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Journal of the American College of Cardiology | 2010

Intravascular Ultrasound-Derived Measures of Coronary Atherosclerotic Plaque Burden and Clinical Outcome

Stephen J. Nicholls; Amy Hsu; Kathy Wolski; Bo Hu; Ozgur Bayturan; Andrea Lavoie; Kiyoko Uno; E. Murat Tuzcu; Steven E. Nissen

OBJECTIVES The aim of this study was to investigate the relationship between intravascular ultrasound (IVUS)-derived measures of atherosclerosis and cardiovascular outcomes. BACKGROUND IVUS has been used in clinical trials to evaluate the effect of medical therapies on coronary atheroma progression. METHODS Coronary plaque progression was evaluated in 4,137 patients in 6 clinical trials that used serial IVUS. The relationship between baseline and change in percent atheroma volume (PAV) and total atheroma volume with incident major adverse cardiovascular events (MACE) was investigated. RESULTS PAV increased by 0.3% (p < 0.001), and 19.9% of subjects experienced MACE (0.9% death, 1.8% myocardial infarction, 18.9% coronary revascularization). Greater baseline PAVs were observed in patients who experienced myocardial infarctions (42.2 +/- 9.6% vs. 38.6 +/- 9.1%, p = 0.001), coronary revascularization (41.2 +/- 9.3% vs. 38.1 +/- 9.0%, p < 0.001), or MACE (41.3 +/- 9.2% vs. 38.0 +/- 9.0%, p < 0.001). Each standard deviation increase in PAV was associated with a 1.32-fold (95% confidence interval: 1.22 to 1.42; p < 0.001) greater likelihood of experiencing a MACE. During follow-up (21.1 +/- 3.7 months), greater increases in PAV, but not total atheroma volume, were observed in subjects who experienced MACE compared with those who did not (0.95 +/- 0.19% vs. 0.46 +/- 0.16%, p < 0.001). Each standard deviation increase in PAV was associated with a 1.20-fold (95% confidence interval: 1.10 to 1.31; p < 0.001) greater risk for MACE. Multivariate analysis revealed that factors associated with MACE included baseline PAV (p < 0.0001), change in PAV (p = 0.002), smoking (p = 0.0002) and hypertension (p = 0.01). CONCLUSIONS A direct relationship was observed between the burden of coronary atherosclerosis, its progression, and adverse cardiovascular events. The relationship between disease progression and outcomes largely reflected the need for coronary revascularization. These data support the use of atherosclerosis imaging with IVUS in the evaluation of novel antiatherosclerotic therapies.


JAMA Internal Medicine | 2010

The metabolic syndrome, its component risk factors, and progression of coronary atherosclerosis.

Ozgur Bayturan; E. Murat Tuzcu; Andrea Lavoie; Tingfei Hu; Kathy Wolski; Paul Schoenhagen; Samir Kapadia; Steven E. Nissen; Stephen J. Nicholls

BACKGROUND The mechanism that confers adverse cardiovascular prognosis in patients with the metabolic syndrome (MetS) remains unclear. We sought to investigate the association of MetS and its component risk factors with progression of coronary atherosclerosis. METHODS We performed a systematic review of 3459 patients who participated in 7 clinical trials that monitored coronary atheroma progression with intravascular ultrasonography. Patients with or without MetS were compared with regard to clinical characteristics, coronary atheroma burden at baseline, and change on serial evaluation. Relationships between plaque progression (> or =5% increase in percent atheroma volume [PAV]), MetS, and its component risk factors were investigated. RESULTS The metabolic syndrome was highly prevalent and was associated with greater progression of PAV (+0.51% +/- 0.23% vs +0.23% +/- 0.24%; P = .003). Multivariable analysis showed that MetS was associated with a greater likelihood of undergoing progression of PAV (adjusted odds ratio [OR], 1.25; 95% confidence interval [CI], 1.05-1.48; P = .01). When the individual components were used in the model instead of MetS, hypertriglyceridemia (OR, 1.26; 95% CI, 1.06-1.49; P = .008) and a body mass index of 30 or higher (1.18, 1.00-1.40; P = .05) predicted progression of PAV. However, after adjusting for its individual components, MetS was no longer an independent predictor (OR, 1.04; 95% CI, 0.79-1.37; P = .79). CONCLUSION Although accelerated disease progression is observed in the setting of MetS, this is owing to the presence of individual component risk factors rather than to the presence of the syndrome itself.


Journal of the American College of Cardiology | 2010

Clinical Predictors of Plaque Progression Despite Very Low Levels of Low-Density Lipoprotein Cholesterol

Ozgur Bayturan; Samir Kapadia; Stephen J. Nicholls; E. Murat Tuzcu; Mingyuan Shao; Kiyoko Uno; Ajai Shreevatsa; Andrea Lavoie; Kathy Wolski; Paul Schoenhagen; Steven E. Nissen

OBJECTIVES The purpose of this study was to characterize the determinants of plaque progression despite achieving very low levels of low-density lipoprotein cholesterol (LDL-C). BACKGROUND Despite achieving very low levels of LDL-C, many patients continue to demonstrate disease progression and have clinical events. METHODS A total of 3,437 patients with coronary artery disease underwent serial intravascular ultrasound examination in 7 clinical trials. Patients who achieved an on-treatment LDL-C level of <or=70 mg/dl (n = 951) were stratified as progressors (n = 200) and nonprogressors (n = 751) and compared. RESULTS Despite achieving LDL-C <or=70 mg/dl, >20% of patients continued to progress. There were no demographic differences between groups. Progressors demonstrated higher baseline levels of glucose (117.1 +/- 42.5 mg/dl vs. 112.1 +/- 40.0 mg/dl, p = 0.02), triglycerides (157.5 mg/dl vs. 133.0 mg/dl, p = 0.004), and a smaller decrease of apolipoprotein B (-25.1 +/- 3.4 mg/dl vs. -27.4 +/- 3.35 mg/dl, p = 0.01) at follow-up. Multivariable analysis revealed that independently associated risk factors of progression in patients with LDL-C <or=70 mg/dl included baseline percent atheroma volume (p = 0.001), presence of diabetes mellitus (p = 0.02), increase in systolic blood pressure (p = 0.001), less increase in high-density lipoprotein cholesterol (p = 0.01), and a smaller decrease in apolipoprotein B levels (p = 0.001), but not changes in C-reactive protein (p = 0.78) or LDL-C (p = 0.84). CONCLUSIONS Residual risk factors are associated with the likelihood of disease progression in patients who achieve very low LDL-C levels. In addition, the association between apolipoprotein B and atheroma progression highlights the potential importance of LDL particle concentration in patients with optimal LDL-C control. This finding highlights the need for intensive modification of global risk in patients with coronary artery disease.


Journal of the American College of Cardiology | 2011

Lowering the triglyceride/high-density lipoprotein cholesterol ratio is associated with the beneficial impact of pioglitazone on progression of coronary atherosclerosis in diabetic patients: insights from the PERISCOPE (Pioglitazone Effect on Regression of Intravascular Sonographic Coronary Obstruction Prospective Evaluation) study.

Stephen J. Nicholls; E. Murat Tuzcu; Kathy Wolski; Ozgur Bayturan; Andrea Lavoie; Kiyoko Uno; Stuart Kupfer; Alfonso Perez; Richard W. Nesto; Steven E. Nissen

OBJECTIVES The purpose of this study was to determine the factors associated with the favorable effect of pioglitazone on atheroma progression. BACKGROUND Diabetes mellitus is associated with accelerated coronary atheroma progression. Pioglitazone slowed progression compared with glimepiride in this population. METHODS In all, 360 diabetic patients with coronary artery disease were treated with pioglitazone or glimepiride for 18 months in the PERISCOPE (Pioglitazone Effect on Regression of Intravascular Sonographic Coronary Obstruction Prospective Evaluation) study. Coronary atheroma progression was evaluated by serial intravascular ultrasound. The relationship between changes in biochemical parameters, percent atheroma volume, and total atheroma volume was investigated. RESULTS Pioglitazone-treated patients demonstrated greater increases in high-density lipoprotein cholesterol (HDL-C) and reductions in glycated hemoglobin, triglycerides, and C-reactive protein. Significant correlations were observed between changes in percent atheroma volume and triglycerides (r = 0.15, p = 0.04), triglyceride/HDL-C ratio (r = 0.16, p = 0.03), and glycated hemoglobin (r = 0.16, p = 0.03) with pioglitazone, and changes in low-density lipoprotein cholesterol (r = -0.15, p = 0.05), apolipoprotein B (r = -0.16, p = 0.04), and apolipoprotein A-I (r = -0.20, p = 0.01) with glimepiride. Substantial atheroma regression, compared to progression, was associated with greater relative increases in HDL-C (14.2% vs. 7.8%, p = 0.04), relative decreases in triglycerides (-13.3% vs. -1.9%, p = 0.045), triglyceride/HDL-C ratio (-22.5 vs. -9.9%, p = 0.05), and decrease in glycated hemoglobin (-0.6% vs. -0.3%, p = 0.01). Multivariable analysis revealed that pioglitazone-induced effects on triglyceride/HDL-C were associated with changes in percent atheroma volume (p = 0.03) and total atheroma volume (p = 0.02). CONCLUSIONS Favorable effects of pioglitazone on the triglyceride/HDL-C ratio correlated with delayed atheroma progression in diabetic patients. This finding highlights the potential importance of targeting atherogenic dyslipidemia in diabetic patients with coronary artery disease.


American Journal of Cardiology | 2010

Comparison of Rates of Progression of Coronary Atherosclerosis in Patients With Diabetes Mellitus Versus Those With the Metabolic Syndrome

Ozgur Bayturan; E. Murat Tuzcu; Kiyoko Uno; Andrea Lavoie; Tingfei Hu; Ajai Shreevatsa; Kathy Wolski; Paul Schoenhagen; Samir Kapadia; Steven E. Nissen; Stephen J. Nicholls

Diabetes mellitus (DM) and metabolic syndrome (MS) are associated with adverse cardiovascular outcomes. However, the extent and progression of coronary atherosclerosis for these conditions have not been directly compared. Three thousand four hundred fifty-nine patients with coronary artery disease underwent serial evaluation of atheroma burden by intravascular ultrasound. Patients with DM, MS, or neither diagnosis were compared with regard to plaque burden, progression, and arterial remodeling. Among the 3 groups, patients with MS had the largest number of individual cardiovascular risk factors. Patients with DM demonstrated more extensive atherosclerosis burden with a greater percent atheroma volume compared to patients with MS or those with neither diagnosis (40.3 +/- 9.0%, 37.6 +/- 8.9%, and 38.1 +/- 9.1%, p <0.001) and total atheroma volume (198.3 +/- 85.9, 190.7 +/- 85.0, and 186.3 +/- 79.1 mm(3), p = 0.05). MS compared to neither diagnosis was accompanied by expansion of the external elastic membrane (501.3 +/- 174.3 vs 484.4 +/- 160.7 mm(3), p = 0.02), whereas DM was associated with lumen constriction (290.6 +/- 111.7 vs 298.1 +/- 105.5 mm(3), p <0.0001). On serial evaluation, DM, but not MS, was associated with greater progression of percent atheroma volume compared to neither diagnosis (+0.8 +/- 0.3, +0.3 +/- 0.2, and +0.1 +/- 0.2%, p <0.0001) and total atheroma volume (-1.0 +/- 1.8, -3.3 +/- 1.8, and -4.0 +/- 1.8 mm(3), p = 0.001). Meeting criteria for MS was not associated with greater disease progression in patients with DM. In conclusion, despite having fewer individual risk factors, DM is associated with greater plaque progression and more constrictive remodeling than MS. This finding highlights the deleterious effects of DM on the arterial wall independent of its associated metabolic abnormalities.


Sleep and Breathing | 2008

Effect of CPAP therapy on catathrenia and OSA: a case report and review of the literature

Murat Songu; Hikmet Yilmaz; Ali Vefa Yuceturk; Kivanc Gunhan; Aysun Ince; Ozgur Bayturan

IntroductionCatathrenia is a rare, idiopathic, sleep-related respiratory condition characterized by irregular groans, which occur during prolonged expiration in sleep. The origins of catathrenia remain inexplicable, the long-term prognosis unexplained. Moreover, empirical treatment with neither pharmacological nor non-pharmacological approaches was satisfactory.Case reportWe report a case of catathrenia with concurrent obstructive sleep apnea complicated with pulmonary hypertension and reviewed the literature.DiscussionTreatment with nasal continuous positive airway pressure resulted in marked improvement of catathrenia, obstructive sleep apnea, daytime dyspnea, and pulmonary hypertension for our patient. We think that nasal continuous positive airway pressure can be an option for the treatment of this infrequent but sometimes very disturbing sleep disorder.


Heart | 2010

Coronary intravascular ultrasound: a closer view

E. Murat Tuzcu; Ozgur Bayturan; Samir Kapadia

Intravascular ultrasound (IVUS) is an invasive tomographic imaging modality, providing images of coronary arteries and other blood vessels. Over the last 20 years IVUS has evolved into an excellent adjunct to coronary angiography. Although coronary angiography continues to be the standard tool to assess the coronary artery lumen, angiography does not supply direct information about the plaque and vessel wall. IVUS provides complementary diagnostic information about the artery wall which cannot be obtained by angiography alone. IVUS systems contain a special transducer mounted catheter and an electronics console to reconstruct the image. The ultrasound signal is produced in the transducer by passing an electrical current through the piezoelectric (pressure-electric) crystalline material (usually ceramic) that expands and contracts when electrically excited. After reflection from tissue, part of the ultrasound energy returns to the transducer and is converted into the image. High ultrasound frequencies (20–40 MHz) are employed resulting in an axial resolution in the range of 80–150 μm and lateral resolution of 200–250 μm.1 ### Catheter technology Currently available monorail rapid exchange intracoronary ultrasound catheters have an outer diameter of between 2.6–3.5 French (0.87–1.17 mm diameter) which can be advanced through a 6 French guide catheter. Two transducer designs are commonly used: the mechanically rotating transducer and the electronically switched phased array system. Mechanical systems consist of a drive cable to rotate a single transducer at the catheter tip at 1800 rpm (30 revolutions per second), sweeping an ultrasound beam perpendicular to the catheter. At approximately 1° increments, the transducer sends and receives ultrasound signals. In mechanical catheter systems, the imaging transducer is inside a protective sheath, through which the imaging catheter is advanced and pulled back. Electronic systems , also referred to as the solid state IVUS system, have multiple transducer elements (up to 64) arranged in an annular array rather than a single rotating transducer. The transducers …


European Journal of Preventive Cardiology | 2017

Atrial fibrillation, progression of coronary atherosclerosis and myocardial infarction:

Ozgur Bayturan; Rishi Puri; E. Murat Tuzcu; Mingyuan Shao; Kathy Wolski; Paul Schoenhagen; Samir Kapadia; Steven E. Nissen; Prashanthan Sanders; Stephen J. Nicholls

Background Despite atrial fibrillation representing an established risk factor for stroke, the association between atrial fibrillation and both progression of coronary atherosclerosis and major adverse cardiovascular events is not well characterized. We assessed the serial measures of coronary atheroma burden and cardiovascular outcomes in patients with and without atrial fibrillation. Methods Data were analyzed from nine clinical trials involving 4966 patients with coronary artery disease undergoing serial intravascular ultrasonography at 18–24 month intervals to assess changes in percent atheroma volume (PAV). Using a propensity weighted analysis, and following adjustment for baseline variables, patients with (n = 190) or without (n = 4776) atrial fibrillation were compared with regard to coronary plaque volume and major adverse cardiovascular events (death, myocardial infarction, and stroke). Results Atrial fibrillation patients demonstrated lower baseline PAV (36.0 ± 8.9 vs. 38.1 ± 8.9%, p = 0.002) and less PAV progression (–0.07 ± 0.34 vs. + 0.23 ± 0.34%, p = 0.001) compared with the non-atrial fibrillation group. Multivariable analysis revealed atrial fibrillation to independently predict both myocardial infarction [HR, 2.41 (1.74,3.35), p<0.001] 2.41 (1.74, 3.35), p < 0.00) and major adverse cardiovascular events [HR, 2.2, (1.66, 2.92), p<0.001] 2.20 (1.66, 2.92), p < 0.001]. Kaplan–Meier analysis showed that atrial fibrillation compared with non-atrial fibrillation patients had a significantly higher two-year cumulative incidence of overall major adverse cardiovascular events (4.4 vs. 2.0%, log-rank p = 0.02) and myocardial infarction (3.3 vs. 1.5%, log-rank p = 0.05). Conclusions The presence of atrial fibrillation independently associates with a heightened risk of myocardial infarction despite a lower baseline burden and progression rate of coronary atheroma. Further studies are necessary to define the pathogenesis of myocardial infarction in the setting of atrial fibrillation.


American Journal of Cardiology | 2010

Plaque Progression in Coronary Arteries With Minimal Luminal Obstruction in Intravascular Ultrasound Atherosclerosis Trials

Andrea Lavoie; Ozgur Bayturan; Kiyoko Uno; Amy Hsu; Kathy Wolski; Paul Schoenhagen; Samir Kapadia; E. Murat Tuzcu; Steven E. Nissen; Stephen J. Nicholls

The relation among the burden of disease, progression of atherosclerosis, and remodeling in angiographically minimally diseased coronary arteries has not been defined. The present analysis included 1,906 patients who participated in 5 prospective clinical trials examining atheroma progression using intravascular ultrasonography. For the present analysis, the patients were stratified according to baseline quantitative coronary angiographic stenosis: <20%, 20% to 35%, and >35%. Patients with a lesser degree of luminal stenosis had less atherosclerosis. However, in the arteries with minimal angiographic stenosis, a large percentage of images contained atheroma, demonstrating the diffuse nature of coronary atherosclerosis. All 3 groups showed evidence of disease progression. The serial changes in vessel dimensions revealed that both the external elastic membrane and lumen volumes decreased in all 3 subgroups, in keeping with vessel and luminal constriction. In conclusion, these findings have demonstrated that patients with at least one luminal stenosis have diffuse atherosclerosis that progressed during 18 to 24 months, making them a target for therapeutic intervention. These minimally diseased arteries demonstrated evidence of vessel and luminal constriction, regardless of the angiographic appearance.


Journal of Cardiothoracic Surgery | 2014

Evaluation of the prevalence of coronary artery disease in patients with valvular heart disease

Zeynep Yapan Emren; Sadık Volkan Emren; Barış Kılıçaslan; Hatice Solmaz; İbrahim Susam; Ahmet Sayın; Burçin Abud; Mehmet Aydin; Ozgur Bayturan

ObjectivesThe aim of the present study was to retrospectively evaluate the prevalence of concurrent coronary artery disease in patients who underwent surgery due to severe valvular heart disease. The study also investigated the association of coronary artery disease with the type of valvular heart disease.Materials and methodsA total of 241 patients (123 females [51%]), who had underwent single valvular heart surgery, were included in the study. The patients who underwent valve replacement surgery were divided into four groups: patients with severe mitral stenosis (MS), patients with severe mitral regurgitation (MR), patients with severe aortic regurgitation (AR), and patients with severe aortic stenosis (AS). Age, DM, HT, history of smoking, and LDL values were recorded as the risk factors for CAD.ResultsCoronary artery disease was detected in 26.4% of patients with mitral stenosis and 57.7% of patients with aortic stenosis. Of the patients with mitral insufficiency, 41.9% had CAD, and 44.4% of the patients with aortic insufficiency had CAD.ConclusionThe comparison of MS and AS groups revealed significantly higher prevalence of CAD in the AS group. There was no statistically significant difference between the MR and AR groups in terms of the prevalence of CAD. The comparison of MS and MR groups revealed significantly higher prevalence of CAD in the MR group. Furthermore, the comparison of these groups in terms of the extensiveness of the coronary artery disease revealed significantly higher Gensini score in the MR group.

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Ozan Utuk

Celal Bayar University

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