Sinan Altan Kocaman

Prognostic Value of Fractional Flow Reserve: Linking Physiologic Severity to Clinical Outcomes

BACKGROUND Fractional flow reserve (FFR) has become an established tool for guiding treatment, but its graded relationship to clinical outcomes as modulated by medical therapy versus revascularization remains unclear. OBJECTIVES The study hypothesized that FFR displays a continuous relationship between its numeric value and prognosis, such that lower FFR values confer a higher risk and therefore receive larger absolute benefits from revascularization. METHODS Meta-analysis of study- and patient-level data investigated prognosis after FFR measurement. An interaction term between FFR and revascularization status allowed for an outcomes-based threshold. RESULTS A total of 9,173 (study-level) and 6,961 (patient-level) lesions were included with a median follow-up of 16 and 14 months, respectively. Clinical events increased as FFR decreased, and revascularization showed larger net benefit for lower baseline FFR values. Outcomes-derived FFR thresholds generally occurred around the range 0.75 to 0.80, although limited due to confounding by indication. FFR measured immediately after stenting also showed an inverse relationship with prognosis (hazard ratio: 0.86, 95% confidence interval: 0.80 to 0.93; p < 0.001). An FFR-assisted strategy led to revascularization roughly half as often as an anatomy-based strategy, but with 20% fewer adverse events and 10% better angina relief. CONCLUSIONS FFR demonstrates a continuous and independent relationship with subsequent outcomes, modulated by medical therapy versus revascularization. Lesions with lower FFR values receive larger absolute benefits from revascularization. Measurement of FFR immediately after stenting also shows an inverse gradient of risk, likely from residual diffuse disease. An FFR-guided revascularization strategy significantly reduces events and increases freedom from angina with fewer procedures than an anatomy-based strategy.

Plasma neutrophil gelatinase-associated lipocalin levels in acute myocardial infarction and stable coronary artery disease

IntroductionInflammation and polymorphonuclear neutrophils are shown to be important in the pathogenesis of acute myocardial infarction (AMI). Neutrophil gelatinase-associated lipocalin (NGAL) is secreted from neutrophils and may increase the proteolytic activity within the atherosclerotic plaque. We aimed to investigate whether the plasma levels of NGAL are higher in patients with AMI compared with stable coronary artery disease (CAD). MethodsThe study population consisted of 128 eligible patients who underwent coronary angiography with the clinical diagnosis of CAD. Of the 128 patients included in the study, the diagnosis was ST-segment elevation myocardial infarction (STEMI) in 53 patients, non-ST-elevation myocardial infarction (NSTEMI) in 38 patients and stable CAD in 37 patients. Plasma level of NGAL was measured in all patients with an enzyme-linked immunosorbent assay method. We compared the plasma NGAL levels among the groups. ResultsWe found higher plasma NGAL levels in patients with AMI compared with the patients with stable CAD (146±23 vs. 101±53 ng/ml, P<0.001). The plasma NGAL levels between the subgroups of AMI were similar (145±23.9 vs. 145±23.4 ng/ml, P=not significant). In multivariate analysis, the independent factors related to AMI were current smoking (P=0.024), extent and severity of coronary atherosclerosis (P=0.030), and NGAL levels. The plasma NGAL level was independently related to the existence of AMI (odds ratio: 1.045, 95% confidence interval: 1.019–1.072, P=0.001). In patients with plasma NGAL level above 127 ng/ml, we observed a 12 times higher incidence of AMI (odds ratio: 12.2, 95% confidence interval: 2.3–64, P=0.003). ConclusionThe plasma level of NGAL is higher in patients with AMI compared with the patients with stable CAD. This finding may suggest an active pathophysiological role for NGAL in development of acute coronary events.

Independent relationship of serum uric acid levels with leukocytes and coronary atherosclerotic burden.

BACKGROUND AND AIM Epidemiological studies have shown that increased serum uric acid (SUA) level is associated with coronary artery disease (CAD). Leukocytes have been shown to play an important role in the atherosclerotic process. The aim of the study was to investigate whether there is any relationship among SUA, leukocyte counts and coronary atherosclerotic burden in patients who are suspected of having CAD. METHOD AND RESULTS We enrolled 690 eligible patients who had undergone coronary angiography between October 2005 and June 2006 in a consecutive manner. The relationship of SUA with total and differential leukocyte counts and CAD was investigated. Serum uric acid levels (5.57+/-1.64 vs 4.63+/-1.27 mg/dl, p<0.001) and leukocytes were higher in patients with CAD than those with normal coronary arteries (NCA). When we divided the patients into four groups according to the quartiles of SUA, we found that the monocyte count was prominently related with SUA (478+/-165, 553+/-177, 565+/-199 and 607+/-229 mm(-)(3), Q1-Q4, p<0.001). In multivariate analysis, SUA was an independent predictor of CAD (OR, 1.270; 95% CI, 1.087-1.484, p=0.003). When we performed multiple linear regression analyses to determine the independent predictors of inflammatory cells in blood, we found a strong, positive and independent relationship between SUA with neutrophils (beta+/-SE: 206+/-60, p=0.001) and monocytes (beta+/-SE: 35+/-7, p<0.001). CONCLUSION Our study results demonstrated that neutrophils and monocytes which play an important role in inflammation and atherosclerosis were independently related with SUA. This finding suggests an important epidemiologic relation and may provide a possible causative mechanism of SUA in atherosclerotic process.

Increased pulse wave velocity in patients with panic disorder: Independent vascular influence of panic disorder on arterial stiffness

OBJECTIVE Acute and chronic mental stress and many psychiatric disorders have been accepted as a cause of cardiovascular disease. Panic disorder, a subtype of anxiety disorder, has been associated with increased risk of fatal myocardial infarction and sudden cardiac death in epidemiological studies. Carotid-femoral pulse wave velocity (CF-PWV) is currently the gold standard measurement of arterial stiffness. CF-PWV is a well-recognized predictor of an adverse cardiovascular outcome with higher predictive value than classical cardiovascular risk factors. The aim of our study is to measure PWV as the surrogate of arterial stiffness and vascular involvement in patients with panic disorder. METHODS Forty-two patients with PD, and 30 control participants were included in the study. Patients with hypertension, diabetes mellitus, or the history of any cardiovascular disease were excluded from study. RESULTS Baseline characteristics were not significantly different between the two groups, except carotid-femoral pulse wave velocity (PD vs. control; 7.51±2.02 vs. 6.24±1.09 m/s, p=0.001), heart rate, and smoking status. Additionally, CF-PWV positively correlated with age (r=0.250, p=0.034), heart rate (r=0.284, p=0.017), systolic and diastolic blood pressure (r=0.393, p=0.001 and r=0.286, p=0.015, respectively) significantly. However, only the presence of panic disorder was independently related to PWV (βeta: 0.317, p=0.011) in the multivariate analysis including age, heart rate, smoking status and blood pressure measurements. CONCLUSION Increased pulse wave velocity in patients with panic disorder may justify the associated risk as documented in previous studies, and may be useful in identifying the patients with higher risk of future cardiovascular complications.

Effect of transradial coronary angiography procedure on vascular diameter and vasodilator functions in the access site.

The present study aimed to investigate the long-term effects of transradial procedures on the radial artery diameter and vasodilator properties. The study included a total of 35 patients (28 males and 7 females) who underwent left transradial coronary angiography with an appropriate indication. The radial artery diameters were measured before and after flow-mediated vasodilation (FMD) and nitrate-mediated vasodilation (NMD). The nonintervened right radial artery served as the control. A marked narrowing in the diameter of the intervened radial artery and impaired FMD response indicating endothelial dysfunction were observed at a mean of 9 months after transradial intervention. Structural and functional changes should be taken into consideration if previously intervened radial artery would be used for interventions, such as arterial bypass graft or dialysis fistula.

The independent relationship of epicardial adipose tissue with carotid intima-media thickness and endothelial functions: the association of pulse wave velocity with the active facilitated arterial conduction concept.

BackgroundHypertension, identifiable by elevated blood pressure (BP), is a heterogeneous multifactorial disorder. Epicardial adipose tissue (EAT), a special fat depot that is related to visceral fat rather than total adiposity, shares the same microcirculation with myocardial tissue and coronary vessels. Recent studies have identified EAT as an active organ, which secretes several mediators, called adipokines, affecting the vascular system. The aim of this study was to evaluate the potential association between EAT and BP, endothelial function, carotid intima-media thickness (CIMT), and pulse wave velocity (PWV) independent of conventional and novel metabolic risk factors in patients with previously untreated hypertension. Patients and methodsOur study, which has a cross-sectional design, included 107 consecutive untreated hypertensive patients. Vascular status and functions were evaluated using CIMT, PWV, and flow-mediated dilation (FMD) of the brachial artery. The values of BP were obtained both by the traditional auscultatory method using a sphygmomanometer in an office and by ambulatory BP measurement. ResultsWhen we stratified the patients into three groups according to increased EAT values, CIMT (P<0.001), presence of carotid plaque (P=0.026), and BP values (P=0.001) were increased in the higher tertile compared with the lower tertile. FMD of the brachial artery decreased significantly with increasing EAT thickness (P<0.001). There was a significant, strong, and negative association between CIMT and FMD (r=−0.604, P<0.001). CIMT correlated positively to age (r=0.404, P<0.001), EAT (r=0.517, P<0.001), office systolic BP (r=0.241, P=0.016), ambulatory systolic BP (r=0.419, P<0.001), and diastolic BP (r=0.360, P=0.002). FMD correlated negatively to age (r=−0.390, P<0.001), EAT (r=−0.495, P<0.001), ambulatory systolic (r=−0.338, P=0.006), and diastolic BP (r=−0.281, P=0.024). Multivariate linear regression analyses, carried out to identify predictors of CIMT and FMD, showed only age, EAT, and mean ambulatory BP as independent predictors of both CIMT and FMD. ConclusionOur study showed that EAT is an independent factor of adverse changes in CIMT, FMD, and PWV. Future studies, investigating the vascular influence of EAT at the molecular level, may provide therapeutic options to prevent its adverse vascular interactions.

Non-dipping pattern in untreated hypertensive patients is related to increased pulse wave velocity independent of raised nocturnal blood pressure

Abstract Background. Non-dipper pattern, characterized by diminished nocturnal decline in blood pressure (BP), is associated with an increase in cardiovascular events. Carotid–femoral pulse wave velocity (CF-PWV) has been accepted as the gold standard measurement of arterial stiffness. CF-PWV is a well-recognized predictor of an adverse cardiovascular outcome with higher predictive value than classical cardiovascular risk factors. In this study, we investigated the association between PWV as the surrogate of arterial stiffness and non-dipper pattern in untreated hypertensive patients. Methods. The present study was cross-sectional and observational. Hypertensive patients were diagnosed according to ambulatory BP measurements (mean BP

The importance of fragmented QRS complexes in prediction of myocardial infarction and reperfusion parameters in patients undergoing primary percutaneous coronary intervention.

130/80 mmHg). Eighty-four hypertensive patients, consulted for initial evaluation of hypertension, were enrolled. CF-PWV as the indicator of arterial stiffness was measured by a validated tonometry system (SphygmoCor). Patients with the history of any cardiovascular disease were excluded from the study. Results. Fifty-six patients had non-dipper pattern and 28 patients had dipper pattern in the study. Baseline characteristics were not significantly different between the two groups, except the CF-PWV (non-dipper vs dipper; 8.91 ± 2.53 vs 7.66 ± 1.08 m/s, p = 0.002), female gender (55% vs 32%, p = 0.045) and nocturnal BP measurements (for mean BP; 106 ± 11 vs 92 ± 8 mmHg, p < 0.001). Multiple logistic regression analysis including age, gender, BP and PWV measurements, revealed female gender (odds ratio, OR = 5.112, 95% confidence interval, CI 1.282–20.4, p = 0.021), nocturnal mean BP (OR = 1.243, 95% CI 1.107–1.396, p < 0.001) and CF-PWV (OR = 1.992, 95% CI 1.240–3.198, p = 0.004) as the independent predictors of non-dipper hypertensive pattern. Conclusion. Our results suggest that diminished nocturnal decline in BP is independently associated with PWV and nocturnal BP rather than daytime BP. Non-dipper pattern, mainly related to increased PWV and impaired modulation of vascular smooth muscle tone during the night, may justify an increased cardiovascular risk in these patients.

Relationship between total and differential leukocyte counts and isolated coronary artery ectasia.

OBJECTIVES The QRS complex fragmentations (fQRS) frequently seen on admission electrocardiograms (ECGs) with narrow or wide QRS complex are associated with increased morbidity and mortality. The causative relationship between fQRS and cardiac fibrosis is known, but the relation of fragmented QRS before and after primary percutaneous coronary intervention (p-PCI) with myocardial infarction and reperfusion parameters has not been studied until now. STUDY DESIGN The study included 184 consecutive patients with ST elevation myocardial infarction (STEMI) who underwent p-PCI. Presence or absence of fQRS on pre- and post-PCI ECGs and its change following PCI were investigated. In addition, independent predictors of fQRS were also investigated. Patients with significant organic valve disease and patients having any QRS morphology with QRS duration ?120 ms as well as patients with permanent pacemakers were excluded from the study. RESULTS Patients with fQRS on admission ECG had higher leukocyte counts (p=0.001), higher CK-MB (p=0.001) and troponin levels (p=0.005), increased pain to balloon time (p=0.004), higher Killip score (p<0.001), prolonged QRS time (p<0.001), higher Gensini score (p<0.001) and more frequent Q waves on ECG (p<0.001) in comparison to patients with non-fragmented QRS. In addition, these patients usually had an infarction of anterior territory related to a lesion in proximal LAD and wider jeopardized myocardium (p<0.001). fQRS was significantly related to infarction and myocardial reperfusion parameters before and after p-PCI. In the setting of STEMI, absence of fQRS on admission ECG predicted increased ST resolution, higher reduction in QRS duration, and better myocardial reperfusion. CONCLUSION FQRS may be useful in identifying patients at higher cardiac risk with larger areas of ischemic jeopardized or necrotic myocardium.

The reliability of fractional flow reserve measurement in patients with diabetes mellitus.

BackgroundCoronary artery ectasia (CAE) is a clinical entity characterized by localized or diffuse dilatation of more than or equal to 1.5 times that of the normal adjacent segments of vessels. Although the etiopathogenesis is not clearly understood, some studies have shown that CAE may be a form of atherosclerosis and has more potent inflammatory properties. Leukocytes have a crucial role in the development of inflammatory processes. We aimed to investigate a possible relationship between leukocytes and the coronary ectatic process without coronary artery disease (CAD) and to compare it with the inflammatory atherosclerotic process related to leukocytes. Methods and resultsThe study population consisted of 371 patients. We divided the patients into three groups: 42 patients with isolated CAE as group I, 279 patients with CAD as group II, and 50 control participants with normal coronary arteries (NCA) as group III. The counts of total leukocytes (7348±1898, 7569±1619, and 6770±1748 cells/mm3, P=0.002), neutrophils (4260±2169, 4529±1380, and 4040±1649 cells/mm3, P=0.037) and monocytes (630±216, 583±198, and 480±140 cells/mm3, P<0.001) were significantly different among the CAE, CAD, and NCA groups, respectively. The CAE group also had significantly higher leukocyte and subtype counts than the nonobstructive CAD subgroup and NCA group. ConclusionThis study demonstrates that total and differential leukocyte counts, which play an important role in inflammation, are increased in patients with isolated CAE. In conclusion, this studys findings show that leukocytes may play an important role in the development of CAE independently of the atherosclerotic process.