Peripheral Artery Disease Diagnosed by Pulse Palpation as a Predictor of Coronary Artery Disease in Patients with Chronic Kidney Disease.

There is a need of simple, inexpensive, and reliable noninvasive testing to predict coronary artery disease (CAD) in patients with chronic kidney disease (CKD), where the prevalence of cardiovascular (CV) events and death is elevated. We analyzed the association between peripheral artery disease (PAD) and CAD in 201 patients with stage 5 CKD on dialysis using a prospective observational cohort. Diagnosis of PAD by both palpation and USD were significantly correlated. In patients with PAD diagnosed by palpation, CAD was observed in 80%, while in those diagnosed by USD, CAD was present in 79.1%. The absence of a pulse by palpation predicted CAD with a sensitivity of 55% and a specificity of 76%; USD showed a sensitivity of 62% and specificity of 60% to predict CAD. The risk of combined serious CV events and death was significantly higher in subjects with PAD diagnosed by palpation, but not by USD. PAD assessed by palpation also correlated with the occurrence of multivessel CAD and with the probability of coronary intervention. Both methods are moderately useful for predicting CAD, but PAD diagnosis by palpation was a better predictor of combined CV events and death and was also associated with CAD severity and likelihood of intervention.

Interdialytic Blood Pressure and Risk of Cardiovascular Events and Death in Hemodialysis Patients.

INTRODUCTION: Normal (120-140 mm Hg) systolic peridialysis blood pressure (BP) is associated with higher mortality in hemodialysis (HD) patients. AIM: We explored the relationship between hypertension and BP on outcomes using data collected at the interdialytic period. METHODS: This was a single-center observational cohort study with 2672 HD patients. BP was determined at inception, in mid-week, between 2 consecutive dialysis sessions. Hypertension was defined as systolic BP ≥ 140 mm Hg and/or diastolic BP ≥ 90 mm Hg. Endpoints were major CV events and all-cause mortality. RESULTS: During a median follow-up of 31 months, 761 patients (28%) experienced CV events and 1181 (44%) died. Hypertensive patients had lower survival free of CV than normotensive patients (P = 0.031). No difference occurred in the incidence of death between groups. Compared with the reference category of SBP ≥ 171 mmHg, the incidence of cardiovascular events was reduced in patients with SBP 101-110 (HR 0.647, 95% CI 0.455 to 0.920), 111-120 (HR 0.663, 95%CI 0.492 to 0.894), 121-130 (HR 0.747, 95%CI 0.569 to 0.981), and 131-140 (HR 0.757, 95%CI 0.596 to 0.962). On multivariate analysis, systolic and diastolic BP were not independent predictors of CV events or death. Normal interdialytic BP was not associated with mortality or CV events, and hypertension predicted an increased probability of CV complications. CONCLUSIONS: Interdialytic BP may be preferred to guide treatment decisions, and HD patients should be treated according to guidelines for the general population until specific BP targets for this population are identified.

Evolving Management Paradigm for Stable Ischemic Heart Disease Patients: JACC Review Topic of the Week.

Management of stable coronary artery disease (CAD) has been based on the assumption that flow-limiting atherosclerotic obstructions are the proximate cause of angina and myocardial ischemia in most patients and represent an important target for revascularization. However, the role of revascularization in reducing long-term cardiac events in these patients has been limited mainly to those with left main disease, 3-vessel disease with diabetes, or decreased ejection fraction. Mounting evidence indicates that nonepicardial coronary causes of angina and ischemia, including coronary microvascular dysfunction, vasospastic disorders, and derangements of myocardial metabolism, are more prevalent than flow-limiting stenoses, raising concerns that many important causes other than epicardial CAD are neither considered nor probed diagnostically. There is a need for a more inclusive management paradigm that uncouples the singular association between epicardial CAD and revascularization and better aligns diagnostic approaches that tailor treatment to the underlying mechanisms and precipitants of angina and ischemia in contemporary clinical practice.

Unraveling the interplay between dipeptidyl peptidase 4 and the renin-angiotensin system in heart failure.

AIMS: Emerging evidence suggests the existence of a crosstalk between dipeptidyl peptidase 4 (DPP4) and the renin-angiotensin system (RAS). Therefore, combined inhibition of DPP4 and RAS may produce similar pharmacological effects rather than being additive. This study tested the hypothesis that combining an inhibitor of DPP4 with an angiotensin II (Ang II) receptor blocker does not provide additional cardioprotection compared to monotherapy in heart failure (HF) rats. MAIN METHODS: Male Wistar rats were subjected to left ventricle (LV) radiofrequency ablation or sham operation. Six weeks after surgery, radiofrequency-ablated rats who developed HF were assigned into four groups and received vehicle (water), vildagliptin, valsartan, or both drugs, for four weeks by oral gavage. KEY FINDINGS: Vildagliptin and valsartan in monotherapy reduced LV hypertrophy, alleviated cardiac interstitial fibrosis, and improved systolic and diastolic function in HF rats, with no additional effect of combination treatment. HF rats displayed higher cardiac and serum DPP4 activity and abundance than sham. Surprisingly, not only vildagliptin but also valsartan in monotherapy downregulated the catalytic function and expression levels of systemic and cardiac DPP4. Moreover, vildagliptin and valsartan alone or in combination comparably upregulate the components of the cardiac ACE2/Ang-(1-7)/MasR while downregulating the ACE/Ang II/AT1R axis. SIGNIFICANCE: Vildagliptin or valsartan alone is as effective as combined to treat cardiac dysfunction and remodeling in experimental HF. DPP4 inhibition downregulates classic RAS components, and pharmacological RAS blockade downregulates DPP4 in the heart and serum of HF rats. This interplay between DPP4 and RAS may affect HF progression and pharmacotherapy.

Invasive coronary artery disease assessment and myocardial infarction in patients on renal replacement therapy.

BACKGROUND: The incidence of myocardial infarction (MI) is elevated in patients receiving renal replacement therapy (RRT). We hypothesized that an invasive strategy of assessment of coronary artery disease (CAD) will identify patients more prone to developing MI. METHODS: This was a single-center observational cohort study that included 1678 patients receiving RRT (hemodialysis and renal transplantation) assessed for CAD prospectively and analyzed retrospectively. Endpoints were the incidence of MI and death. RESULTS: The median follow-up was 43 months, and 180 patients experienced an MI with a mortality rate of 74%. Multivariate analysis showed that diabetes (HR 1.633; 95% CI 1.165-2.289), prior MI (HR 1.724; 95% CI 1.153-2.579), and CAD (HR 2.073; 95% CI 1.400-3.071) were predictors of MI. Altered myocardial scan did not correlate with MI. At the discretion of the attending physicians, 20/180 patients (11%) underwent coronary intervention that was associated with a higher cumulative survival (Log-rank 0.007). CONCLUSION: Patients with CAD suffered an MI more frequently, independently of symptoms and risk factors for MI, including noninvasive testing. Because of the elevated rate of the lethality of MI, invasive coronary studies may be indicated in select patients on RRT. Once an MI occurs, our data suggest that an invasive therapeutic approach is warranted.

Diastolic and systolic left ventricular dysfunction and mortality in chronic kidney disease patients on haemodialysis.

AIMS: Left ventricular diastolic dysfunction (LVDD) and LV systolic dysfunction (LVSD) are prevalent in CKD, but their prognostic relevance is debatable. We intent to verify whether LVDD and LVSD are independently predictive of all-cause mortality and if they have comparable or different effects on outcomes. METHODS: A retrospective analysis was conducted of the echocardiographic data of 1285 haemodialysis patients followed up until death or transplantation. LVDD was classified into 4 grades of severity. Endpoint was all-cause mortality. RESULTS: During a follow-up of 30 months, 419/1285 (33%) patients died, 224 (53%) due to CV events. LVDD occurred in 75% of patients, grade 1 DD was the prevalent diastolic abnormality, and pseudonormal pattern was the predominant form of moderate-severe DD. Moderate-severe LVDD (HR 1.379, CI% 1.074-1.770) and LVSD (HR 1.814, CI% 1.265-2.576) independently predicted death; a graded, progressive association was found between LVDD categories and the risk of death; and the impact of isolated severe-moderate LVDD on the risk of death was comparable to that exercised by isolated compromised LV systolic function. CONCLUSION: Moderate-severe LVDD and LVSD were independently associated with a higher probability of death and had a similar impact on survival. A progressive association was observed between LVDD grades and mortality.

The Role of Ivabradine in Managing Symptomatic Patients with Chronic Coronary Syndromes: A Clinically Oriented Approach.

Angina is a significant contributor to disability and impairment in quality of life in patients with chronic coronary syndromes (CCS). An elevated heart rate (HR) may trigger myocardial ischemia by increasing oxygen consumption and decreasing the diastolic time, compromising the coronary flow. HR-lowering strategies offer symptom control and prevent cardiovascular events in subgroups of patients with CCS. However, the best therapeutic approach to achieve the desired HR in patients with CCS can be challenging based on efficacy and tolerability. Guidelines usually propose ß-blockers and/or non-dihydropyridine calcium channel blockers (CCB) for angina patients with elevated HR. Nonetheless, there is no clear evidence of greater antianginal efficacy of this strategy versus an alternative HR-lowering agent. Ivabradine reduces the HR by blocking the If current in the sinoatrial node without affecting myocardial contractility or vascular tone. The magnitude of the HR reduction by ivabradine is proportional to the initial HR, which decreases the risk of significant bradycardia. Ivabradine increases the diastolic time and the coronary flow reserve to a greater extent than ß-blockers and favors collateralization, improving the regional blood flow. We present two clinical cases of patients with symptomatic CCS in whom HR control with ivabradine was fundamental for symptom control and improvement in left ventricular (LV) function. An earlier combination of ivabradine plus ß-blockers would have provided more rapid symptom control and improved LV function in the first case. In the second case, the primary mechanism responsible for angina was most likely a coronary vasomotor abnormality, in which the use of ß-blockers aggravated the discomfort. The combination of a dihydropyridine CCB plus ivabradine was highly influential in symptom control. Due to its effects beyond HR reduction and good tolerability, ivabradine should be considered an essential ally in managing patients with angina and high HR with or without LV dysfunction.

Diabetes, Cardiovascular Disease, and Cardiovascular Risk in Patients with Chronic Kidney Disease.

INTRODUCTION: It is unclear whether the increased risk associated with diabetes in patients on dialysis is due to diabetes or a consequence of associated cardiovascular disease (CVD). AIM: The purpose of this work was to answer the question: do diabetes and CVD have a similar impact on the incidence of cardiovascular events in patients undergoing maintenance hemodialysis? METHODS: A prespecified protocol was used to prospectively evaluate and follow up 310 diabetic patients on hemodialysis without clinical evidence of CVD and 395 nondiabetic patients with CVD. Endpoint was the incidence of composite CV events and coronary events. RESULTS: The incidence of composite CV events (log-rank = 0.540) and coronary events (log-rank = 0.400) did not differ between groups. Because of the potential influence of occult CVD in patients with diabetes, we repeated the analysis excluding subjects with altered ejection fraction, a myocardial perfusion scan defect, and coronary artery disease in the group of patients with diabetes. Again we found no difference between groups (log-rank = 0.657). CONCLUSION: In patients on hemodialysis, diabetes and CVD carry similar risks for CV events. These results are congruent with the diabetes mellitus-CVD equivalence risk concept reported in the general population.

Early cardiovascular events and cardiovascular death after renal transplantation: role of pretransplant risk factors.

BACKGROUND: The purpose of this study was to verify the risk factors present in patients on the kidney transplant waiting list that may interfere with the incidence of cardiovascular (CV) events and death during the first 12 months after transplantation. METHODS: Based on the data collected prospectively during pretransplant workups, a retrospective study was conducted including 665 patients followed up until death or completing 12 months posttransplantation. Endpoints were the composite incidence of CV events and death. RESULTS: The prevalence of diabetes, LV hypertrophy, and CV disease at baseline was high; 14% of patients had angina, 26% an abnormal myocardial scan, and 47% coronary artery disease. CV events occurred in 53 patients (8.4%) and in 29 (55%) caused death. The independent predictors of events were age ≥ 50 years (HR 2.292; CI% 1.093-4.806), angina (HR 1.969; CI% 1.039-3.732), and altered myocardial scan (HR 1.905, CI% 1.059-3.428). Altered myocardial scan (HR 2.822, 95% CI 1.095-6.660) was also one of the independent predictor of CV death. CONCLUSION: The incidence of CV events and death were predicted by variables associated with myocardial ischemia, a potentially modifiable risk factor. Patients with pretransplantation myocardial ischemia should be considered at a higher risk of developing early CV complications and managed accordingly before, during, and after kidney transplantation.

The Role of the Heart Team in Patients with Diffuse Coronary Artery Disease Undergoing Coronary Artery Bypass Grafting.

BACKGROUND: In patients eligible for coronary artery bypass grafting, no data assess the importance of the Heart Team in programming the best surgical strategy for patients with diffuse coronary artery disease (CAD). This study aims to determine the contribution of the Heart Team in predicting the feasibility of coronary artery bypass graft and angiographic surgical success in these patients based on visual angiographic analysis. METHODS: Patients with diffuse and severe CAD undergoing incomplete coronary artery bypass graft surgery were prospectively included. One-year postoperative coronary angiograms were obtained to evaluate graft occlusion. Two clinical cardiologists, two cardiovascular surgeons, and one interventional cardiologist retrospectively analyzed preoperative angiograms. A subjective scale was applied at a single moment to quantify the chance of successful coronary artery bypass grafting for each coronary territory with anatomical indication for revascularization. Based on individual scores, the Heart Team's and the specialists' scores were calculated and compared. RESULTS: The examiners evaluated 154 coronary territories, of which 85 (55.2%) were protected. The Heart Team's accuracy for predicting the angiographic success of the surgery was 74.9%, almost equal to that of the surgeons alone (73.2%). Only the interventional cardiologist predicted left anterior descending territory grafting success. The Heart Team had good specificity and reasonable sensitivity, and the surgeons had high sensitivity and low specificity in predicting angiographic success. CONCLUSION: The multispecialty Heart Team achieved good accuracy in predicting the angiographic coronary artery bypass graft success in patients with diffuse CAD, with a high specificity and reasonable sensitivity.

Postprandial increase in glucagon-like peptide-1 is blunted in severe heart failure.

The relationship between disturbances in glucose homeostasis and heart failure (HF) progression is bidirectional. However, the mechanisms by which HF intrinsically impairs glucose homeostasis remain unknown. The present study tested the hypothesis that the bioavailability of intact glucagon-like peptide-1 (GLP-1) is affected in HF, possibly contributing to disturbed glucose homeostasis. Serum concentrations of total and intact GLP-1 and insulin were measured after an overnight fast and 15 min after the ingestion of a mixed breakfast meal in 49 non-diabetic patients with severe HF and 40 healthy control subjects. Similarly, fasting and postprandial serum concentrations of these hormones were determined in sham-operated rats, and rats with HF treated with an inhibitor of the GLP-1-degrading enzyme dipeptidyl peptidase-4 (DPP4), vildagliptin, or vehicle for 4 weeks. We found that HF patients displayed a much lower increase in postprandial intact and total GLP-1 levels than controls. The increase in postprandial intact GLP-1 in HF patients correlated negatively with serum brain natriuretic peptide levels and DPP4 activity and positively with the glomerular filtration rate. Likewise, the postprandial increases in both intact and total GLP-1 were blunted in HF rats and were restored by DPP4 inhibition. Additionally, vehicle-treated HF rats displayed glucose intolerance and hyperinsulinemia, whereas normal glucose homeostasis was observed in vildagliptin-treated HF rats. We conclude that the postprandial increase in GLP-1 is blunted in non-diabetic HF. Impaired GLP-1 bioavailability after meal intake correlates with poor prognostic factors and may contribute to the establishment of a vicious cycle between glucose disturbance and HF development and progression.

Cardiovascular risk reduction with periodontal treatment in patients on the waiting list for renal transplantation.

BACKGROUND: Cardiovascular mortality is increased in chronic kidney disease, a condition with a high prevalence of periodontal disease. Whether periodontitis treatment improves prognosis is unknown. METHODS: The effect of periodontal treatment on the incidence of cardiovascular events and death in 206 waitlist hemodialysis subjects was compared with that in 203 historical controls who did not undergo treatment. Patients were followed up for 24 months or until death or transplantation. RESULTS: The prevalence of moderate/severe periodontitis was 74%. Coronary artery disease correlated with the severity of periodontal disease (P = .02). Survival free of cardiovascular events (94% vs 83%, log-rank 0.009), coronary events (97% vs 89%, log-rank = 0.009), and cardiovascular death (96% vs 87%, log-rank = 0.037) was higher in the evaluated group. Death by any cause did not differ between groups. Multivariate analysis showed that treatment was associated with reduction in cardiovascular events (HR 0.43; 95% CI 0.22-0.87), coronary events (HR 0.31; 95% CI 0.12-0.83), and cardiovascular deaths (HR 0.43; 95% CI 0.19-0.98). CONCLUSION: Periodontal treatment reduced the 24-month incidence of cardiovascular events and cardiovascular death, suggesting that periodontal treatment may improve cardiovascular outcomes. We suggest that periodontal screening and eventual treatment may be considered in patients with advanced renal disease.

Evaluation of a protocol for coronary artery disease investigation in asymptomatic elderly hemodialysis patients.

BACKGROUND: Coronary artery disease (CAD) is prevalent in older patients on dialysis, but the prognostic relevance of coronary assessment in asymptomatic subjects remains undefined. We tested the usefulness of a protocol, based on clinical, invasive, and noninvasive coronary assessment, by answering these questions: Could selecting asymptomatic patients for coronary invasive assessment identify those at higher risk of events? Is CAD associated with a worse prognosis? METHODS: A retrospective study including 276 asymptomatic patients at least 65 years old on the waiting list, prospectively evaluated for CAD and followed up until death or renal transplantation, were classified into two groups: 1) low-risk patients who did not undergo coronary angiography (n=63) and 2) patients who did undergo angiography (n=213). The latter group was reclassified into patients with significant CAD or normal angiograms/nonsignificant CAD. RESULTS: CAD (≥70% stenosis) occurred in 124 subjects (58%). The incidence of death by any cause, coronary death, and major cardiovascular (CV) events were similar in patients selected or not for angiography and in those with or without significant CAD. Myocardial revascularization (surgical/percutaneous) was performed in only 21/276 patients (7.6%) and did not result in a reduction in mortality. CONCLUSION: In older patients on renal replacement therapy, the prevalence of CAD was high, but coronary investigation was not useful as a risk stratification tool and also resulted in a rather small proportion of patients eligible for intervention. Therefore, in the elderly, coronary investigation should not be considered routine in asymptomatic patients.

Coronary Artery Disease Assessment and Intervention in Renal Transplant Patients: Analysis from the KiHeart Cohort.

BACKGROUND: The value of coronary artery disease (CAD) assessment and coronary intervention in the prognosis of patients who undergo renal transplantation is controversial. We investigated whether pretransplant identification of patients with CAD is helpful for defining prognosis and whether preemptive coronary intervention reduces the incidence of cardiovascular events and death after engraftment. METHODS: We analyzed the impact of coronary assessment by clinical stratification and coronary angiography and of coronary intervention on prognosis in 535 chronic kidney disease patients on the transplantation waiting list who underwent renal transplantation. RESULTS: Patients with 70% or greater narrowing experienced more coronary events than patients with less significant lesions (P = 0.01) and subjects at low risk (P = 0.001). Coronary assessment did not discriminate between the risk of death in patients with or without significant CAD, and the independent predictors of death were age (hazards ratio, 1.04; 95% confidence interval, 1.01-1.06, P = 0.001) and diabetes (hazards ratio, 1.63; 95% confidence interval, 1.11-2.39, P = 0.01). No difference occurred in events and mortality between patients treated medically or by intervention, but the severity of CAD was higher in the latter. CONCLUSIONS: Coronary assessment identified patients at increased risk of posttransplant coronary events and was also useful to define a low-risk population that may be safely transplanted without in-depth cardiovascular evaluation. However, it did not differentiate between the risk of death in patients with and those without significant CAD. Survival was similar in patients undergoing either medical or interventional treatment for CAD.

Rationale and benefits of trimetazidine by acting on cardiac metabolism in heart failure.

Heart failure is a systemic and multiorgan syndrome with metabolic failure as a fundamental mechanism. As a consequence of its impaired metabolism, other processes are activated in the failing heart, further exacerbating the progression of heart failure. Recent evidence suggests that modulating cardiac energy metabolism by reducing fatty acid oxidation and/or increasing glucose oxidation represents a promising approach to the treatment of patients with heart failure. Clinical trials have demonstrated that the adjunct of trimetazidine to the conventional medical therapy improves symptoms, cardiac function and prognosis in patients with heart failure without exerting negative hemodynamic effects. This review focuses on the rationale and clinical benefits of trimetazidine by acting on cardiac metabolism in heart failure, and aims to draw attention to the readiness of this agent to be included in all the major guidelines dealing with heart failure.

Coronary events in obese hemodialysis patients before and after renal transplantation.

We examined the impact of obesity (BMI ≥30 kg/m(2) , n = 357) on prognosis in 1696 hemodialysis (HD) patients before and after renal transplantation (TX). End-points were coronary events, composite cardiovascular (CV) events, and death. Obese HD patients were older (55.9 ± 9.2 vs. 54.2 ± 11), had more diabetes (54% vs. 40%), dyslipidemia (49% vs. 30%), altered myocardial scan (38% vs. 31%), myocardial infarction (MI) (16% vs. 10%), coronary intervention (11% vs. 7%), higher total cholesterol (186 ± 52 vs. 169 ± 47), and triglycerides (219 ± 167 vs. 144 ± 91). Obese undergoing TX had more dyslipidemia (46% vs. 31%), angina (23% vs. 14%), MI (18% vs. 5%), increased total cholesterol (185 ± 56 vs. 172 ± 48), and triglycerides (237 ± 190 vs. 149 ± 100). Obesity was independently associated with coronary events (log-rank = 0.008, HR 2.55% CI 1.27-5.11) and death (log-rank 0.046, HR 1.52, % CI 1.007-2.30) in TX but not in HD. Obese HD patients had more risk factors and ischemic heart disease, but these characteristics did not interfere with prognosis. In TX patients, obesity predicts coronary events and death.

Prognostic Value of Serum Uric Acid in Patients on the Waiting List before and after Renal Transplantation.

Background. High serum uric acid (UA) is associated with increased cardiovascular (CV) risk in the general population. The impact of UA on CV events and mortality in CKD is unclear. Objective. To assess the relationship between UA and prognosis in hemodialysis (HD) patients before and after renal transplantation (TX). Methods. 1020 HD patients assessed for CV risk and followed from the time of inception until CV event, death, or TX (HD) or date of TX, CV event, death, or return to dialysis (TX). Results. 821 patients remained on HD while 199 underwent TX. High UA (≥428 mmol/L) was not associated with either composite CV events or mortality in HD patients. In TX patients high UA predicted an increased risk of events (P = 0.03, HR 1.6, and 95% CI 1.03-2.54) but not with death. In the Cox proportional model UA was no longer significantly associated with CV events. Instead, a reduced GFR (<50 mL/min) emerged as the independent risk factor for events (P = 0.02, HR 1.79, and % CI 1.07-3.21). Conclusion. In recipients of TX an increased posttransplant UA is related to higher probability of major CV events but this association probably caused concurrent reduction in GFR.

Incremental prognostic value of kidney function decline over coronary artery disease for cardiovascular event prediction after coronary computed tomography.

It is unknown whether mild chronic kidney disease (CKD) is associated with adverse cardiovascular (CV) prognosis after accounting for coronary artery disease (CAD). Here we evaluated the interplay between CKD and CAD in predicting CV death or myocardial infarction (MI) and all-cause death. We included 1541 consecutive patients in the Partners registry (mean age 55 years, 43% female) over 18 years old with no known prior CAD who underwent coronary computed tomography angiography (CCTA). The results of CCTA were categorized as normal, nonobstructive (under half), or obstructive (half and over). Overall, 653 of the patients had no CAD, 583 had nonobstructive CAD, and 305 had obstructive CAD, while 1299 had eGFR over 60 ml/min per 1.73 m(2) and 242 had an eGFR under this value. The presence and severity of CAD was significantly associated with an increased rate of CV death or MI and all-cause death, even after adjustment for age, gender, symptoms, and risk factors. Similarly, reduced eGFR was significantly associated with CV death or MI and all-cause death after similar adjustment. The addition of reduced GFR to a model which included both clinical variables and CCTA findings resulted in significant improvement in the prediction of CV death or MI and all-cause death. Thus, among individuals referred for CCTA to evaluate CAD, renal dysfunction is associated with an increased rate of CV events, mainly driven by an increase in the rate of noncoronary CV events. In this group of patients, both eGFR and the presence and severity of CAD together improve the prediction of future CV events and death.

High dose of N-acetylcystein prevents acute kidney injury in chronic kidney disease patients undergoing myocardial revascularization.

BACKGROUND: The renoprotective effect of N-acetylcystein in patients undergoing coronary artery bypass graft surgery is controversial. METHODS: We assessed the renoprotective effect of the highest dose of N-acetylcystein sanctioned for clinical use in a prospective, double-blind, placebo-controlled study including 70 chronic kidney disease patients, stage 3 or 4, who underwent coronary artery bypass graft surgery, on cardiopulmonary bypass (CPB) and off CPB, and were randomly allocated to receive either N-acetylcystein 150 mg/kg followed by 50 mg/kg for 6 hours in 0.9% saline or only 0.9% saline. Acute kidney injury was defined by the Acute Kidney Injury Network classification. RESULTS: The incidence of kidney injury was reduced in the N-acetylcystein group (57.1% versus 28.6%, p=0.016). Nonuse of N-acetylcystein (relative risk 3.58, 95% confidence interval: 1.04 to 12.33, p=0.04) and cardiopulmonary bypass (relative risk 4.55, 95% confidence interval: 1.28 to 16.15, p=0.02) were independent predictors of kidney injury. In patients treated with CPB, N-acetylcystein reduced the incidence of kidney injury from 63% to 46%. Oxidative stress was increased in control subjects (p=0.01) and abolished in patients receiving N-acetylcystein. CONCLUSIONS: Maximum intravenous doses of N-acetylcystein reduce the incidence of acute kidney injury in patients with kidney disease undergoing coronary artery bypass graft surgery, abolish oxidative stress, and mitigate the negative effect of CPB on renal function.

Prognostic value of nonobstructive and obstructive coronary artery disease detected by coronary computed tomography angiography to identify cardiovascular events.

BACKGROUND: The contribution of plaque extent to predict cardiovascular events among patients with nonobstructive and obstructive coronary artery disease (CAD) is not well defined. Our objective was to evaluate the prognostic value of plaque extent detected by coronary computed tomography angiography. METHODS AND RESULTS: All consecutive patients without prior CAD referred for coronary computed tomography angiography to evaluate for CAD were included. Examination findings were classified as normal, nonobstructive (<50% stenosis), or obstructive (≥50%). Based on the number of segments with disease, extent of CAD was classified as nonextensive (≤4 segments) or extensive (>4 segments). The cohort included 3242 patients followed for the primary outcome of cardiovascular death or myocardial infarction for a median of 3.6 (2.1-5.0) years. In a multivariable analysis, the presence of extensive nonobstructive CAD (hazard ratio, 3.1; 95% confidence interval, 1.5-6.4), nonextensive obstructive (hazard ratio, 3.0; 95% confidence interval, 1.3-6.9), and extensive obstructive CAD (hazard ratio, 3.9; 95% confidence interval, 2.2-7.2) were associated with an increased rate of events, whereas nonextensive, nonobstructive CAD was not. The addition of plaque extent to a model that included clinical probability as well as the presence and severity of CAD improved risk prediction. CONCLUSIONS: Among patients with nonobstructive CAD, those with extensive plaque experienced a higher rate of cardiovascular death or myocardial infarction, comparable with those who have nonextensive disease. Even among patients with obstructive CAD, greater extent of nonobstructive plaque was associated with higher event rate. Our findings suggest that regardless of whether obstructive or nonobstructive disease is present, the extent of plaque detected by coronary computed tomography angiography enhances risk assessment.