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.).

Predictive value of spiral shape in coronary plaque progression: an intraindividual comparative study.

OBJECTIVE: We conducted a pilot study to explore the value of spiral-shaped sign of plaque from coronary computed tomographic angiography (CCTA) in predicting plaque progression by intraindividual comparison. METHODS: A total of 30 patients with a total of 60 plaques who received serial CCTA were retrospectively included and intraindividual compared. The spiral shape was defined as plaques coursing along the long axis of a coronary artery and encircling it at an angle of ≥ 180 degrees. The high-risk and other plaque signs were recorded. RESULTS: On baseline CCTA, the spiral shape (P < 0.01) and length (P < 0.05) of plaques were more frequently seen in the progression group than in the nonprogression group; however, there was no difference between two groups in terms of high-risk plaque signs. In the progression group, plaque length, volume, and napkin-ring sign on follow-up CCTA were significantly greater than at baseline (P < 0.05). In the nonprogression group, there were fewer low-attenuation and positive remodeling plaques on follow-up CCTA than at baseline (P < 0.05). The spiral shape (standardized ß = -4.55; P < 0.01) was an independent risk factor for plaque progression. There were 24 spiral plaques in the progression group, of which 16 (66.7%) had progression below the twist point of the spiral shape. CONCLUSIONS: The baseline spiral shape is more frequently found in those lesions that progress than in those that do not in patients with multiple coronary lesions, and the spiral shape is an independent predictor of which plaques will progress.

Effects of Anthocyanins on Vascular Health.

Cardiovascular disorders are leading mortality causes worldwide, often with a latent evolution. Vascular health depends on endothelial function, arterial stiffness, and the presence of atherosclerotic plaques. Preventive medicine deserves special attention, focusing on modifiable cardiovascular risk factors, including diet. A diet rich in fruits and vegetables has well-known health benefits, especially due to its polyphenolic components. Anthocyanins, water-soluble flavonoid species, responsible for the red-blue color in plants and commonly found in berries, exert favorable effects on the endothelial function, oxidative stress, inhibit COX-1, and COX-2 enzymes, exert antiatherogenic, antihypertensive, antiglycation, antithrombotic, and anti-inflammatory activity, ameliorate dyslipidemia and arterial stiffness. The present review aims to give a current overview of the mechanisms involved in the vascular protective effect of anthocyanins from the human diet, considering epidemiological data, in vitro and in vivo preclinical research, clinical observational, retrospective, intervention and randomized studies, dietary and biomarker studies, and discussing preventive benefits of anthocyanins and future research directions.

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.

Impact of Plaque Burden Versus Stenosis on Ischemic Events in Patients With Coronary Atherosclerosis.

BACKGROUND: Patients with obstructive coronary artery disease (CAD) are at high risk for cardiovascular disease (CVD) events. However, it remains unclear whether the high risk is due to high atherosclerotic disease burden or if presence of stenosis has independent predictive value. OBJECTIVES: The purpose of this study was to evaluate if obstructive CAD provides predictive value beyond its association with total calcified atherosclerotic plaque burden as assessed by coronary artery calcium (CAC). METHODS: Among 23,759 symptomatic patients from the Western Denmark Heart Registry who underwent diagnostic computed tomography angiography (CTA), we assessed the risk of major CVD (myocardial infarction, stroke, and all-cause death) stratified by CAC burden and number of vessels with obstructive disease. RESULTS: During a median follow-up of 4.3 years, 1,054 patients experienced a first major CVD event. The event rate increased stepwise with both higher CAC scores and number of vessels with obstructive disease (by CAC scores: 6.2 per 1,000 person-years (PY) for CAC = 0 to 42.3 per 1,000 PY for CAC >1,000; by number of vessels with obstructive disease: 6.1 per 1,000 PY for no CAD to 34.7 per 1,000 PY for 3-vessel disease). When stratified by 5 groups of CAC scores (0, 1 to 99, 100 to 399, 400 to 1,000, and >1,000), the presence of obstructive CAD was not associated with higher risk than presence of nonobstructive CAD. CONCLUSIONS: Plaque burden, not stenosis per se, is the main predictor of risk for CVD events and death. Thus, patients with a comparable calcified atherosclerosis burden generally carry a similar risk for CVD events regardless of whether they have nonobstructive or obstructive CAD.

Carotid Lumen Diameter Is Associated With All-Cause Mortality in the General Population.

Background Common carotid intima-media thickness (cIMT) is a biomarker for subclinical atherosclerosis and is associated with all-cause as well as cardiovascular mortality. Higher cIMT is accompanied by a compensatory increase in lumen diameter (LD) of the common carotid arteries. Whether cIMT or LD carry more information with regard to mortality is unclear. Methods and Results A total of 2751 subjects (median age 53 years; 52% female) were included. During a median follow-up of 14.9 years (range: 12.8-16.5) a total of 506 subjects died. At baseline, cIMT and LD were assessed by carotid ultrasound scans. Multivariable Cox regression models were used to relate cIMT, LD, LD adjusted for cIMT (LD+cIMT), and LD/cIMT ratio with all-cause, cardiovascular, and noncardiovascular mortality. All models were ranked using Akaike's information criterion. Harrel's c statistic was used to compare the models' predictive power for mortality. A 1-mm increase in LD was related to a higher risk for all-cause mortality (hazard ratio [HR], 1.29; 95% CI, 1.14-1.45, P<0.01). This association remained significant when cIMT was added to the model (HR, 1.26; 95% CI, 1.11-1.42; P<0.01). A 1-mm higher cIMT was also related with greater mortality risk (HR, 1.73; 95% CI, 1.09-2.75). The LD/cIMT ratio was not associated with all-cause mortality. LD had the lowest Akaike's information criterion regarding all-cause mortality and improved all-cause mortality prediction compared with the null model (P=0.01). CIMT weakened all-cause mortality prediction compared with the LD model. Conclusions LD provided more information for all-cause mortality compared with cIMT in a large population-based sample.

Combined effects of carotid plaques and hypertension on the risk of cardiovascular disease and all-cause mortality.

BACKGROUND: Both hypertension and atherosclerotic plaques are risk factors for cardiovascular disease (CVD). HYPOTHESIS: This study aimed to investigate whether the combined effects of carotid plaques and hypertension increase the risks of CVD and all-cause mortality. METHODS: Patients from the stroke and elderly cohorts of the Kailuan study in China who completed a carotid sonography examination were included in the study. Participants in both cohorts underwent physical examinations between 2010 and 2011 and were divided into four groups: no carotid plaques with normal blood pressure (n = 2227), hypertension only (n = 1290), carotid plaques only (n = 1128), and hypertension with carotid plaques (n = 1862). The outcomes included the first occurrence of CVD and all-cause mortality. RESULTS: Among the 6507 participants (mean age, 58.1 ± 11.8 years, 61% males), 157 cardiovascular events, and 210 deaths occurred after average follow-ups of 4.5 and 4.9 years, respectively. After adjusting for covariates, carotid plaques only and hypertension with carotid plaques were associated with excess risk (hazard ratio [HR]; confidence interval [CI]) for the first occurrence of CVD (HR = 1.85; 95% CI, 1.01-3.44; and HR = 2.97; 95% CI, 1.66-5.29, respectively), cerebral infarction (HR = 2.66; 95% CI, 1.16-6.15; and HR = 4.15; 95% CI, 1.87-9.19, respectively), and all-cause mortality (HR = 1.96; 95% CI, 1.16-3.31; and HR = 1.85; 95% CI, 1.09-3.13, respectively). CONCLUSIONS: The combination of hypertension and atherosclerotic plaques may increase the risk of CVD events and all-cause mortality, especially cerebral infarction, compared with participants without those factors.

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.

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.

Impact of Coronary Computerized Tomography Angiography-Derived Plaque Quantification and Machine-Learning Computerized Tomography Fractional Flow Reserve on Adverse Cardiac Outcome.

This study investigated the impact of coronary CT angiography (cCTA)-derived plaque markers and machine-learning-based CT-derived fractional flow reserve (CT-FFR) to identify adverse cardiac outcome. Data of 82 patients (60 ± 11 years, 62% men) who underwent cCTA and invasive coronary angiography (ICA) were analyzed in this single-center retrospective, institutional review board-approved, HIPAA-compliant study. Follow-up was performed to record major adverse cardiac events (MACE). Plaque quantification of lesions responsible for MACE and control lesions was retrospectively performed semiautomatically from cCTA together with machine-learning based CT-FFR. The discriminatory value of plaque markers and CT-FFR to predict MACE was evaluated. After a median follow-up of 18.5 months (interquartile range 11.5 to 26.6 months), MACE was observed in 18 patients (21%). In a multivariate analysis the following markers were predictors of MACE (odds ratio [OR]): lesion length (OR 1.16, p = 0.018), low-attenuation plaque (<30 HU) (OR 4.59, p = 0.003), Napkin ring sign (OR 2.71, p = 0.034), stenosis ≥50% (OR 3.83, p 0.042), and CT-FFR ≤0.80 (OR 7.78, p = 0.001). Receiver operating characteristics analysis including stenosis ≥50%, plaque markers and CT-FFR ≤0.80 (Area under the curve 0.94) showed incremental discriminatory power over stenosis ≥50% alone (Area under the curve 0.60, p <0.0001) for the prediction of MACE. cCTA-derived plaque markers and machine-learning CT-FFR demonstrate predictive value to identify MACE. In conclusion, combining plaque markers with machine-learning CT-FFR shows incremental discriminatory power over cCTA stenosis grading alone.

Age-dependent association of gut bacteria with coronary atherosclerosis: Tampere Sudden Death Study.

BACKGROUND: The gut microbiome is thought to remain stable into old age. Gut bacteria and their translocation may play a role in the development of coronary heart disease (CHD) by modulating cholesterol levels and immune responses, as well as by producing toxic metabolites and bacterial endotoxins. The association of changes in the gut microbiome with the severity of coronary atherosclerosis and the ability of gut bacteria themselves to translocate into coronary plaques has not been studied. MATERIALS AND METHODS: As a part of the Tampere Sudden Death Study, we measured age-dependent changes in the relative ratios of major intestinal bacterial communities (Bacteroides species [spp.], the Clostridium leptum group, the Clostridium coccoides group, Bifidobacterium spp., Enterobactericeae, Lactobacillus spp.) and Streptococcus spp. in both feces and coronary plaques of the same male autopsy cases (n = 67, age range 44-95) using real-time quantitative PCR (qPCR). The area of coronary atherosclerotic lesions were measured by computer-assisted morphometry. Fecal bacterial DNA measurements from healthy volunteers served as a control for gut bacterial analyses of autopsy cases. The relative amount of bacterial DNA in a sample was determined with the comparative Cq method. RESULTS: The relative ratios of fecal Lactobacillus spp., Bifidobacterium spp., the Clostridium coccoides group, and Bacteroides spp. did not differ between controls and autopsy cases and showed no age-dependence. In contrast, the ratios of the Clostridium leptum group, Enterobactericeae, and Streptococcus spp. increased with age. Elevated relative ratios of fecal Enterobactericeae associated with a larger coronary plaque fibrotic area (p = 0.001), and the Clostridium leptum group with a larger calcification area (p = 0.015). Intestinal bacterial DNA could be amplified in 67.6% of the coronary plaques, the most common being Streptococcus spp. (41.0%), followed by Enterobactericeae (12.1%), Clostridium leptum (2.4%), and Lactobacillus spp. (2.4%). The percentages of Streptococcus spp. DNA decreased, and those of Enterobactericeae increased in coronary plaques along with age. CONCLUSIONS: DNA of the Clostridium leptum group and pathogenic Enterobactericeae increase in the gut microbiome with age and can be detected in the same individual's coronary plaques along with pathogenic Streptococcus spp., associating with more severe coronary atherosclerosis.

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.

Comparison of Coronary Culprit Lesion Morphology Determined by Optical Coherence Tomography and Relation to Outcomes in Patients Diagnosed with Acute Coronary Syndrome During Winter -vs- Other Seasons.

Patients diagnosed with acute coronary syndrome (ACS) during winter have worse outcomes; however, mechanisms driving this trend are unclear. We examined coronary culprit lesion morphologies using optical coherence tomography (OCT). Features and outcomes were retrospectively compared between patients admitted with ACS in winter (W-ACS; n = 390) and in other seasons (O-ACS; n = 1,027). Angiography and OCT results were analyzed in patients who underwent OCT examination (173 patients in W-ACS and 450 in O-ACS). On initial angiography, minimum lumen diameter was smaller (median; 0.12 mm vs 0.25 mm, p = 0.021) and Thrombolysis in myocardial infarction flow grade was worse (Thrombolysis in myocardial infarction 0/1; 57% vs 44%, p = 0.005) in W-ACS. OCT performed before coronary interventions or just after intracoronary thrombectomy showed that plaque rupture (56% vs 46%) and calcified nodules (8% vs 5%) were more prevalent, and plaque erosion (37% vs 49%) was less prevalent in W-ACS (p = 0.039 for all 3 variables). At 2-year follow-up for all admitted ACS patients, Kaplan-Meier estimates showed higher cardiac mortality in W-ACS (11.8% vs 8.3%, p = 0.043). Multivariate Cox proportional hazard analysis showed that patients in W-ACS group had a 1.5-fold increased risk of cardiac death within 2 years after adjusting for traditional cardiovascular risk factors (hazard ratio, 1.54 [95% confidence interval, 1.06 to 2.23]; p = 0.024). In conclusion, patients diagnosed with ACS during winter had worse angiographic results and OCT revealed less plaque erosion (more plaque rupture or calcified nodules) at the culprit lesions, which may be partly associated with worse cardiac mortality within 2 years.

Lecciones aprendidas mediante el estudio de las placas ateroscleróticas obtenidas en las necropsias / Lessons learned by atherosclerotic plaques at necropsy

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Low-speed rotational atherectomy with substantial debulking and long-term survival: a retrospective observational study of 889 consecutive patients.

BACKGROUND In recent years, a series of studies have investigated long-term outcome of rotational atherectomy (RA). However, only little attention was given to the procedural details of RA technique, especially with regard to platform speed. AIMS The aim of the study was to evaluate the impact of low-speed RA with substantial debulking before stenting on long-term mortality. METHODS A group of 356 patients with a high plaque burden underwent substantial debulking with RA with low platform speed of 135 000 rpm and was compared with a group of 553 patients treated without RA in the same time period. In both cohorts lesion preparation was followed by stent implantation. The endpoint was all-cause mortality up to 80 months with a mean (SD) follow-up of 49 (24) months. RESULTS Despite the fact that patients treated with RA were significantly older and presented more unfavorable lesion characteristics than non-RA patients, there was no significant difference in long-term survival between groups. A propensity analysis with 279 matched pairs showed that long-time survival in RA patients was better than in non-RA patients (hazard ratio, 0.52; CI, 0.32-0.85; P <0.01). CONCLUSIONS Substantial debulking with RA continues to play a role in the treatment of calcified coronary arteries. We hypothesize that RA with low platform speed and substantial debulking with a burr-to-artery ratio of up to 0.64 results in favorable long-time survival in patients with high plaque burden. However, this can only be proved in a prospective randomized trial.

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.

Qualitative evaluation of coronary atherosclerosis in a large cohort of young and middle-aged Dutch tissue donors implies that coronary thrombo-embolic manifestations are stochastic.

BACKGROUND AND AIMS: With the intention to gain support for the hypothesis that incident ischemic complications of atherosclerotic disease involve a stochastic aspect, we performed a histological, qualitative evaluation of the epidemiology of coronary atherosclerotic disease in a cohort of aortic valve donors. PATIENTS AND METHODS: Donors (n = 695, median age 54, range 11-65 years) were dichotomized into a non-cardiovascular (non-CVD) and a cardiovascular disease death (CVD) group. Consecutive 5 mm proximal left coronary artery segments were Movat stained, and the atherosclerotic burden for each segment was graded (revised AHA-classification). RESULTS: Non-CVD and CVD groups showed steep increase of atherosclerosis severity beyond the age of 40, resulting in an endemic presence of advanced atherosclerosis in men over 40 and women over 50 years. In fact, only 19% of the non-CVD and 6% of the CVD donors over 40 years were classified with a normal LCA or a so called non-progressive lesion type. Fibrous calcified plaques (FCP), the consolidated remnants of earlier ruptured lesions, dominated in both non-CVD and CVD donors. Estimates of the atherosclerosis burden (i.e. average lesion grade, proportion of FCPs, and average number of FCPs per cross-section) were all higher in the CVD group (p<1.10-16, p<0.0001, and p<0.05, respectively). CONCLUSIONS: Dominance of consolidated FCP lesions in males over 40 and females over 50 years, show that plaque ruptures in the left coronary artery are common. However, the majority of these ruptures remain asymptomatic. This implies that the atherosclerotic process is repetitive. A relative difference in disease burden between CVD and non-CVD donors supports the concept that complications of atherosclerotic disease involve a stochastic element.

Increased glycoprotein acetylation is associated with high cardiac event rates: Analysis using coronary computed tomography angiography.

OBJECTIVE: Glycoprotein acetylation (GlycA), an emerging inflammatory biomarker, has been used as an indicator of cardiovascular disease. Our research aimed to evaluate the correlation between GlycA and coronary artery disease (CAD) using coronary computed tomography angiography (CCTA). METHODS: In the present study, a total of 342 patients were enrolled, and each of them underwent CCTA. The correlation between GlycA and major adverse cardiac events (MACE) was detected via Cox's proportional hazards models. Based on differences in the GlycA level, patients were categorized into three groups (T1, T2, and T3). RESULTS: Compared with the group with the lowest GlycA level (T1), the group with the highest GlycA level (T3) exhibited stronger atherosclerotic pressure involving the extent of atherosclerotic plaque and risk of obstructive CAD. In addition, the patients in the T3 group had a greater chance of experiencing MACE and higher all-cause mortality than those in the T1 group. Among patients without CAD who underwent CCTA, those with high GlycA levels experienced elevated atherosclerotic stress and heightened risk of MACE compared with those with low GlycA levels. CONCLUSION: These results suggest that serum GlycA is significantly associated with the long-term clinical results of patients with no known CAD undergoing CCTA. The risks of death and experiencing MACE increase among patients with high GlycA levels.

Quantitative Extent of Atherosclerotic Plaque in the Major Epicardial Coronary Arteries in Patients with Fatal Coronary Heart Disease, in Coronary Endarterectomy Specimens, in Aorta-Coronary Saphenous Venous Conduits, and Means to Prevent the Plaques: A Review after Studying the Coronary Arteries for 50 Years.

This review tries to answer the following 15 questions: Is atherosclerosis a systemic or a regional disease? Is atherosclerosis in any particular region focal or diffuse? What is the quantity of atherosclerotic plaques in endarterectomy specimens of the right coronary artery in patients undergoing coronary artery bypass grafting (CABG) compared to that in the right coronary artery in patients with fatal coronary artery disease? How do the units used for measuring arterial narrowing by angiography compare to the units used for measuring arterial narrowing at necropsy? What do atherosclerotic plaques consist of in coronary arteries in patients with fatal coronary disease? What is the quantity of atherosclerotic plaque in bypassed -vs- non-bypassed native coronary arteries in patients dying early (<60 days) or late (>60 days) after coronary artery bypass grafting? What is the frequency of acute coronary lesions and multi-luminal channels at necropsy in patients with unstable angina pectoris, sudden coronary death, and acute myocardial infarction? What is the mechanism of luminal widening by angioplasty in the coronary arteries? What observations suggest that atherosclerotic plaques are the result at least in part of organization of thrombi? Is atherosclerosis a multifactoral or a unifactoral disease? What characteristics distinguish carnivores and herbivores? What are reasonable guidelines for whom to treat with lipid-altering agents? What is the rule of 5 and the rule of 7 in statin therapy? What is the effect of lipid lowering drug therapy on coronary luminal narrowing? What are some requisites for a healthy life?

Relation of Coronary Culprit Lesion Morphology Determined by Optical Coherence Tomography and Cardiac Outcomes to Serum Uric Acid Levels in Patients With Acute Coronary Syndrome.

The aims of the present study were to elucidate features of culprit lesion plaque morphology using optical coherence tomography (OCT) in relation to elevated serum uric acid (sUA) levels and to clarify the impact of sUA levels on adverse clinical outcomes in patients with acute coronary syndrome (ACS). Clinical data and outcomes were compared between ACS patients with sUA ≥6 mg/dl (high-sUA; n = 506) and sUA <6.0 mg/dl (low-sUA; n = 608). Angiography and OCT findings were analyzed in patients with preintervention OCT and compared between groups of high-sUA (n = 206) and low-sUA (n = 273). Patients with high-sUA were more frequently male (88% vs 74%, p <0.001), younger (median 65 years vs 67 years, p = 0.017), more obese (median body mass index; 24.3 kg/m2 vs 23.2 kg/m2, p <0.001), and had a more frequent history of hypertension (72% vs 62%, p <0.001). ACS with lung congestion or cardiogenic shock was more prevalent in patients with high-sUA (30% vs 13%, p <0.001). Plaque rupture (54% vs 42%, p = 0.021) and red thrombi (55% vs 41%, p = 0.010) were more prevalently observed by OCT in patients with high-sUA. Kaplan-Meier estimate survival curves showed that the 2-year cardiac mortality was higher in patients with high-sUA (12.1% vs 4.2%, p <0.001). The multivariate Cox proportional hazard analysis showed that sUA values independently and significantly predicted cardiac death within 2 years (hazard ratio 1.41 [95% confidence interval 1.26 to 1.57], p <0.001). In conclusion, sUA levels are associated with culprit lesion coronary plaque morphology and raised sUA levels affect cardiovascular mortality after adjusting for several cardiovascular risk factors.