A group of ~13% of the PDAY population exhibits accelerated coronary atherosclerosis despite their young age. Several traditional risk factors were associated with increased odds of inclusion in this subgroup, reflecting current understanding of these markers of disease. However, only age was a significant contributing factor to the observed coronary lesion burden. CONCLUSIONS: While a range of traditional risk factors contribute to an individual's inclusion to the identified subgroup with accelerated atherosclerosis, these factors, with the exceptions of age, are not able to predict an individual's lesion burden. Moreover, unattributed variances in observations indicate the need to study novel risk factors. SHORT SUMMARY: Hypothesis The extent of coronary atherosclerotic disease is limited and homogeneous within youth, and its progression can be accounted for by traditional risk factors in this population. FINDINGS: A subpopulation (~13%) of the Pathobiological Determinants of Atherosclerosis in Youth cohort exhibited accelerated coronary artery atherosclerosis. While several traditional risk factors contribute to an individual's inclusion in this subgroup, these factors, with the exceptions of age, do not predict accurately an individual's lesions burden. Critically, unattributed variances in observations indicate the need for the identification of novel risk factors. MEANING: Screening of the general population at a young age for high-risk group membership could provide opportunity for disease prevention and avoidance of the worse complications such as myocardial infarction and sudden cardiac death later in life.

Impact of Accumulated Serum Uric Acid on Coronary Culprit Lesion Morphology Determined by Optical Coherence Tomography and Cardiac Outcomes in Patients with Acute Coronary Syndrome.

OBJECTIVES: We aimed to examine the relations of very high levels of serum uric acid (sUA) with features of culprit lesion plaque morphology determined by optical coherence tomography (OCT) and adverse clinical outcomes in patients with acute coronary syndrome (ACS). METHODS: We retrospectively compared ACS patients according to sUA levels of > 8.0 mg/dL (n = 169), 7.1-8.0 mg/dL (n = 163), 6.1-7.0 mg/dL (n = 259), and ≤6.0 mg/dL (n = 717). Angiography and OCT findings were analyzed in patients with preintervention OCT and the 4 sUA groups (> 8.0 mg/dL, n = 61; 7.1-8.0 mg/dL, n = 72; 6.1-7.0 mg/dL, n = 131; and ≤6.0 mg/dL, n = 348) were compared. RESULTS: Cardiogenic shock was more prevalent in ACS patients with sUA > 8.0 mg/dL (22% vs. 19% vs. 10% vs. 6%, p < 0.001). Plaque rupture was observed more prevalently by OCT in patients with sUA > 8.0 mg/dL (67% vs. 47% vs. 56% vs. 45%, p = 0.027). At the 2-year follow-up, Kaplan-Meier estimates showed higher cardiac mortality in patients with sUA > 8.0 mg/dL (25% vs. 12% vs. 5% vs. 5%, p < 0.001). After adjusting for traditional cardiovascular risk factors and creatinine levels, patients with sUA > 8.0 mg/dL showed a 4.5-fold increased risk in 2-year cardiac death by multivariate Cox proportional hazard analysis (hazard ratio 4.54, 95% confidence interval 2.98-6.91; p < 0.001). CONCLUSIONS: Very high sUA levels like > 8.0 mg/dL are the primary predictor of 2-year cardiac mortality and could partly be caused by adverse effects of accumulated sUA on plaque morphology in patients with ACS.

Echocardiographic Risk Factors for Stroke and Outcomes in Patients With Atrial Fibrillation Anticoagulated With Apixaban or Warfarin.

BACKGROUND AND PURPOSE: Few data exist on the long-term outcomes of patients with spontaneous echo contrast (SEC), left atrial/left atrial appendage (LA/LAA) thrombus, and complex aortic plaque (CAP), in patients with atrial fibrillation receiving oral anticoagulation. We explored the relationship between these 3 echocardiographic findings and clinical outcomes, and the comparative efficacy and safety of apixaban and warfarin for each finding. METHODS: Patients from the ARISTOTLE trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) with SEC, LA/LAA thrombus, or CAP diagnosed by either transthoracic or transesophageal echocardiography were compared with patients with none of these findings on transesophageal echocardiography. RESULTS: A total of 1251 patients were included: 217 had SEC, 127 had LA/LAA thrombus, 241 had CAP, and 746 had none. The rates of stroke/systemic embolism were not significantly different among patients with and without these echocardiographic findings (hazard ratio, 0.96; 95% confidence interval, 0.25-3.60 for SEC; hazard ratio, 1.27; 95% confidence interval, 0.23-6.86 for LA/LAA thrombus; hazard ratio, 2.21; 95% confidence interval, 0.71-6.85 for CAP). Rates of ischemic stroke, myocardial infarction, cardiovascular death, and all-cause death were also not different between patients with and without these findings. For patients with either SEC or CAP, there was no evidence of a differential effect of apixaban over warfarin. For patients with LA/LAA thrombus, there was also no significant interaction, with the exception of all-cause death and any bleeding where there was a greater benefit of apixaban compared with warfarin among patients with no LA/LAA thrombus. CONCLUSIONS: In anticoagulated patients with atrial fibrillation and risk factors for stroke, echocardiographic findings do not seem to add to the risk of thromboembolic events. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984.

Plaque rupture and intact fibrous cap assessed by optical coherence tomography portend different outcomes in patients with acute coronary syndrome.

AIMS: Patients presenting with acute coronary syndrome (ACS) may have different plaque morphologies at the culprit lesion. In particular, plaque rupture (PR) has been shown as the more frequent culprit plaque morphology in ACS. However, its prognostic value is still unknown. In this study, we evaluated the prognostic value of PR, compared with intact fibrous cap (IFC), in patients with ACS. METHODS AND RESULTS: We enrolled consecutive patients admitted to our Coronary Care Unit for ACS and undergoing coronary angiography followed by interpretable optical coherence tomography (OCT) imaging. Culprit lesion was classified as PR and IFC by OCT criteria. Prognosis was assessed according to such culprit lesion classification. Major adverse cardiac events (MACEs) were defined as the composite of cardiac death, non-fatal myocardial infarction, unstable angina, and target lesion revascularization (follow-up mean time 31.58 ± 4.69 months). The study comprised 139 consecutive ACS patients (mean age 64.3 ± 12.0 years, male 73.4%, 92 patients with non-ST elevation ACS and 47 with ST-elevation ACS). Plaque rupture was detected in 82/139 (59%) patients. There were no differences in clinical, angiographic, or procedural data between patients with PR when compared with those having IFC. Major adverse cardiac events occurred more frequently in patients with PR when compared with those having IFC (39.0 vs. 14.0%, P = 0.001). Plaque rupture was an independent predictor of outcome at multivariable analysis (odds ratio 3.735, confidence interval 1.358-9.735). CONCLUSION: Patients with ACS presenting with PR as culprit lesion by OCT have a worse prognosis compared with that of patients with IFC. This finding should be taken into account in risk stratification and management of patients with ACS.

Systemic Glucocorticoids Are Associated With Mortality After Carotid Endarterectomy.

Glucocorticoids (GCs) are widely used anti-inflammatory drugs well known to cause many adverse effects. Still, there is a dearth of data on the long-term cardiovascular effects of GCs in patients with established cardiovascular disease and the effect on atherosclerotic plaque composition. A total of 1894 patients who underwent carotid endarterectomy (CEA), of whom 40 patients received systemic GCs, were included in the Athero-Express Biobank. Atherosclerotic plaque samples and peripheral blood samples were obtained during CEA. Cardiovascular events during 3 years of follow-up were investigated using Cox regression modeling to adjust for possible confounding. Atherosclerotic plaque composition was examined using immunohistochemical staining. Use of GCs at inclusion was associated with markedly increased incidences of ischemic stroke (15.2% vs. 5.9%), composite events (48.5% vs. 26.9%), and cardiovascular death (21.2% vs. 5.7%), as well as an increased risk of cardiovascular death (hazards ratio 2.7, 95% confidence interval, 1.1-6.7) and all-cause death (hazards ratio 2.3, 95% confidence interval, 1.1-4.8) after 2.6 years of follow-up. None of the histological features of atherosclerotic plaques were significantly different in patients using GCs. After CEA, the use of systemic GCs is independently associated with an increased incidence of cardiovascular events and an increased risk of cardiovascular and all-cause death, but not atherosclerotic plaque composition.

Induction of C-X-C chemokine receptor type 7 (CXCR7) switches stromal cell-derived factor-1 (SDF-1) signaling and phagocytic activity in macrophages linked to atherosclerosis.

The discovery of CXCR7 as a new receptor for SDF-1 places many previously described SDF-1 functions attributed to CXCR4 in question, though whether CXCR7 acts as a signaling or "decoy" receptor has been in debate. It is known that CXCR7 is not expressed in normal blood leukocytes; however, the potential role of leukocyte CXCR7 in disease states has not been addressed. The aim of this study was to determine the expression and function of macrophage CXCR7 linked to atherosclerosis. Here, we show that CXCR7 was detected in macrophage-positive area of aortic atheroma of ApoE-null mice, but not in healthy aorta. During monocyte differentiation to macrophages, CXCR7 was up-regulated at mRNA and protein levels, with more expression in M1 than in M2 phenotype. In addition, CXCR7 induction was associated with a SDF-1 signaling switch from the pro-survival ERK and AKT pathways in monocytes to the pro-inflammatory JNK and p38 pathways in macrophages. The latter effect was mimicked by a CXCR7-selective agonist TC14012 and abolished by siRNA knockdown of CXCR7. Furthermore, CXCR7 activation increased macrophage phagocytic activity, which was suppressed by CXCR7 siRNA silencing or by inhibiting either the JNK or p38 pathways, but was not affected by blocking CXCR4. Finally, activation of CXCR7 by I-TAC showed a similar signaling and phagocytic activity in macrophages with no detectable CXCR3. We conclude that CXCR7 is induced during monocyte-to-macrophage differentiation, which is required for SDF-1 and I-TAC signaling to JNK and p38 pathways, leading to enhanced macrophage phagocytosis, thus possibly contributing to atherogenesis.

Clopidogrel plus aspirin versus warfarin in patients with stroke and aortic arch plaques.

BACKGROUND AND PURPOSE: Severe atherosclerosis in the aortic arch is associated with a high risk of recurrent vascular events, but the optimal antithrombotic strategy is unclear. METHODS: This prospective randomized controlled, open-labeled trial, with blinded end point evaluation (PROBE design) tested superiority of aspirin 75 to 150 mg/d plus clopidogrel 75 mg/d (A+C) over warfarin therapy (international normalized ratio 2-3) in patients with ischemic stroke, transient ischemic attack, or peripheral embolism with plaque in the thoracic aorta>4 mm and no other identified embolic source. The primary end point included cerebral infarction, myocardial infarction, peripheral embolism, vascular death, or intracranial hemorrhage. Follow-up visits occurred at 1 month and then every 4 months post randomization. RESULTS: The trial was stopped after 349 patients were randomized during a period of 8 years and 3 months. After a median follow-up of 3.4 years, the primary end point occurred in 7.6% (13/172) and 11.3% (20/177) of patients on A+C and on warfarin, respectively (log-rank, P=0.2). The adjusted hazard ratio was 0.76 (95% confidence interval, 0.36-1.61; P=0.5). Major hemorrhages including intracranial hemorrhages occurred in 4 and 6 patients in the A+C and warfarin groups, respectively. Vascular deaths occurred in 0 patients in A+C arm compared with 6 (3.4%) patients in the warfarin arm (log-rank, P=0.013). Time in therapeutic range (67% of the time for international normalized ratio 2-3) analysis by tertiles showed no significant differences across groups. CONCLUSIONS: Because of lack of power, this trial was inconclusive and results should be taken as hypothesis generating. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00235248.

Prediction of mortality using a multi-bed vascular calcification score in the Diabetes Heart Study.

BACKGROUND: Vascular calcified plaque, a measure of subclinical cardiovascular disease (CVD), is unlikely to be limited to a single vascular bed in patients with multiple risk factors. Consideration of vascular calcified plaque as a global phenomenon may allow for a more accurate assessment of the CVD burden. The aim of this study was to examine the utility of a combined vascular calcified plaque score in the prediction of mortality. METHODS: Vascular calcified plaque scores from the coronary, carotid, and abdominal aortic vascular beds and a derived multi-bed score were examined for associations with all-cause and CVD-mortality in 699 European-American type 2 diabetes (T2D) affected individuals from the Diabetes Heart Study. The ability of calcified plaque to improve prediction beyond Framingham risk factors was assessed. RESULTS: Over 8.4 ± 2.3 years (mean ± standard deviation) of follow-up, 156 (22.3%) participants were deceased, 74 (10.6%) from CVD causes. All calcified plaque scores were significantly associated with all-cause (HR: 1.4-1.8; p < 1x10(-5)) and CVD-mortality (HR: 1.5-1.9; p < 1×10(-4)) following adjustment for Framingham risk factors. Associations were strongest for coronary calcified plaque. Improvement in prediction of outcome beyond Framingham risk factors was greatest using coronary calcified plaque for all-cause mortality (AUC: 0.720 to 0.757, p = 0.004) and the multi-bed score for CVD mortality (AUC: 0.731 to 0.767, p = 0.008). CONCLUSIONS: Although coronary calcified plaque and the multi-bed score were the strongest predictors of all-cause mortality and CVD-mortality respectively in this T2D-affected sample, carotid and abdominal aortic calcified plaque scores also significantly improved prediction of outcome beyond traditional risk factors and should not be discounted as risk stratification tools.

Relationships of elevated systemic pentraxin-3 levels with high-risk coronary plaque components and impaired myocardial perfusion after percutaneous coronary intervention in patients with ST-elevation acute myocardial infarction.

BACKGROUND: We aimed to assess the relationships of pentraxin-3 (PTX3) with coronary plaque components and myocardial perfusion after percutaneous coronary intervention (PCI) in order to clarify the mechanisms underlying the prognostic function of PTX3 in ST-elevation acute myocardial infarction (STEMI) patients. METHODS AND RESULTS: We enrolled 75 STEMI patients who underwent pre-PCI virtual histology (VH)-intravascular ultrasound. Relationships of the systemic pre-PCI PTX3 level with coronary plaque components and post-PCI myocardial blush grade (MBG) were evaluated. Lesions with elevated pre-PCI PTX3 (median ≥3.79ng/ml) had higher frequencies of VH-derived thin-cap fibroatheroma (65.8% vs. 24.3%, P<0.0001), plaque rupture (63.2% vs. 24.3%, P=0.001), and post-PCI MBG (0-1) (65.8% vs. 40.5%, P=0.03) than those with PTX3 <3.79ng/ml. In multivariate analysis, pre-PCI PTX3 level was independently related to post-PCI MBG (0-1) (odds ratio, 11.385; 95% confidence interval (CI), 1.346-96.289; P=0.026). At 9-month follow-up, cardiac event-free survival was poorer for patients with post-PCI MBG (0-1) (log-rank test χ(2)=8.6; P=0.003). Cox proportional-hazards analysis showed post-PCI MBG (0-1) (hazard ratio, 4.109; 95% CI, 1.372-12.309; P=0.012) and Killip class >2 on admission (hazard ratio, 5.356; 95% CI, 1.409-20.359; P=0.014) as independent predictors of adverse cardiac events during follow-up. CONCLUSIONS: Systemic pre-PCI PTX3 was associated with high-risk plaque components and impaired post-PCI myocardial perfusion. Thus, PTX3 may be a reliable predictor of outcome in STEMI patients.

Coronary atheroma volume and cardiovascular events during maximally intensive statin therapy.

AIMS: The impact of baseline coronary plaque burden on the clinical outcome in patients receiving aggressive low-density lipoprotein cholesterol (LDL-C) lowering therapy to levels <70 mg/dL is unknown. We assessed the prognostic significance of baseline coronary plaque burden following high-intensity statin therapy. METHODS AND RESULTS: SATURN used serial intravascular ultrasound (IVUS) to measure coronary atheroma volume in 1039 patients before and after 24 months of treatment with rosuvastatin 40 mg or atorvastatin 80 mg. This post hoc analysis compared the relationship between baseline percent atheroma volume (PAV) and major adverse cardiovascular events (MACE: death, myocardial infarction, stroke, coronary revascularization, hospitalization for unstable angina) in patients with baseline PAV less than (n = 519) or greater than (n = 520) the median. Patients with a higher baseline PAV had a similar LDL-C compared with those with a lower baseline PAV at baseline (119.0 ± 29 vs. 121.0 ± 27 mg/dL, P = 0.09) and at follow-up (65.3 ± 23 vs. 65.8 ± 22 mg/dL, P = 0.47). In multivariable analysis, each standard deviation increase in baseline PAV was associated with a 28% increase in MACE [HR 1.28 (1.05, 1.57), P = 0.01]. Those with the highest quartile of baseline PAV (>41.8%) had a 2-year cumulative MACE rate of 12%, which was significantly higher (log-rank P = 0.001) than MACE rates of all lower PAV quartiles (MACE: quartile 3, 2, and 1 were 5.7, 7.9, and 5.1%, respectively). LDL-C levels at baseline [HR 0.96 (0.79, 1.18), P = 0.73] and on-treatment [HR 1.19 (0.83, 1.73), P = 0.35] were not associated with MACE. CONCLUSION: Following 2 years of high-intensity statin therapy, a baseline coronary atheroma volume predicted MACE, despite the achievement of very low on-treatment LDL-C levels.

[Pathogenesis of plaque destabilization induced by PM2.5 exposure and coping strategies].

With the increasingly more serious environmental pollution in China in recent years, effective intervention with PM25-induced health risks has become a major scientific issue to be addressed urgently in medical research field in China. NOD-like receptors (NLRs) are a family of cytoplasmic pattern-recognition receptors that have critical roles in innate immunity. On the basis of study progresses in international cardiovascular disease research "Fine particulate matter exposure is a modifiable risk factor for the morbidity and mortality of cardiovascular diseases", and with reference to the current understanding of pulmonary inflammation and oxidative stress in PM2.5-induced acute coronary syndrome, this study intended to investigate whether intracellular pattern recognition NL-RP3 plays a important role in the inital event of PM2.5 induced vessel inflammation as a foreign matter in the process of plaque destabilization and to thoroughly explore the underlying mechanisms responsible for PM2.5-induced acute cardiovascular events. On the other hand, it also studies the feasibility of using traditional Chinese medicine to treat plaque destabilization cause by PM2.5 exposure and discuss it's pathogenesis and intervention strategy based on TCM theory. This paper in order to provide scientific basis for social focal issues in public health proactively and offers the references for relevant research.

Impact of HDL genetic risk scores on coronary artery calcified plaque and mortality in individuals with type 2 diabetes from the Diabetes Heart Study.

BACKGROUND: Patients with type 2 diabetes (T2D) are at elevated risk for cardiovascular disease (CVD) events and mortality. Recent studies have assessed the impact of genetic variants affecting high-density lipoprotein cholesterol (HDL) concentrations on CVD risk in the general population. This study examined the utility of HDL-associated single nucleotide polymorphisms (SNPs) for CVD risk prediction in European Americans with T2D enrolled in the Diabetes Heart Study (DHS). METHODS: Genetic risk scores (GRS) of HDL-associated SNPs were constructed and evaluated for potential associations with mortality and with coronary artery calcified atherosclerotic plaque (CAC), a measure of subclinical CVD strongly associated with CVD events and mortality. Two sets of SNPs were used to construct GRS; while all SNPs were selected primarily for their impacts on HDL, one set of SNPs had pleiotropic effects on other lipid parameters, while the other set lacked effects on low-density lipoprotein cholesterol (LDL) or triglyceride concentrations. RESULTS: The GRS were specifically associated with HDL concentrations (4.90 × 10(-7) < p < 0.02) in models adjusted for age, sex, and body mass index (BMI), but were not associated with LDL or triglycerides. Cox proportional hazards regression analysis suggested the HDL-associated GRS had no impact on risk of CVD-mortality (0.48 < p < 0.99) in models adjusted for other known CVD risk factors. However, associations between several of the GRS and CAC were observed (3.85 × 10(-4) < p < 0.03) in models adjusted for other known CVD risk factors. CONCLUSIONS: The GRS analyzed in this study provide a tool for assessment of HDL-associated SNPs and their impact on CVD risk in T2D. The observed associations between several of the GRS and CAC suggest a potential role for HDL-associated SNPs on subclinical CVD risk in patients with T2D.

Glomerular filtration rate and albuminuria predict mortality independently from coronary artery calcified plaque in the Diabetes Heart Study.

BACKGROUND: Risk stratification in individuals with type 2 diabetes (T2D) remains an important priority in the management of associated morbidity and mortality, including from cardiovascular disease (CVD). The current investigation examined whether estimated glomerular filtration rate (eGFR) and urine albumin:creatinine ratio (UACR) were independent predictors of CVD-mortality in European Americans (EAs) with T2D after accounting for subclinical CVD. METHODS: The family-based Diabetes Heart Study (DHS) cohort (n=1,220) had baseline measures of serum creatinine, eGFR, UACR and coronary artery calcified plaque (CAC) assessed by non-contrast computed tomography scan. Cox proportional hazards regression was performed to determine risk for all-cause mortality and CVD-mortality associated with indices of kidney disease after accounting for traditional CVD risk factors and CAC as a measure of subclinical CVD. RESULTS: Participants were followed for 8.2±2.6 years (mean±SD) during which time 247 (20.9%) were deceased, 107 (9.1%) from CVD. Univariate analyses revealed positive associations between serum creatinine (HR:1.56; 95% CI:1.37-1.80; p<0.0001) and UACR (1.59; 1.43-1.77; p>0.0001) and negative associations between serum albumin (0.74; 0.65-0.84; p<0.0001) and eGFR (0.66; 0.58-0.76; p<0.0001) with all-cause mortality. Associations remained significant after adjustment for traditional CVD risk factors, as well as for CAC. Similar trends were noted when predicting risk for CVD-mortality. CONCLUSIONS: The DHS reveals that kidney function and albuminuria are independent risk factors for all-cause mortality and CVD-mortality in EAs with T2D, even after accounting for CAC.

Aortic atherosclerotic plaque and long-term prognosis in patients with atrial fibrillation-a transesophageal echocardiography study.

BACKGROUND: Both left atrial spontaneous echo contrast (LASEC) and aortic atherosclerotic plaque (AoP) ≥ 4.0 mm in thickness are predictors of cardiovascular events after stroke. The aim of this study was to investigate impact of AoP ≥ 4.0 mm or LASEC on cardiovascular events in patients with atrial fibrillation (AF). METHODS AND RESULTS: One hundred and eight consecutive patients with AF were enrolled and studied. Patients were grouped according to the presence or absence of AoP ≥ 4.0 mm in the proximal aortic arch on transesophageal echocardiography (TEE). Cardiovascular events included death, myocardial infarction, ischemic stroke, systemic embolism and congestive heart failure. During a follow-up period (median, 3.9 years), cardiovascular event-free survival rate was significantly lower in patients with AoP ≥ 4.0 mm than in patients without AoP ≥ 4.0 mm (log-rank, P=0.01). In contrast, patients with LASEC showed a trend toward lower cardiovascular event-free survival than those without LASEC (log-rank, P=0.10). Univariate TEE predictors of cardiovascular events were AoP ≥ 4.0 mm, LASEC and left atrial appendage flow velocity. On multivariate Cox regression analysis, AoP ≥ 4.0 mm was the only TEE predictor of cardiovascular events during follow-up (P=0.02, hazard ratio, 2.6; 95% confidence interval: 1.1-6.0). CONCLUSIONS: In the present unselected patients with AF, AoP predicted long-term cardiovascular events.

Common carotid artery intima-media thickness is as good as carotid intima-media thickness of all carotid artery segments in improving prediction of coronary heart disease risk in the Atherosclerosis Risk in Communities (ARIC) study.

AIMS: Carotid intima-media thickness (CIMT) and plaque information can improve coronary heart disease (CHD) risk prediction when added to traditional risk factors (TRF). However, obtaining adequate images of all carotid artery segments (A-CIMT) may be difficult. Of A-CIMT, the common carotid artery intima-media thickness (CCA-IMT) is relatively more reliable and easier to measure. We evaluated whether CCA-IMT is comparable to A-CIMT when added to TRF and plaque information in improving CHD risk prediction in the Atherosclerosis Risk in Communities (ARIC) study. METHODS AND RESULTS: Ten-year CHD risk prediction models using TRF alone, TRF + A-CIMT + plaque, and TRF + CCA-IMT + plaque were developed for the overall cohort, men, and women. The area under the receiver operator characteristic curve (AUC), per cent individuals reclassified, net reclassification index (NRI), and model calibration by the Grønnesby-Borgan test were estimated. There were 1722 incident CHD events in 12 576 individuals over a mean follow-up of 15.2 years. The AUC for TRF only, TRF + A-CIMT + plaque, and TRF + CCA-IMT + plaque models were 0.741, 0.754, and 0.753, respectively. Although there was some discordance when the CCA-IMT + plaque- and A-CIMT + plaque-based risk estimation was compared, the NRI and clinical NRI (NRI in the intermediate-risk group) when comparing the CIMT models with TRF-only model, per cent reclassified, and test for model calibration were not significantly different. CONCLUSION: Coronary heart disease risk prediction can be improved by adding A-CIMT + plaque or CCA-IMT + plaque information to TRF. Therefore, evaluating the carotid artery for plaque presence and measuring CCA-IMT, which is easier and more reliable than measuring A-CIMT, provide a good alternative to measuring A-CIMT for CHD risk prediction.