Plaque volume and plaque risk profile in diabetic vs. non-diabetic patients undergoing lipid-lowering therapy: a study based on 3D intravascular ultrasound and virtual histology

Background

Coronary atherosclerosis progresses faster in patients with diabetes mellitus (DM) and causes higher morbidity and mortality in such patients compared to non-diabetics ones (non-DM). We quantify changes in plaque volume and plaque phenotype during lipid-lowering therapy in DM versus non-DM patients using advanced intracoronary imaging.

Methods

We analyzed data from 61 patients with stable angina pectoris included to the PREDICT trial searching for prediction of plaque changes during intensive lipid-lowering therapy (40 mg rosuvastatin daily). Geometrically correct, fully 3-D representation of the vascular wall surfaces and intravascular ultrasound virtual histology (IVUS-VH) defined tissue characterization was obtained via fusion of two-plane angiography and IVUS-VH. Frame-based indices of plaque morphology and virtual histology analyses were computed and averaged in 5 mm long baseline/follow-up registered vessel segments covering the entire length of the two sequential pullbacks (baseline, 1-year). We analyzed 698 5-mm-long segments and calculated the Liverpool active plaque score (LAPS).

Results

Despite reaching similar levels of LDL cholesterol (DM 2.12 ± 0.91 mmol/l, non-DM 1.8 ± 0.66 mmol/l, p = 0.21), DM patients experienced, compared to non-DM ones, higher progression of mean plaque area (0.47 ± 1.15 mm² vs. 0.21 ± 0.97, p = 0.001), percent atheroma volume (0.7 ± 2.8% vs. ? 1.4 ± 2.5%, p = 0.007), increase of LAPS (0.23 ± 1.66 vs. 0.13 ± 1.79, p = 0.018), and exhibited more locations with TCFA (Thin-Cap Fibro-Atheroma) plaque phenotype in 5 mm vessel segments (20.3% vs. 12.5%, p = 0.01). However, only non-DM patients reached significant decrease of LDL cholesterol. Plaque changes were more pronounced in PIT (pathologic intimal thickening) compared to TCFA with increased plaque area in both phenotypes in DM patients.

Conclusion

Based on detailed 3D analysis, we found advanced plaque phenotype and further atherosclerosis progression in DM patients despite the same reached levels of LDLc as in non-DM patients. Trial registration ClinicalTrials.gov identifier: NCT01773512

     

The Association of Brachial-Ankle Pulse Wave Velocity with Coronary Artery Disease Evaluated by Coronary Computed Tomography Angiography

The aim of this study was to investigate whether brachial-ankle pulse wave velocity (baPWV) is associated with the severity of coronary artery disease (CAD) assessed by coronary computed tomography angiography (CCTA), and to evaluate baPWV as a predictor of obstructive CAD on CCTA. A total of 470 patients who underwent both baPWV and CCTA were included. We evaluated stenosis degree and plaque characteristics on CCTA. To estimate the severity of CAD, we calculated the number of segment with plaque (segment involvement score; SIS), stenosis degree-weighted plaque score (segment stenosis score; SSS), and coronary artery calcium score (CACS). The mean baPWV was 1,485 ± 315 cm/s (range, 935-3,175 cm/s). Non-obstructive (stenosis < 50%) and obstructive (stenosis ≥ 50%) CAD was found in 129 patients (27.4%) and 144 (30.6%), respectively. baPWV in patients with obstructive CAD was higher than that of patients with non-obstructive (1,680 ± 396 cm/s versus 1,477 ± 244 cm/s, P < 0.001) or no CAD (1,680 ± 396 cm/s versus ± 196 1,389 cm/s, P < 0.001). baPWV showed significant correlation with SSS (r = 0.429, P < 0.001), SIS (r = 0.395, P < 0.001), CACS (r 0.346, P < 0.001), and the number of segment with non-calcified plaque (r 0.092, P = 0.047), mixed plaque (r = 0.267, P < 0.001), and calcified plaque (r = 0.348, P < 0.001), respectively. The optimal baPWV cut-off value for the detection of obstructive CAD was 1,547 cm/s. baPWV ≥ 1,547 cm/s was independent predictor for the obstructive CAD. In conclusion, baPWV is well correlated with the severity of CAD evaluated by CCTA. baPWV has the potential to predict severity of coronary artery atherosclerosis.     

Association of secreted frizzled-related protein 4 (SFRP4) with type 2 diabetes in patients with stable coronary artery disease

Background

The interplay between the novel adipokine retinol-binding protein-4 (RBP4) and coronary artery disease (CAD) is still obscure. We investigated the relationship between RBP4 levels and the presence and severity of angiographically proven CAD and determined its possible role in acute myocardial infarction (AMI).

Methods

305 individuals with angiographically proven CAD (CAD-patients), were classified into 2 subgroups: 1) acute myocardial infarction (AMI, n = 141), and 2) stable angina (SA, n = 164). Ninety-one age- and sex-matched individuals without CAD, but with at least 2 classical cardiovascular risk factors, served as controls (non-CAD group). RBP4 serum levels were measured at hospital admission and were analyzed in relation to the coronary severity stenosis, assessed by the Gensini-score and the number of coronary narrowed vessels. Other clinical parameters, including insulin levels, HOMA-IR, hsCRP, glycaemic and lipid profile, and left-ventricular ejection fraction were also assessed.

Results

Serum RBP4 levels were significantly elevated in patients with CAD compared to non-CAD patients (39.29  ± 11.72 mg/L vs. 24.83  ± 11.27 mg/L, p < 0.001). We did not observe a significant difference in RBP4 levels between AMI and SA subgroups (p = 0.734). Logistic regression analysis revealed an independent association of CAD presence with serum RBP4 (β = 0.163, p = 0.006), and hsCRP (β = 0.122, p = 0.022) levels, in the whole study group. Among variables, hsCRP (β = 0.220), HDL (β = β0.150), and RBP4 (β = 0.297), correlated in both univariate and multivariate analysis with CAD severity (R² = 0.422, p < 0.001). Similarly, RBP4 concentrations increased with the number of coronary narrowed vessels (p < 0.05).

Conclusion

Patients with CAD, both SA and AMI, showed elevated RBP4 serum levels. Notably, increased RBP4 concentration seemed to independently correlate with CAD severity, but no with AMI.

Trial registration

The ClinicalTrials.gov Identifier is: NCT00636766

     

Increased Risk of Herpes Zoster in Diabetic Patients Comorbid with Coronary Artery Disease and Microvascular Disorders: A Population-Based Study in Taiwan

We investigated the association between the risk of herpes zoster (HZ) and diabetes-related macrovascular comorbidities and microvascular disorders in diabetic patients. This retrospective study included 25,345 patients with newly identified HZ and age- and gender-matched controls retrieved from the National Health Insurance Research Database in Taiwan during the period of 2005 to 2011. Multivariate logistic regression analyses were used to calculate the odds ratios (OR) and to assess the risk factors for HZ in diabetic patients with associated macrovascular or microvascular disorders. Risk factors for HZ were significantly increased in cases of diabetes mellitus (DM) compared with those in cases of non-DM controls (20.2% vs. 17.0%, OR = 1.24, p<0.001). Results of age- and gender-adjusted analyses demonstrated a significantly higher risk of HZ in DM patients with accompanying coronary artery disease (CAD) (adjusted OR = 1.21, p<0.001) and microvascular disorders (aOR = 1.32, p<0.001) than in DM patients with other comorbidities but no microvascular disorders. Patients who took thiazolidinedione, alpha-glucosidase inhibitors and insulin had a higher HZ risk than those taking metformin or sulphonylureas alone (aOR = 1.11, 1.14 and 1.18, p<0.001, respectively). Patients who took insulin alone or in combination with other antidiabetic agents had a significantly higher risk of HZ (aOR = 1.25, p<0.001) than those who received monotherapy. Diabetic patients comorbid with coronary artery disease and associated microvascular disorders had an increased risk of HZ occurrence.     

Asymmetric dimethylarginine and long-term adverse cardiovascular events in patients with type 2 diabetes: relation with the glycemic control

Patients with type 2 diabetes are at a high risk for acute cardiovascular events, which usually arise from the rupture of a vulnerable coronary lesion characterized by specific morphological plaque features. Thus, the identification of vulnerable plaques is of utmost clinical importance in patients with type 2 diabetes. However, there is currently no scoring system available to identify vulnerable lesions based on plaque characteristics. Thus, we aimed to characterize the diagnostic value of optical coherence tomography (OCT) - derived lesion characteristics to quantify plaque vulnerability both as individual parameters and when combined to a score in patients with type 2 diabetes. OCT was performed in the coronary culprit lesions of 112 patients with type 2 diabetes. The score, which quantifies plaque vulnerability, was defined as the predicted probability that a lesion is the cause for an acute coronary syndrome (ACS) (vs. stable angina (SAP)) based on its specific plaque morphology. Multivariable logistic regression analysis demonstrated that plaque vulnerability was independently predicted by the minimal fibrous cap thickness overlying a lesion’s lipid core (odds ratio (OR) per 10 μm 0.478, p = 0.002), the medium lipid arc (OR per 90° 13.997, p < 0.001), the presence of macrophages (OR 4.797, p = 0.015) and the lipid plaque length (OR 1.290, p = 0.098). Receiver-operating-characteristics (ROC) analyses demonstrated that these parameters combined to a score demonstrate an excellent diagnostic efficiency to identify culprit lesions of patients with ACS (vs. SAP, AUC 0.90, 95% CI 0.84-0.96). This is the first study to present a score to quantify lesion vulnerability in patients with type 2 diabetes. This score may be a valuable adjunct in decision-making and useful in guiding coronary interventions.     

Vitamin D Deficiency—Prognostic Marker or Mortality Risk Factor in End Stage Renal Disease Patients with Diabetes Mellitus Treated with Hemodialysis—A Prospective Multicenter Study

BackgroundEnd stage renal disease (ESRD) patients on renal replacement therapy (RRT) with diabetes mellitus (DM) have a higher mortality rate and an increase prevalence of vitamin D deficiency compared to those without DM. It is still debated if vitamin D deficiency is a risk factor or a prognostic marker for mortality in these patients. This study investigated the prevalence of vitamin D deficiency and its impact on all-cause mortality in HD patients with DM.MethodsOur prospective non-interventional cohort study included 600 patients on hemodialysis therapy (HD) (median aged 56, interquartile range (19) years, 332 (55.3%) males) recruited from 7 HD centers, from all main geographical regions of Romania. The prevalence of DM was 15.3%. They were then followed regarding: dialysis duration, dialysis efficiency, renal anemia, CKD-MBD, inflammatory status and comorbidities: coronary artery disease (CAD), peripheral vascular disease (PVD) and stroke. The deficiency of 25-OH vitamin D was defined as a value lower than12 ng/mL.ResultsPatients were followed for 3 years. The overall 3 year mortality was 25.5% (153 individuals), being higher in patients with DM as compared to those without DM (33.7% vs. 24.0%; P = 0.049). The time-related prognosis was also influenced by the presence of DM, at the survival analysis resulting in a HR of 1.52 [1.03 to 2.26] 95% CI, P = 0.037, for death in dialyzed patients with DM. In DM patients, 25-OH vitamin D deficiency was significantly higher (37.0% compared to 24.0%, P = 0.009). Furthermore, in patients with DM we observed a shorter dialysis duration (2 vs. 3 years, P<0.001) and a lower intact parathyroid hormone (iPTH) (258.0 pg/ml vs. 441.9 pg/ml, P = 0.002). Regarding the presence of comorbidities at the inclusion in the study, the presence of diabetes in dialyzed patients was associated with increased prevalence of CAD (87.0% vs. 58.1%, P<0.001), PVD (67.4% vs. 17.3%, P<0.001) and history of stroke (29.3% vs. 14.0%, P<0.001). In patients with DM the presence of 25-OH vitamin D deficiency increased the probability of death (50.0% vs. 24.1%; P = 0.011). In multiple Cox proportional hazards analysis, vitamin D deficiency remained an independent predictor for mortality in dialysis patients with DM (HR = 1.71, 95% CI 1.21 to 2.43, P = 0.003). In the same time, multiple Cox proportional hazards analysis showed that age (HR = 1.02 per one year increase, P = 0.004), CAD (HR = 1.55, P = 0.046) and PVD (HR = 1.50, P = 0.029) were independent predictors for mortality in dialysis patients with DM.ConclusionsESRD patients with DM treated with HD have a higher overall mortality than non-DM patients. Vitamin D deficiency is significantly more prevalent in HD patients with DM. Low 25-OH vitamin D levels were associated with increased all-cause mortality in these patients. According to our data, in HD patients with DM, screening for vitamin D deficiency (and its correction) should be mandatory for an optimal risk reduction strategy.     

Angiotensin II,as well as 5-hydroxytriptamine,is a potent vasospasm inducer of saphenous vein graft for coronary artery bypass grafting in patients with diabetes mellitus

Diabetes mellitus (DM) is an important risk factor for adverse outcomes of coronary artery bypass grafting. The bypass grafts harvested from patients with DM tend to go into spasm after their implantation into the coronary circulation. To clarify the contribution of 5-hydroxytriptamine (5-HT) and angiotensin II (AngII) in the bypass graft spasm, we examined the contractile reactivity to 5-HT or AngII of isolated human endothelium-denuded saphenous vein (SV) harvested from DM and non-DM patients. The 5-HT-induced constriction of the SV was significantly augmented in the DM group than in the non-DM group, which is similar to our previous report. AngII-induced constriction of the SV was also significantly augmented in the DM group than the non-DM group. Especially in the non-DM group, the AngII-induced maximal vasoconstriction was markedly lower than the 5-HT-induced one. Meanwhile, the increasing rates of AngII-induced vasoconstriction in the DM group to the non-DM group were significantly greater than those of 5-HT-induced vasoconstriction. These results indicate that 5-HT is a potent inducer of SV graft spasm in both DM and non-DM patients, while AngII is a potent inducer of SV graft spasm only in patients with DM. Furthermore, the protein level of AngII AT₁ receptor (AT₁R), but not the protein level of 5-HT_2A receptor, in the membrane fraction of the SV smooth muscle cells of DM patients was significantly increased as compared with that of the non-DM patients. These results suggest that the mechanism for hyperreactivity to AngII in the SV from DM patients is due to, at least in part, the increase in the amount of AT₁R on membrane of the SV smooth muscle cells.     

Coronary Atherosclerotic Plaque Detected by Computed Tomographic Angiography in Subjects with Diabetes Compared to Those without Diabetes

Objectives

Little data are available regarding coronary plaque composition and semi-quantitative scores in individuals with diabetes; the extent to which diabetes may affect the presence and extent of Coronary Artery Calcium (CAC) needs more evaluation. Considering that this information may be of great value in formulating preventive interventions in this population, we compared these findings in individuals with diabetes to those without.

Methods

Multi-Detector Computed Tomographic (MDCT) images of 861 consecutive patients with diabetes who were referred to Los Angeles Biomedical Research Institute from January 2000 to September 2012, were evaluated using a 15–coronary segment model. All 861 patients underwent calcium scoring and from these; 389 had coronary CT angiography (CTA). CAC score was compared to 861 age, sex and ethnicity matched controls without diabetes after adjustment for Body Mass Index (BMI), family history of coronary artery disease, hyperlipidemia, hypertension and smoking. Segment Involvement Score (SIS; the total number of segments with any plaque), Segment Stenosis Score (SSS; the sum of maximal stenosis score per segment), Total Plaque Score (TPS; the sum of the plaque amount per segment) and plaque compositionwere compared to 389 age, sex and ethnicity matched controls without diabetes after adjustment for BMI, family history of coronary artery disease, hyperlipidemia, hypertension and smoking.

Results

Diabetes was positively correlated to the presence and extent of CAC (P<0.0001 for both). SIS, SSS and TPS were significantly higher in those with diabetes (P<0.0001). Number of mixed and calcified plaques were significantly higher in those with diabetes (P = 0.018 and P<0.001 respectively) but there was no significant difference in the number of non-calcified plaques between the two groups (P = 0.398).

Conclusions

Patients with diabetes have higher CAC and semi-quantitative coronary plaque scores compared to the age, gender and ethnicity matched controls without diabetes after adjustment for cardiovascular risk factors. Since mixed plaque is associated with worse long-term clinical outcomes, these findings support more aggressive preventive measures in this population.     

Improvement of Image Quality and Diagnostic Performance by an Innovative Motion-Correction Algorithm for Prospectively ECG Triggered Coronary CT Angiography

Objective

To investigate the effect of a novel motion-correction algorithm (Snap-short Freeze, SSF) on image quality and diagnostic accuracy in patients undergoing prospectively ECG-triggered CCTA without administering rate-lowering medications.

Materials and Methods

Forty-six consecutive patients suspected of CAD prospectively underwent CCTA using prospective ECG-triggering without rate control and invasive coronary angiography (ICA). Image quality, interpretability, and diagnostic performance of SSF were compared with conventional multisegment reconstruction without SSF, using ICA as the reference standard.

Results

All subjects (35 men, 57.6 ± 8.9 years) successfully underwent ICA and CCTA. Mean heart rate was 68.8±8.4 (range: 50–88 beats/min) beats/min without rate controlling medications during CT scanning. Overall median image quality score (graded 1–4) was significantly increased from 3.0 to 4.0 by the new algorithm in comparison to conventional reconstruction. Overall interpretability was significantly improved, with a significant reduction in the number of non-diagnostic segments (690 of 694, 99.4% vs 659 of 694, 94.9%; P<0.001). However, only the right coronary artery (RCA) showed a statistically significant difference (45 of 46, 97.8% vs 35 of 46, 76.1%; P = 0.004) on a per-vessel basis in this regard. Diagnostic accuracy for detecting ≥50% stenosis was improved using the motion-correction algorithm on per-vessel [96.2% (177/184) vs 87.0% (160/184); P = 0.002] and per-segment [96.1% (667/694) vs 86.6% (601/694); P <0.001] levels, but there was not a statistically significant improvement on a per-patient level [97.8 (45/46) vs 89.1 (41/46); P = 0.203]. By artery analysis, diagnostic accuracy was improved only for the RCA [97.8% (45/46) vs 78.3% (36/46); P = 0.007].

Conclusion

The intracycle motion correction algorithm significantly improved image quality and diagnostic interpretability in patients undergoing CCTA with prospective ECG triggering and no rate control.     

Disease-Specific Mortality and Secondary Primary Cancer in Well-Differentiated Thyroid Cancer with Type 2 Diabetes Mellitus

Background

Increased body mass index is related to the incidence of thyroid cancer. However, the presentation and therapeutic outcomes of different thyroid cancers and type 2 diabetes mellitus (DM) have not been studied. This study investigated the effect of type 2 DM on the clinical presentations and therapeutic outcome of well-differentiated thyroid cancer.

Methods and Findings

A retrospective analysis of adult thyroid cancer patients with or without type 2 DM admitted between January 2001 and December 2010 was performed at an institution. A total of 1,687 well-differentiated thyroid cancer patients with different histological patterns were enrolled. Among these subjects, 122 were type 2 DM patients. Patients with thyroid cancer and type 2 DM were significantly older than non-DM patients. After a mean follow-up period of 5.6±0.1 years, patients with thyroid cancer and type 2 DM showed a higher percentage of disease progression than non-DM patients (24.6% vs. 17.4%). In addition, disease-specific mortality was higher in the type 2 DM group (10.7% vs. 3.8%). Thyroid cancer patients with type 2 DM showed a higher percentage of secondary primary cancers than those without DM (10.7% vs. 4.9%). Thyroid cancer-specific survival rates in the type 2 DM and non-DM groups were 82.2% and 94.9% at 5 years, 72.9% and 91.4% at 10 years, and 36.5% and 61.3% at 20 years, respectively. Multivariate analysis showed that type 2 DM was independent of thyroid cancer-specific mortality.

Conclusion

Patients with type 2 DM and well-differentiated thyroid cancer had an advanced tumor-node-metastasis stage at the time of diagnosis and an increased disease-specific mortality. Aggressive surgical procedures and close follow-up for well-differentiated thyroid cancer patients with type 2 DM are therefore necessary.     

Novel human sex-typing strategies based on the autism candidate gene NLGN4X and its male-specific gametologue NLGN4Y

The male predominance in the incidence of nasopharyngeal carcinoma (NPC) suggests the contribution of the X chromosome to the susceptibility of NPC. However, no X-linked susceptibility loci have been examined by genome-wide association studies (GWASs) for NPC by far. To understand the contribution of the X chromosome in NPC susceptibility, we conducted an X chromosome-wide association analysis on 1615 NPC patients and 1025 healthy controls of Guangdong Chinese, followed by two validation analyses in Taiwan Chinese (n = 562) and Malaysian Chinese (n = 716). Firstly, the proportion of variance of X-linked loci over phenotypic variance was estimated in the discovery samples, which revealed that the phenotypic variance explained by X chromosome polymorphisms was estimated to be 12.63% (non-dosage compensation model) in males, as compared with 0.0001% in females. This suggested that the contribution of X chromosome to the genetic variance of NPC should not be neglected. Secondly, association analysis revealed that rs5927056 in DMD gene achieved X chromosome-wide association significance in the discovery sample (OR = 0.81, 95% CI 0.73–0.89, P = 1.49 × 10−5). Combined analysis revealed rs5927056 for DMD gene with suggestive significance (P = 9.44 × 10−5). Moreover, the female-specific association of rs5933886 in ARHGAP6 gene (OR = 0.62, 95%CI: 0.47–0.81, P = 4.37 × 10−4) was successfully replicated in Taiwan Chinese (P = 1.64 × 10−2). rs5933886 also showed nominally significant gender × SNP interaction in both Guangdong (P = 6.25 × 10−4) and Taiwan datasets (P = 2.99 × 10−2). Our finding reveals new susceptibility loci at the X chromosome conferring risk of NPC and supports the value of including the X chromosome in large-scale association studies.     

高血压患者血压控制水平、血脂水平及颈动脉斑块与冠脉病变的关系

目的:探讨血压控制水平、血脂水平和颈动脉斑块与高血压患者冠脉病变程度和病变支数的关系。方法:回顾性分析2014年01月至2016年05月收住于南京中医药大学附属江苏省中西医结合医院心血管科的原发性高血压患者273例,按血压控制水平分为达标组和未达标组。按颈动脉超声结果判断有无斑块,冠状动脉造影结果使用Gensini评分和病变支数表示,并检测血脂指标。结果:血压控制达标者130人(47.61%),颈动脉有斑块者193例(70.70%)。与血压控制达标患者相比,血压控制不达标者冠脉病变支数及冠脉狭窄程度得分均明显增加(P0.05)。血压不达标合并斑块患者冠脉病变支数和狭窄程度与血压达标无斑块、血压达标合并斑块及血压不达标无斑块患者相比均明显增加(P0.001)。患者HDL-C水平与冠状动脉狭窄程度呈负相关(r=-0.139,P=0.022),AI与冠状动脉狭窄程度呈正相关(r=0.136,P=0.025),LDL/HDL-C和AI与冠脉病变支数均呈正相关,分别为(r=0.128,P=0.035)和(r=0.137,P=0.023)。结论:血压控制不佳,高血脂和颈动脉斑块形成可增加高血压患者冠脉病变的严重程度。     

Effect of tailored use of tirofiban in patients with Non-ST-elevation acute coronary syndrome undergoing percutaneous coronary intervention: a randomized controlled trial

The association of sodium intake with the risk of cardiovascular morbidity and mortality is inconsistent. Thus, the present meta-analysis was conducted to summarize the strength of association between sodium intake and cardiovascular morbidity and mortality. PubMed, Embase, and the Cochrane Library were searched systematically to identify the relevant studies up to October 2017. The effect estimates for 100 mmol/day increase in sodium intake were calculated using 95% confidence intervals (CIs) of cardiac death, total mortality, stroke, or stroke mortality for low (< 3 g/d), moderate (3–5 g/d), or heavy (> 5 g/d) sodium intake, and minimal sodium intake comparison. A total of 16 prospective cohort studies reported data on 205,575 individuals. The results suggested that an increase in sodium intake by 100 mmol/d demonstrated little or no effect on the risk of cardiac death (P = 0.718) and total mortality (P = 0.720). However, the risk of stroke incidence (P = 0.029) and stroke mortality (P = 0.007) was increased significantly by 100 mmol/day increment of sodium intake. Furthermore, low sodium intake was associated with an increased risk of cardiac death (P = 0.003), while moderate (P < 0.001) or heavy (P = 0.001) sodium intake was associated with an increased risk of stroke mortality. These findings suggested that sodium intake by 100 mmol/d increment was associated with an increased risk of stroke incidence and stroke mortality. Furthermore, low sodium intake was related to an increased cardiac death risk, while moderate or heavy sodium intake was related to an increased risk of stroke mortality.     

Relationship among coronary plaque compliance, coronary risk factors and tissue characteristics evaluated by integrated backscatter intravascular ultrasound

ABSTRACT: BACKGROUND: The purpose of the present study was to evaluate the mechanical properties of coronary plaques and plaque behavior, and to elucidate the relationship among tissue characteristics of coronary plaques, mechanical properties and coronary risk factors using integrated backscatter intravascular ultrasound (IB-IVUS). Methods: Non-targeted plaques with moderate stenosis (plaque burden at the minimal lumen site: 50-70%) located proximal to the site of the percutaneous coronary intervention target lesions were evaluated by IB-IVUS. Thirty-six plaques (less calcified group: an arc of calcification [less than or equal to]10) in 36 patients and 22 plaques (moderately calcified group: 10< an arc of calcification [less than or equal to]60) in 22 patients were evaluated. External elastic membrane volume (EEMV) compliance, lumen volume (LV) compliance, plaque volume (PV) response (difference between PV in systole and diastole), EEM area stiffness index were measured at the minimal lumen site. Relative lipid volume (lipid volume/internal elastic membrane volume) was calculated by IB-IVUS. Results: In the less calcified group, there was a significant correlation between EEMV compliance and the relative lipid volume (r=0.456, p=0.005). There was a significant inverse correlation between EEM area stiffness index and the relative lipid volume (p=0.032, r =-0.358). The LV compliance and EEM area stiffness index were significantly different in the diabetes mellitus (DM) group than in the non-DM group (1.32 +/- 1.49 vs. 2.47 +/- 1.79 %/10 mmHg, p =0.014 and 28.3 +/- 26.0 vs. 15.7 +/- 17.2, p =0.020). The EEMV compliance and EEM area stiffness index were significantly different in the hypertension (HTN) group than in the non-HTN group (0.77 +/- 0.68 vs. 1.57 +/- 0.95 %/10 mmHg, p =0.012 and 26.5 +/- 24.3 vs. 13.0 +/- 16.7, p =0.020). These relationships were not seen in the moderately calcified group. Conclusion: The present study provided new findings that there was a significant correlation between mechanical properties and tissue characteristics of coronary arteries. In addition, our results suggested that the EEMV compliance and the LV compliance were independent and the compliance was significantly impaired in the patients with DM and/or HTN. Assessment of coronary mechanical properties during PCI may provide us with useful information regarding the risk stratification of patients with coronary heart disease.     

Pericardial fat amount is an independent risk factor of coronary artery stenosis assessed by multidetector-row computed tomography: the Korean Atherosclerosis Study 2

Pericardial fat surrounding the heart and coronary arteries might aggravate vessel wall inflammation and stimulate the progression of coronary atherosclerosis. However, there has been little comprehensive evaluation of the effects of pericardial fat on coronary artery disease (CAD). We investigated the relationship between pericardial fat volume and the severity of coronary artery stenosis assessed by computed tomography and angiography among patients with suspected CAD. Participants from the cohort of the Korean Atherosclerosis Study 2 (n = 402, mean age of 54 years, 57.0% men) underwent 64-slice multidetector-row computed tomography (MDCT) to assess pericardial fat amount, coronary artery calcium score (CACS), severity of coronary artery stenosis, and plaque characteristics. Patients with atherosclerotic lesion had significantly larger volume of pericardial fat than patients without atherosclerosis (308 ± 96 cm(3) vs. 251 ± 93 cm(3); P < 0.01). In a multivariate regression analysis adjusting for age, gender and BMI, subjects with more pericardial fat had a higher risk for significant (>50%) stenosed coronary vessels (odds ratio (OR) = 1.012; 95% confidence interval (CI) 1.001-1.030; P = 0.017). This association remained after adjusting for hypertension, diabetes, smoking status, and lipid profiles (OR = 1.007; 95% CI 1.001-1.014; P = 0.042). In conclusion, an increased pericardial fat volume was an independent risk factor for stenotic CAD and could be helpful in assessing subclinical CADs.     

CXCL4 Plasma Levels Are Not Associated with the Extent of Coronary Artery Disease or with Coronary Plaque Morphology

Background

CXCL4 is a platelet chemokine released at micromolar concentrations upon platelet activation. CXCL4 has been shown to promote atherogenesis by various mechanisms. However, data on CXCL4 plasma levels in patients with coronary artery disease are largely inconclusive. Computed coronary artery angiography (CCTA) represents an excellent tool to quantify and characterize coronary atherosclerotic plaques. We hypothesized that increased CXCL4 plasma levels may be associated with features of plaque instability resulting in adverse cardiovascular events. Specifically, we sought to determine whether CXCL4 levels are correlated with specific features of coronary artery disease including (1) plaque volume, (2) calcium score, (3) degree of stenosis, or (4) vascular remodeling.

Methods and Results

CXCL4 plasma levels were measured by ELISA in 217 patients undergoing CCTA for suspected CAD (mean age 64.2 ± 9.4 years, 107 (49.3%) male). Mean CXCL4 plasma levels were 12.5 ± 4.6 ng/mL. There was no significant correlation between CXCL4 levels and any clinical or demographic parameters including cardiovascular risk factors. CXCL4 plasma levels did not differ between patient with or without coronary artery disease (CAD: 12.5 ± 4.5 ng/ml, no CAD: 12.5 ± 4.8 ng/ml). Neither univariate nor multivariate analysis showed an association between CXCL4 levels and plaque volume, total calcium score, degree of stenosis, or vascular remodeling. Subgroup analysis of patients with CAD as confirmed by CCTA did not show any association of CXCL4 levels with the extent of CAD.

Conclusions

While CXCL4 may be present and active within the arterial wall, local increase of CXCL4 may not translate into systemically elevated CXCL4 levels. Further studies will have to test whether CXCL4 may still represent a suitable therapeutic target in human atherosclerosis.     

Association between cardiovascular disease and a history of cancer in patients with chest pain on the fast track outpatient clinic

Background

The purpose of this study is to investigate the prevalence of a history of malignancy in patients with chest pain who were referred for computed tomography angiography as well as the long-term survival and cardiovascular outcomes, including coronary artery disease (CAD) and coronary artery calcium (CAC) percentiles of cancer survivors. These data are relevant since it is unknown how cancer survivors, who underwent cardio-toxic therapies, should be monitored.

Methods

We analysed all patients with chest pain, who came to the outpatient clinic and underwent computed tomography angiography. The primary study endpoint was long-term survival. The secondary endpoints included CAD on computed tomography angiogram (CTA), CAC percentiles, suspected and confirmed malignancy on CTA, and other accidental findings on CTA.

Results

Of all 1,892 patients included in the analyses, 133 (7%) had a history of malignancy and 1,759 (93%) did not. Mortality rates were higher for the cancer survivors (6.5% vs 20.9% after ten years, p < 0.001). The multivariable Cox regression model also showed higher mortality for cancer survivors after ten years (adjusted hazard ratio 2.48 [95% confidence interval: 1.58–3.90]). CAD did not differ between both groups. CAC percentiles were higher in cancer survivors (p = 0.037). Cancer survivors had more suspected malignancies (3.8% vs 0.5%; p = 0.001) and also more confirmed malignancies on CTA (3.0% vs 0.1%; p < 0.001).

Conclusions

Cancer survivors have higher mortality rates, no difference in CAD on CTA, higher CAC percentiles and more often malignancy on CTA compared with patients without a cancer history.

     

Intravascular ultrasound imaging of myocardial-infarction-related arteries after percutaneous transluminal coronary angioplasty reveals significant plaque burden and compensatory enlargement

We studied patients with acute myocardial infarction (MI) by intravascular ultrasound (IVUS) to elucidate the controversy as to the amount and severity of the atherosclerotic disease at the culprit lesion site in acute MI, as discrepancies exist between angiographic and pathological reports. Twenty-five consecutive patients (age 56 3 10.5 years), with acute MI, underwent IVUS study of the MI-related artery immediately following successful PTCA to the culprit lesion. The IVUS images were analyzed quantitatively and qualitatively and were compared with the angiography of the same arteries. At the PTCA site, 64% of the lesions had an area stenosis of 50-70% and the plaque cross-sectional area (CSA) averaged 0.5 3 0.18 of the arterial CSA. IVUS-defined atherosclerosis was found also in 72% of the segments proximal and distal to the culprit lesion with a plaque/artery CSA ratio of 0.25 3 0.2. The angiogram revealed only 30% of these segments to be abnormal (P 3 0.001). Sixty-nine per cent of all the plaques were defined as 'soft' (low echo-genecity) versus 31% 'hard' (high echo-genecity). The hard plaques were larger than the soft plaques (0.5 3 1.6 versus 0.37 3 0.19 CSA index, respectively, P 3 0.01). With the increase in plaque area there was a significant increase in arterial cross-sectional area. This was demonstrated for all the diseased segments with a correlation coefficient of 0.49 (P 3 0.0001) and for the diseased reference sites a similar correlation coefficient of 0.49 (P 3 0.003) was found. Contrary to coronary angiographic-based reports, this IVUS study revealed a significant atheromatous plaque burden at the culprit lesion of MI-related arteries as well as diffuse atherosclerosis in the reference segments proximal and distal to the lesion. The detection of compensatory enlargement may explain the discrepancies between the histopathological and the angiographic studies.     

Low dose computerized tomography examinations of coronary occlusive disease

Background: The aim of this study was to present an original technique of low-dose coronary computerized tomographyangiography (CCTA) for the evaluation and early diagnosis of coronary occlusive disease (COD) and to compare from this technique of CCTA with those resulting from the latest conventional angiography and multidetector computerized tomography units. Methodology: The study included 820 CCTA exams of patients with COD (average age 61 +/? 7 years), with a follow-up exam in 204 male (39%) and 62 female (20%) patients with hemodynamically insignificant coronary occlusion. Exams were performed using a 64-slice computerized tomography (CT) unit using electrocardiography (ECG)-triggering and individual settings (voltage of the x-ray tube and effective tube-current) based on each patient’s body mass index. Exponential dose for each exam was defined. Results:There was a statistically significant progression in the number of patients in whom occlusion of one of 3 coronary arteries occurred in hemodynamically significant occlusive disease (occlusion of more than 50% of lumen) — 60 of 204 males and 12 of 62 females (p<0.0001 and p<0.001). The mid-effective radiation dose during CCTA exams was 1.9+/-0.7mSv (range of 0.9 to 3.9 mSv). Conclusion: Prospective ECG-triggering allowed for low-dose CCTA exams while still enabling high diagnostic accuracy in evaluating patients with COD. The technique used in this study resulted in 2 times less the exponential dose than conventional angiography.     

Independent prognostic value of coronary artery calcium score and coronary computed tomography angiography in an outpatient cohort of low to intermediate risk chest pain patients

Background

Limited studies report on the additional prognostic value of coronary computed tomography angiography (CCTA) and the coronary artery calcium score (CACS).

Methods

For a median of 637 days, 1551 outpatients with chest pain, without known coronary artery disease (CAD) and low or intermediate pre-test probability of CAD, were followed for major adverse cardiac events (MACE), defined as death, myocardial infarction or late revascularisation. Cox proportional hazard regression was used to evaluate the independent prognostic value of CCTA and CACS.

Results

MACE occurred in 23 patients (1.5?%): death (3, 0.2?%), myocardial infarction (4, 0.3?%) and late revascularisation (16, 1.3?%). Multivariate analysis showed an independent prognostic value of CCTA (p?<?0.001), CACS of 100–400 (p?=?0.035) and CACS of >?400 (p?=?0.021). CCTA showed obstructive CAD in 3.1?% of patients with CACS?=?0. No events occurred in patients with CACS?=?0 without obstructive CAD at CCTA, whereas 2/23 patients (9?%) with CACS?=?0 with obstructive CAD had a MACE.

Conclusions

Our study shows that both CCTA and higher CACS categories have independent prognostic value in chest pain patients with low to intermediate pre-test probability of obstructive CAD, in which CCTA is appropriate. Furthermore a non-negligible amount of patients with CACS?=?0 have obstructive CAD at CCTA. CCTA can be used in these patients to identify those at risk for MACE.