Quantitative assessment of tissue prolapse on optical coherence tomography and its relation to underlying plaque morphologies and clinical outcome in patients with elective stent implantation

Background

Tissue prolapse (TP) is sometimes observed after percutaneous coronary intervention (PCI), but its clinical significance remains unclear. We investigated the relationship between TP volume on optical coherence tomography (OCT) after PCI and underlying plaque morphologies and the impact of TP on clinical outcomes.

Methods

We investigated 178 native coronary lesions with normal pre-PCI creatine kinase-myocardial band (CK-MB) values (154 lesions with stable angina; 24 with unstable angina). TP was defined as tissue extrusion from stent struts throughout the stented segments. All lesions were divided into tertiles according to TP volume. The differences in plaque morphologies and 9-month clinical outcomes were evaluated.

Results

TP volume was correlated with lipid arc (r = 0.374, p < 0.0001) and fibrous cap thickness (r = − 0.254, p = 0.001) at the culprit sites. The frequency of thin-cap fibroatheroma (TCFA) was higher in the largest TP tertile (≥ 1.38 mm³) (p = 0.015). In multivariate analysis, right coronary artery lesion (odds ratio [OR]: 2.779; p = 0.005), lesion length (OR: 1.047; p = 0.003), and TCFA (OR: 2.430; p = 0.022) were related to the largest TP tertile. Lesions with post-PCI CK-MB elevation (> upper reference limit) had larger TP volume than those without (1.28 [0.48 to 3.97] vs. 0.70 [0.16 to 1.64] mm³, p = 0.007). The prevalence of cardiac events during the 9-month follow-up was not significantly different according to TP volume.

Conclusions

TP volume on OCT was related to plaque morphologies and instability, and post-PCI myocardial injury, but not to worse 9-month outcomes.     

Comparing coronary artery calcium among U.S. South Asians with four racial/ethnic groups: The MASALA and MESA studies

Objectives

South Asians (individuals from India, Pakistan, Bangladesh, Nepal, and Sri Lanka) have high rates of cardiovascular disease which cannot be explained by traditional risk factors. Few studies have examined coronary artery calcium (CAC) in South Asians.

Methods

We created a community-based cohort of South Asians in the United States and compared the prevalence and distribution of CAC to four racial/ethnic groups in the Multi-Ethnic Study of Atherosclerosis (MESA). We compared 803 asymptomatic South Asians free of cardiovascular disease to the four MESA racial/ethnic groups (2622 Whites, 1893 African Americans, 1496 Latinos and 803 Chinese Americans).

Results

The age-adjusted prevalence of any CAC was similar between White and South Asian men, but was lower in South Asian women compared to White women. After adjusting for all covariates associated with CAC, South Asian men were similar to White men and had higher CAC scores compared to African Americans, Latinos and Chinese Americans. In fully adjusted models, CAC scores were similar for South Asian women compared to all women enrolled in MESA. However, South Asian women ≥70 years had a higher prevalence of any CAC than most other racial/ethnic groups.

Conclusions

South Asian men have similarly high CAC burden as White men, but higher CAC than other racial/ethnic groups. South Asian women appear to have similar CAC burden compared to other women, but have somewhat higher CAC burden in older age. The high burden of subclinical coronary atherosclerosis in South Asians may partly explain higher rates of cardiovascular disease in South Asians.     

Aged garlic extract with supplement is associated with increase in brown adipose,decrease in white adipose tissue and predict lack of progression in coronary atherosclerosis

Background

Aged garlic extract with supplement (AGE-S) significantly reduces coronary artery calcium (CAC). We evaluated the effects of AGE-S on change in white (wEAT) and brown (bEAT) epicardial adipose tissue, homocysteine and CAC.

Methods

Sixty subjects, randomized to a daily capsule of placebo vs. AGE-S inclusive of aged garlic-extract (250 mg) plus vitamin-B12 (100 μg), folic-acid (300 μg), vitamin-B6 (12.5 mg) and l-arginine (100 mg) underwent CAC, wEAT and bEAT measurements at baseline and 12 months. The postcuff deflation temperature-rebound index of vascular function was assessed using a reactive-hyperemia procedure. Vascular dysfunction was defined according to the tertiles of temperature-rebound at 1 year of follow-up. CAC progression was defined as an annual-increase in CAC > 15%.

Results

From baseline to 12 months, there was a strong correlation between increase in wEAT and CAC (r² = 0.54, p = 0.0001). At 1 year, the risks of CAC progression and increased wEAT and homocysteine were significantly lower in AGE-S to placebo (p < 0.05). Similarly, bEAT and temperature-rebound were significantly higher in AGE-S as compared to placebo (p < 0.05). Strong association between increase in temperature-rebound and bEAT/wEAT ratio (r² = 0.80, p = 0.001) was noted, which was more robust in AGE-S. Maximum beneficial effect of AGE-S was noted with increase in bEAT/wEAT ratio, temperature-rebound, and lack of progression of homocysteine and CAC.

Conclusions

AGE-S is associated with increase in bEAT/wEAT ratio, reduction of homocysteine and lack of progression of CAC. Increases in bEAT/wEAT ratio correlated strongly with increases in vascular function measured by temperature-rebound and predicted a lack of CAC progression and plaque stabilization in response to AGE-S.     

Comparison of insulin sensitivity measures in South Asians

Objective

South Asians have increased visceral adiposity, insulin resistance and greater prevalence of type 2 diabetes and cardiovascular disease when compared to Caucasians of European origin. Surrogate markers of insulin resistance such as the composite insulin sensitivity (Matsuda) index correlate with glucose clamps in other populations, but ethnicity can affect these indices. We compared the Matsuda index, homeostasis model assessment (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and triglyceride/HDL ratio to insulin sensitivity derived from euglycemic clamps in healthy South Asians and Caucasians.

Materials/Methods

Twenty-three healthy South Asians and 18 Caucasians matched for age (mean ± SE = 33.6 ± 2.1 vs. 36.0 ± 3.0 years) and BMI (25.2 ± 1.1 vs. 24.6 ± 0.9 kg/m²) underwent 75 g oral glucose tolerance test (OGTT), 2-h euglycemic hyperinsulinemic clamp (240 pmol · m^− 2 · min^− 1), fasting lipid profile, and anthropometric measures.

Results

South Asians had higher fasting insulin (41 ± 5 vs. 21 ± 2 pmol/l; p = 0.002) and lower HDL-C (1.25 ± 0.06 vs. 1.56 ± 0.10 mmol/l; p = 0.010), but similar fasting glucose (5.0 ± 0.1 vs. 4.9 ± 0.1 mmol/l) levels vs. Caucasians. South Asians had significantly decreased measures of insulin sensitivity derived from both the euglycemic clamp (24.9 ± 1.3 vs. 41.4 ± 1.9 μmol · kg^− 1 · min^− 1; p < 0.0001) and OGTT (Matsuda Index 7.60 ± 0.99 vs. 13.60 ± 1.79; p = 0.004). The Matsuda index correlated highly with clamp insulin sensitivity in South Asians (r = 0.50; p = 0.014) and Caucasians (r = 0.47; p = 0.046). HOMA-IR, QUICKI, and triglyceride/HDL ratio correlated with clamp values in South Asians, but not in Caucasians.

Conclusions

In South Asians, Matsuda index, HOMA-IR, QUICKI, and triglyceride/HDL ratio offer simple and valid surrogate measures of insulin sensitivity that can be employed in larger clinical or epidemiological studies in this ethnic group.     

Coronary artery calcification correlates with the presence and severity of valve calcification

Aim

To investigate the prevalence of coronary artery calcification (CAC) in symptomatic individuals with CT evidence for left heart valve calcification, aortic valve (AVC), mitral valve (MAC) or both.

Methods

This is a retrospective study of 282 consecutive patients with calcification in either the aortic valve or mitral annulus. Calcium scoring of the coronary artery, aortic and mitral valve was measured using the Agatston score.

Results

AVC was more prevalent than MAC (64% vs. 2.5%, p < 0.001), with 34% having both. Absence of CAC was noted in 12.7% of the study population. AVC + CAC were observed in 53.5%, MAC and CAC in 2.1%, and combined AVC, MAC and CAC in 31.6%. The median CAC score was higher in individuals with combined AVC + MAC, followed by those with AVC and lowest was in the MAC group. The majority (40%) of individuals with AVC had CAC score > 400, and only in 16% had CAC = 0. The same pattern was more evident in individuals with AVC + MAC, where 70% had CAC score > 400 and only 6% had CAC score of 0. These results were irrespective of gender. There was no correlation between AVC and MAC but there was modest correlation between CAC score and AVC score (r = 0.28, p = 0.0001), MAC (r = 0.36, p = 0.0001) and with combined AVC + MAC (r = 0.5, p = 0.0001). AVC score of 262 had a sensitivity of 78% and specificity of 92% for the prediction of presence of CAC.

Conclusion

The presence and extent of calcification in the aortic valve or/and mitral valves are associated with severe coronary artery calcification.     

Impact of epicardial fat volume on coronary artery disease in symptomatic patients with a zero calcium score

Background

This study sought to evaluate the prevalence of coronary artery disease (CAD) and the impact of epicardial fat volume (EFV) on CAD in symptomatic patients with a zero calcium score (CS) using multislice computed tomography (MSCT).

Methods

In this study, 1308 consecutive symptomatic patients who underwent 64-slice MSCT with a zero CS were evaluated. EFV was quantified with CS data sets. Presence of an obstructive plaque (diameter stenosis > 50%) and a CT-derived vulnerable plaque, which was defined as a plaque with remodeling index > 1.10 and mean CT density value < 30 HU, was assessed with a CT coronary angiography.

Results

Obstructive plaques were detected in 86 patients (7%) and CT-derived vulnerable plaques in 63 (5%). EFV was larger in patients with obstructive plaques than no plaque (124.3 ± 43.2 cm³ vs. 95.1 ± 40.3 cm³; p < 0.01). Patients with CT-derived vulnerable plaques had a greater amount of EFV than no plaque (133.0 ± 40.2 cm³ vs. 95.1 ± 40.3 cm³; p < 0.01). Multivariate analysis revealed EFV as a predictor of the presence of an obstructive and a CT-derived vulnerable plaque (per 10 cm³; Odds ratio (OR) 1.10; 95% confidence interval (CI), 1.04-1.16; p < 0.01 and OR 1.19; 95% CI, 1.12-1.27; p < 0.01). The combination of EFV and Framingham risk score (FRS) resulted in an area under the receiver-operating characteristic curve for prediction of obstructive and CT-derived vulnerable plaque of 0.75 and 0.75, which was significantly higher than 0.68 and 0.64 for FRS alone (p = 0.02 and p < 0.01).

Conclusions

A zero CS doesn't exclude CAD and EFV can be a useful marker of CAD in symptomatic zero CS patients.     

Synergistic effect of local endothelial shear stress and systemic hypercholesterolemia on coronary atherosclerotic plaque progression and composition in pigs

Background

Systemic risk factors and local hemodynamic factors both contribute to coronary atherosclerosis, but their possibly synergistic inter-relationship remains unknown. The purpose of this natural history study was to investigate the combined in-vivo effect of varying levels of systemic hypercholesterolemia and local endothelial shear stress (ESS) on subsequent plaque progression and histological composition.

Methods

Diabetic, hyperlipidemic swine with higher systemic total cholesterol (TC) (n = 4) and relatively lower TC levels (n = 5) underwent three-vessel intravascular ultrasound (IVUS) at 3–5 consecutive time-points in-vivo. ESS was calculated serially using computational fluid dynamics. 3-D reconstructed coronary arteries were divided into 3 mm-long segments (n = 595), which were stratified according to higher vs. relatively lower TC and low (< 1.2 Pa) vs. higher local ESS (≥ 1.2 Pa). Arteries were harvested at 9 months, and a subset of segments (n = 114) underwent histopathologic analyses.

Results

Change of plaque volume (ΔPV) by IVUS over time was most pronounced in low-ESS segments from higher-TC animals. Notably, higher-ESS segments from higher-TC animals had greater ΔPV compared to low-ESS segments from lower-TC animals (p < 0.001). The time-averaged ESS in segments that resulted in significant plaque increased with increasing TC levels (slope: 0.24 Pa/100 mg/dl; r = 0.80; p < 0.01). At follow-up, low-ESS segments from higher-TC animals had the highest mRNA levels of lipoprotein receptors and inflammatory mediators and, consequently, the greatest lipid accumulation and inflammation.

Conclusions

This study redefines the principle concept that “low” ESS promotes coronary plaque growth and vulnerability by demonstrating that: (i.) the pro-atherogenic threshold of low ESS is not uniform, but cholesterol-dependent; and (ii.) the atherogenic effects of local low ESS are amplified, and the athero-protective effects of higher ESS may be outweighed, by increasing cholesterol levels. Intense hypercholesterolemia and very low ESS are synergistic in favoring rapid atheroma progression and high-risk composition.     

Differential impact of five coronary devices on plaque size: Insights from the ABSORB and SPIRIT trials

Background

Coronary plaque size modification, by either local (device) or systemic treatments, has been the target for many years.

Methods

From ABSORB Cohort A (Absorb BVS 1.0), ABSORB Cohort B (Absorb BVS 1.1), SPIRIT FIRST (Multi-Link Vision vs. Xience V) & SPIRIT II (Xience V vs. Taxus), we calculated the total plaque area (vessel minus lumen area – thus it comprises both compartments – the plaque behind struts and the neointima.) changes by IVUS.

Results

A total of 313 patients were included. Comparison-at-6-month follow-up: All devices induced an increase in the total plaque area. The largest increase occurred with Vision and Taxus stents as compared to other devices [Absorb BVS (1.0 and 1.1) and Xience V], (p = 0.0002). Comparison-at-2-year follow-up: Absorb BVS 1.1 had a larger increase from post procedure in total plaque compared to Absorb BVS 1.0, Xience V and Taxus (p = 0.0499). However, in Absorb BVS 1.1 total plaque showed a reduction of 2.2% from 1 to 3 years. Specifically, the total plaque in the sequential cohorts of Absorb BVS 1.1 increased 16.2% from baseline to 2 years (Cohort B1) while at 3 years this increase is only 5% compared to baseline (Cohort B2).

Conclusions

Local devices affect coronary plaque size differently and it depends on the platform (metallic vs. polymeric) and on whether it is a bare — or drug eluting stent. Coronary scaffolds appear to be a promising alternative to metallic stents since they allow plaque regression at long-term follow-up.     

Radial artery intima-media ratio predicts presence of coronary thin-cap fibroatheroma: A frequency domain-optical coherence tomography study

Background

Peripheral arterial disease is a risk factor for cardiac mortality but pathophysiologic mechanisms linking atherosclerosis of peripheral arteries with coronary events in the single patient have not been established.

Method and results

We evaluated by frequency-domain optical coherence tomography (FD-OCT) the possible association between culprit coronary plaque characteristics and proximal radial artery features in a cohort of 51 patients symptomatic coronary artery disease undergoing coronary procedures by transradial route. FD-OCT coronary artery analysis included assessment of TCFA and thrombus. FD-OCT radial artery analysis included intimal thickness index (ITI: intimal area/medial area), intima-media ratio (IMR: the maximum intimal thickness/medial thickness), and percentage of luminal narrowing [%LN: (intimal area + medial area) / external elastic membrane area × 100]. Coronary TCFA and thrombus were detected in 19 (37%) and 7 (14%) patients, respectively. TCFA was significantly associated with higher values of radial artery ITI (0.35 vs. 0.26, p = 0.02) and IMR (0.45 vs. 0.32, p = 0.03), but not with %LN. In contrast, coronary thrombus was only associated with higher %LN (26.7 vs. 22.8, p = 0.02). Multivariate logistic regression analysis identified proximal radial artery IMR (OR 16.3, 95% CI 1.1 to 245.1) as an independent predictor of TCFA.

Conclusions

In patients with symptomatic coronary atherosclerosis, vessel wall modifications at the level of the proximal radial artery are associated with adverse coronary features like TCFA and thrombus.     

Discrepancy of calcium detection between gray scale intravascular ultrasound and spectral analysis of radiofrequency data

Background

We evaluated discrepancy of calcium detection between gray scale intravascular ultrasound (IVUS) and virtual histology (VH)–IVUS and the association between coronary calcium and plaque composition.

Methods

Study population consisted of 162 consecutive patients who underwent percutaneous coronary intervention with VH–IVUS study. Subjects were divided into 3 groups based on gray scale IVUS findings; No calcification group (n = 50), spotty group (n = 56) who had a lesion containing only small calcium deposits within an arc < 90° and diffuse group (n = 56) who had a diffuse calcified lesion with an arc ≥ 90° in ≥ 1 cross-sectional image of the lesion.

Results

No calcification group was younger than spotty and diffuse groups (54.4 ± 13.0 years vs. 61.1 ± 10.7 years and 64.2 ± 9.9 years, p = 0.011 and p < 0.001, respectively). No calcification group had some degree of dense calcium (5. 7 ± 6.9 mm³) by VH–IVUS analysis. Furthermore, calcified volume by VH–IVUS in no calcification group was similar to those in spotty group (5.7 ± 6.9 mm³ vs. 5.4 ± 4.4 mm³). Dense calcium volume was correlated directly with plaque volume (r = 0.65, p < 0.001), fibrous volume (r = 0.54, p < 0.001), fibro-fatty volume (r = 0.29, p < 0.001) and lipid core volume (r = 0.77, p < 0.001). In multiple regression analysis, lipid core volume (β = 0.287, 95% confidence interval (CI) 0.187–0.388, p < 0.001) was an independent predictor of dense calcium volume.

Conclusions

This study showed that coronary calcium can be present even if invisible in gray scale IVUS and associated with lipid core volume, which is a characteristic of plaque vulnerability.     

Prognosis of patients with mild–moderate coronary artery stenosis detected by coronary computed tomography angiography

Background

In addition to the diagnostic performance, coronary computed tomography angiography (CTA) can give important data regarding the prognosis of coronary artery disease (CAD). In this study we aimed to evaluate the prognostic role of coronary CTA in patients with suspected CAD and mild–moderate coronary stenosis.

Methods

A total of 1115 patients (602 male, 54%; age 58.4 ± 11.4) without previous CAD were enrolled. Patients underwent coronary CTA imaging using dual-source 64-slice CT scanner. For categorization of the coronary atherosclerotic plaques (CAP), the coronary system was divided into 16 separate segments. For each segment, CAPs were categorized as: calcified, noncalcified and mixed.

Results

During follow-up of 29.7 ± 13.2 months, cardiovascular events defined as ST segment elevation myocardial infarction (4 patients), non-ST segment elevation myocardial infarction (5 patients) and unstable angina pectoris (20 patients) requiring revascularization or hospital admission were recorded. Cox hazard regression analysis revealed an association between the severity of luminal stenosis (HR: 4.73, 95% CI: 1.36–16.47, p < 0.05) and extent (HR: 1.10, 95% CI: 1.00–1.22, p = 0.051) and the adverse coronary events in the follow-up. Multivariate Cox hazard regression analysis revealed that nonobstructive (≤ 50%) lesions were the only factor causing increased probability of coronary events in the follow-up (HR: 4.77, 95% CI: 1.36–16.74, p < 0.05).

Conclusion

The presence and severity of luminal stenosis shown by coronary CTA were associated with prognosis of coronary events in the follow-up. These results may improve the risk stratification in patients evaluated by coronary CTA and provide strategies for the individualized prevention programs.     

Coronary flow dynamics in children after repair of Tetralogy of Fallot

Objectives

To assess the possible effect of a stiff right ventricle on the coronary flow (CF) in patients with post-operative Tetralogy of Fallot (TOF).

Background

Right ventricular restrictive physiology i.e. forward flow during atrial contraction (RVRP), is characteristic to many patients with post-operative TOF.

Methods

A total of 34 patients with TOF anatomically corrected through transatrial repair were included. Coronary flow parameters were registered with transthoracic Doppler echocardiography from posterior descending (PDCA) and left anterior descending (LAD) coronary arteries in the same patient in 24/34 (71%) patients. Twenty age-matched healthy children were used as controls. Cardiac magnetic resonance (CMR) imaging was used to detect myocardial fibrosis, RV volume, and RVRP.

Results

The mean age at investigation was 10.2 ± 2.8 years. RV end diastolic and end systolic volumes indexed for BSA were larger in patients with RVRP (p = 0.002 and 0.008 respectively). Peak flow velocity in diastole and flow velocity time integral was increased in patients compared to controls. They were increased in the LAD in patients with fibrosis of RV (n = 11) compared to patients without fibrosis (n = 9) (p = 0.01 and 0.047 respectively). LAD coronary flow was especially increased in patients with RVRP (n = 9) as compared with those without (n = 11), (p = 0.006).

Conclusions

Patients at mid-term followup after correction of TOF show increase of coronary flow. This increase is more pronounced in patients with fibrosis and RVRP of the RV.     

“Polarizing” microplegia improves cardiac cycle efficiency after CABG for unstable angina

Background

Myocardial protection during coronary artery bypass grafting (CABG) for unstable angina (UA) still represents a major challenge, ought to the risk for further ischemia/reperfusion injury. Few studies investigate the biochemical, hemodynamic and echocardiographic results of microplegia (Mic) in UA.

Methods

Eighty UA-patients undergoing CABG were randomized to Mic (Mic-Group) or standard 4:1 blood Buckberg-cardioplegia (Buck-Group). Troponin-I and lactate were sampled from coronary sinus at reperfusion (T1), and from peripheral blood preoperatively (T0), at 6 (T2), 12 (T3) and 48 (T4) hours. Cardiac index (CI), indexed systemic vascular resistances (ISVR), Δp/Δt, cardiac cycle efficiency (CCE), and central venous pressure (CVP) were collected preoperatively (T0), and since Intensive Care Unit (ICU)-arrival (T1) to 24 h (T5). Echocardiographic E-wave (E), A-wave (A), E/A, peak early-diastolic TDI-mitral annular-velocity (Ea), and E/Ea investigated the diastolic function and Wall Motion Score Index (WMSI) the systolic function, preoperatively (T0) and at 96 h (T1).

Results

Mic-Group showed lower troponin-I and lactate from coronary sinus (p = .0001 for both) and during the postoperative course (between-groups p = .001 and .0001, respectively). WMSI improved only after Mic (time-p = .001). Higher CI Δp/Δt and CCE (between-groups p = .0001), with comparable CVP and ISVR (p = N.S.) were detected after Mic. Diastolic function improved in both groups, but better after Mic (between-groups p = .003, .001, and .013 for E, E/A, and Ea, respectively). Mic resulted in lower transfusions (p = .006) and hospitalization (p = .002), and a trend towards lower need/duration of inotropes (p = .04 and p = .041, respectively), and ICU-stay (p = .015).

Conclusion

Microplegia attenuates myocardial damage in UA, reduces transfusions, improves postoperative systo-diastolic function, and shortens hospitalization.     

Status of hypertension and coronary stenosis in asymptomatic type 2 diabetic patients: Analysis from Coronary Computed Tomographic Angiography Registry

Background

Limited data exist regarding the prevalence of coronary artery disease (CAD) as well as clinical outcomes in asymptomatic diabetic patients with normotension, controlled hypertension, and uncontrolled hypertension.

Methods

We enrolled 935 consecutive asymptomatic type 2 diabetic patients without known CAD. Coronary computed tomography angiography was used to evaluate the prevalence and severity of CAD. Blood pressure was measured at baseline. Patients were assigned to one of the three groups: normotension (n = 314), controlled hypertension (systolic blood pressure (SBP) < 140 mmHg with treatment, n = 458), or uncontrolled hypertension (SBP ≥ 140 mmHg with or without treatment, n = 163).

Results

Obstructive CAD (≥ 50% stenosis) increased from the prevalence in normotensive patients (33%) to that in patients with controlled (40%) or uncontrolled hypertension (52%) (p = 0.003). The incidence of obstructive CAD in multivessel or left main CAD also increased across the three groups (13%, 21%, 32%, respectively, p < 0.001). A multivariate logistic regression analysis showed that uncontrolled hypertension was an independent predictor of obstructive CAD (adjusted odds ratio, 2.13; 95% confidence interval (CI), 1.42 to 3.21, p < 0.001). During a median follow-up of 3.1 years, uncontrolled hypertension was associated with increased risk of cardiac death or myocardial infarction compared to the risk in normotensive patients (hazard ratio, 6.11; 95% CI, 1.65 to 22.6, p = 0.007).

Conclusion

In asymptomatic type 2 diabetic patients, uncontrolled hypertension was associated with increased risk of CAD and poor clinical outcomes.     

Soluble lectin-like oxidized LDL receptor-1 (sLOX-1) as a valuable diagnostic marker for rupture of thin-cap fibroatheroma: Verification by optical coherence tomography

Background

Relationships between plaque morphology on optical coherence tomography (OCT) and biomarker levels in the patients with acute coronary syndrome (ACS) have not been fully investigated.

Methods

ACS patients (n = 128) were prospectively enrolled and their plasma levels of soluble lectin-like oxidized LDL receptor-1 (sLOX-1), high-sensitivity C-reactive protein (hs-CRP), and high-sensitivity troponin T (hs-TnT) were measured. Another set of 20 patients with stable angina pectoris (SAP) without plaque rupture or erosion served as controls. Among 128 ACS patients, 75 patients underwent OCT procedure to evaluate culprit plaque morphology, and were categorized into two groups; ACS with plaque rupture (ruptured ACS; R-ACS, n = 54) and ACS without plaque rupture (non-ruptured ACS; N-ACS, n = 21).

Results

Levels of sLOX-1 (p < 0.001), hs-CRP (p = 0.048) and hs-TnT (p < 0.001) were significantly higher in R-ACS than SAP. Levels of sLOX-1 were also significantly higher in R-ACS than in N-ACS (p < 0.001); whereas levels of hs-CRP (p = 0.675), as well as those of hs-TnT (p = 0.055), were comparable between R-ACS and N-ACS. Comparison of receiver operating characteristic (ROC) curves among sLOX-1, hs-CRP and hs-TnT to differentiate R-ACS from N-ACS revealed that the area under the curve (AUC) values of sLOX-1, hs-CRP and hs-TnT were 0.782, 0.531 and 0.643, respectively. ROC curves, generated for these biomarkers, to differentiate ACS with thin-cap fibroatheroma (TCFA) from those without demonstrated that the AUC values of sLOX-1, hs-CRP and hs-TnT were 0.718, 0.506 and 0.524, respectively.

Conclusion

sLOX-1, but not hs-CRP or hs-TnT, can differentiate ACS with plaque rupture from those without, and ACS with TCFA from those without.     

Proximal coronary artery intervention: Stent thrombosis,restenosis and death

Background

Percutaneous coronary intervention (PCI) of lesions in the proximal left anterior descending coronary artery (LAD) may confer a worse prognosis compared with the proximal right coronary artery (RCA) and left circumflex coronary artery (LCX).

Methods

From May 2005, to May 2011 we identified all PCIs for proximal, one-vessel coronary artery disease in the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). We evaluated restenosis, stent thrombosis (ST) and mortality in the LAD as compared to the RCA and LCX according to stent type, bare metal (BMS) or drug-eluting stents (DES).

Results

7840 single vessel proximal PCI procedures were identified. Mean follow-up time was 792 days. No differences in restenosis or ST were seen between the LAD and the RCA. The frequency of restenosis and ST was higher in the proximal LAD compared to the proximal LCX (restenosis: hazard ratio (HR) 2.28, confidence interval (CI) 1.56–3.34 p < 0.001; ST: HR 2.32, CI 1.11–4.85 p = 0.024). We found no difference in mortality related to coronary artery. In the proximal LAD, DES implantation was associated with a lower restenosis rate (HR 0.39, CI 0.27–0.55 p < 0.001) and mortality (HR 0.58, CI 0.41–0.82 p = 0.002) compared with BMS. In the proximal RCA and LCX, DES use was not associated with lower frequency of clinical restenosis or mortality.

Conclusions

Following proximal coronary artery intervention restenosis was more frequent in the LAD than in the LCX. Solely in the proximal LAD we found DES use to be associated with a lower risk of restenosis and death weighted against BMS.     

Relationship between fractional flow reserve and residual plaque volume and clinical outcomes after optimal drug-eluting stent implantation: Insight from intravascular ultrasound volumetric analysis

Background

The underlying cause of FFR reduction and prognostic impact of FFR after optimal DES implantation remain unknown. The study aims were to use intravascular ultrasound (IVUS) to investigate the mechanism responsible for reduced fractional flow reserve (FFR) after optimal drug-eluting stent (DES) implantation and to evaluate FFR effect on clinical outcomes after optimal percutaneous coronary intervention with DES.

Methods

Ninety-seven patients treated with optimal DES implantation under IVUS and pullback FFR guidance were followed clinically (median 17.8 months). Post-stenting IVUS examination and pullback FFR recording were performed, and angiographic and IVUS parameters associated with reduced FFR were evaluated. The composite of major adverse cardiac events (MACE), including cardiac death, myocardial infarction, stent thrombosis, and target vessel revascularization, was analyzed.

Results

Regression analysis showed inverse correlations between post-stent FFR and residual plaque volume index (r = − 0.40, p < 0.01) and residual percent plaque volume (r = − 0.68, p < 0.01) in IVUS but no correlation of minimal lesion diameter with quantitative coronary angiography (r = 0.07, p = 0.50) or IVUS-derived minimal stent area (r = 0.02, p = 0.84). MACE was observed in 10 patients (10.3%), and FFR after optimal stenting was significantly lower in this group (0.86 ± 0.04 vs 0.91 ± 0.04, p < 0.01). The optimal FFR threshold for predicting MACE was 0.90, identified by the receiver operating characteristic curve.

Conclusions

Reduced FFR after optimal DES implantation was associated with residual plaque volume identified by IVUS and future adverse cardiac events.     

Incremental prognostic value of coronary artery calcium score versus CT angiography among symptomatic patients without known coronary artery disease

Objective

To evaluate the prognostic value and test characteristics of coronary artery calcium (CAC) score for the identification of obstructive coronary artery disease (CAD) in comparison with coronary computed tomography angiography (CCTA) among symptomatic patients.

Methods

Retrospective cohort study at two large hospitals, including all symptomatic patients without prior CAD who underwent both CCTA and CAC. Accuracy of CAC for the identification of ≥50% and ≥70% stenosis by CCTA was evaluated. Prognostic value of CAC and CCTA were compared for prediction of major adverse cardiovascular events (MACE, defined as non-fatal myocardial infarction, cardiovascular death, late coronary revascularization (>90 days), and unstable angina requiring hospitalization).

Results

Among 1145 included patients, the mean age was 55 ± 12 years and median follow up 2.4 (IQR: 1.5–3.5) years. Overall, 406 (35%) CCTA were normal, 454 (40%) had <50% stenosis, and 285 (25%) had ≥50% stenosis. The prevalence of ≥70% stenosis was 16%. Among 483 (42%) patients with CAC zero, 395 (82%) had normal CCTA, 81 (17%) <50% stenosis, and 7 (1.5%) ≥ 50% stenosis. 2 (0.4%) patients had ≥70% stenosis. For diagnosis of ≥50% stenosis, CAC had a sensitivity of 98% and specificity of 55%. The negative predictive value (NPV) for CAC was 99% for ≥50% stenosis and 99.6% for ≥70% stenosis by CCTA. There were no adverse events among the 7 patients with zero calcium and ≥50% CAD. For prediction of MACE, the c-statistic for clinical risk factors of 0.62 increased to 0.73 (p < 0.001) with CAC versus 0.77 (p = 0.02) with CCTA.

Conclusion

Among symptomatic patients with CAC zero, a 1–2% prevalence of potentially obstructive CAD occurs, although this finding was not associated with future coronary revascularization or adverse prognosis within 2 years.     

Higher insulin and glucagon-like peptide-1 (GLP-1) levels in healthy,young South Asians as compared to Caucasians during an oral glucose tolerance test

Objective

Higher insulin levels during an oral glucose test (OGTT) have been shown in South Asians. We aimed to investigate if this increased insulin response causes reactive hypoglycemia later on, and if an increased glucagon-like-peptide-1 (GLP-1) response, which could contribute to the hyperinsulinemia, is present in this ethnic group.

Methods

A prolonged, 6-h, 75-g OGTT was performed in healthy, young Caucasian (n = 10) and South Asian (n = 8) men. The glucose, insulin and GLP-1 response was measured and indices of insulin sensitivity and beta-cell activity were calculated.

Results

Age (Caucasians (CAU) 21.5 ± 0.7 years vs South Asians (SA) 21.4 ± 0.7 years (mean ± SEM)) and body mass index (CAU 22.7 ± 0.7 kg/m² vs SA 22.1 ± 0.8 kg/m²) were comparable between the two groups. South Asian men were more insulin resistant, as indicated by a comparable glucose but significantly higher insulin response, and a significantly lower Matsuda index (CAU 8.7(8.6) vs SA 3.2(19.2), median(IQR)). South Asians showed a higher GLP-1 response, as reflected by a higher area under the curve for GLP-1 (CAU 851 ± 99.8 mmol/l vs SA 1235 ± 155.0 mmol/L). During the whole 6-h period, no reactive hypoglycemia was observed.

Conclusion

Healthy, young South Asian men have higher insulin levels during an OGTT as compared to Caucasians. This does not, however, lead to reactive hypoglycemia. The hyperinsulinemia is accompanied by increased levels of GLP-1. Whether this is an adaptive response to facilitate hyperinsulinemia to overcome insulin resistance or reflects a GLP-1 resistant state has yet to be elucidated.     

Combined effects of fibrinogen genetic variability on atherosclerosis in patients with or without stable angina pectoris: Focus on the coagulation cascade and endothelial function

Background

Fibrinogen is a coagulation/inflammatory biomarker strongly associated with atherogenesis. Data have reported that the genetic variability on fibrinogen chains may affect the atherosclerotic process and the risk of coronary artery disease (CAD). We examined the combined effects of the G455A and the G58A fibrinogen genetic polymorphisms on prothrombotic profile, endothelial function and the risk of CAD in a Caucasian population.

Methods

We recruited 422 patients with angiographically documented CAD and 277 controls matched for age and gender. The two polymorphisms were genotyped by polymerase chain reaction and restriction endonuclease digestion. Fibrinogen and D-Dimers levels, as well as factors' (f) V, X activity were measured by standard coagulometry techniques. Endothelial function was assessed by the flow mediated dilatation (FMD) of the brachial artery.

Results

The two polymorphisms had no significant effect on the risk for CAD. Although the 58AA subjects had not significantly different levels of fibrinogen compared with the 58GG + GA in both groups (p = NS), we importantly found that the 455AA homozygosity was associated with increased fibrinogen levels not only in the control group (p = 0.035), but also in the CAD group (p < 0.001) compared to the G allele carriers. Moreover, both the 58AA (p = 0.016) and 455AA homozygotes (p = 0.022) presented with higher levels of D-Dimers in the CAD group. Interestingly, the 455AA homozygotes had increased fV activity in the CAD group (p = 0.048). However, no significant effects were observed on fX activity and FMD.

Conclusions

Both fibrinogen polymorphisms are capable to modify the atherosclerotic process via their effects on the coagulation cascade.