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.

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.

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.

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.

Obstructive sleep apnea is associated with interdialytic weight gain and increased long-term cardiovascular events in hemodialysis patients.

BACKGROUND: Obstructive sleep apnea (OSA) is common in hemodialysis (HD) patients. The reasons for the high prevalence and whether OSA is associated with vascular impairment, end-organ damage, and prognosis are not completely clear. METHODS: We evaluated patients with low cardiovascular risk on HD, not treated by CPAP. Laboratory tests, sleep questionnaires (Berlin and Epworth) and polysonography studies, echocardiography, and markers of arterial stiffness and atherosclerosis were performed. After the initial evaluation, patients were followed up until cardiovascular events, renal transplantation, or death. RESULTS: Fifty-five patients (49% male, 50 ± 9 years, body mass index 24.7 ± 4.5 kg/m2) were included. OSA (apnea-hypopnea index ≥ 5 events/h) occurred in 73% of the patients. The proportion of patients with interdialytic weight gain > 2 kg was higher in patients with OSA than those without OSA (96 vs. 55%; p = 0.002). Left ventricular (LV) posterior wall thickness (10.0 ± 1.9 vs. 11.3 ± 1.8 mm; p = 0.04) and LV diastolic diameter (48 ± 5 vs. 53 ± 5 mm; p = 0.003) were higher in patients with OSA than in patients without OSA, respectively. Sleep questionnaires did not predict OSA. No significant differences were found in pulse wave velocity, carotid intima-media thickness, and ankle-brachial index between the groups. Multivariate analysis showed that interdialytic weight gain > 2 kg and LV diastolic diameter were independently associated with OSA. On follow-up (median 45 months), OSA was found to be associated with a higher incidence of cardiovascular (CV) events (28 vs. 7%, log-rank = 0.042). CONCLUSIONS: OSA was associated with increased risk of CV events. Significant (> 2 kg) interdialytic weight gain was independently associated with OSA.

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.

Myocardial scintigraphy and clinical stratification as predictors of events in renal transplant candidates.

BACKGROUND: We tested the hypothesis that the universal application of myocardial scanning with single-photon emission computed tomography (SPECT) would result in better risk stratification in renal transplant candidates (RTC) compared with SPECT being restricted to patients who, in addition to renal disease, had other clinical risk factors. METHODS: RTCs (n=363) underwent SPECT and clinical risk stratification according to the American Society of Transplantation (AST) algorithm and were followed up until a major adverse cardiovascular event (MACE) or death. RESULTS: Of the 363 patients, 79 patients (22%) had an abnormal SPECT scan and 270 (74%) were classified as high risk. Both methods correctly identified patients with increased probability of MACE. However, clinical stratification performed better (sensitivity and negative predictive value 99% and 99% vs. 25% and 87%, respectively). High-risk patients with an abnormal SPECT scan had a modest increased risk of events (log-rank = 0.03; hazard ratio [HR] = 1.37; 95% confidence interval [95% CI], 1.02-1.82). Eighty-six patients underwent coronary angiography, and coronary artery disease (CAD) was found in 60%. High-risk patients with CAD had an increased incidence of events (log-rank = 0.008; HR=3.85; 95% CI, 1.46-13.22), but in those with an abnormal SPECT scan, the incidence of events was not influenced by CAD (log-rank = 0.23). Forty-six patients died. Clinical stratification, but not SPECT, correlated with the probability of death (log-rank = 0.02; HR=3.25; 95% CI, 1.31-10.82). CONCLUSION: SPECT should be restricted to high-risk patients. Moreover, in contrast to SPECT, the AST algorithm was also useful for predicting death by any cause in RTCs and for selecting patients for invasive coronary testing.

Treatment of coronary artery disease in hemodialysis patients evaluated for transplant-a registry study.

BACKGROUND: We assessed the results of a noninvasive therapeutic strategy on the long-term occurrence of cardiac events and death in a registry of patients with chronic kidney disease (CKD) and coronary artery disease (CAD). METHODS: We analyzed 519 patients with CKD (56+/-9 years, 67% men, 67% whites) on maintenance hemodialysis with clinical or scintigraphic evidence of CAD by using coronary angiography. RESULTS: In 230 (44%) patients, coronary angiography revealed significant CAD (lumen reduction > or =70%). Subjects with significant CAD were kept on medical treatment (MT; n=184) or referred for myocardial revascularization (percutaneous transluminal coronary angioplasty/coronary artery bypass graft-intervention; n=30) according to American College of Cardiology/American Heart Association guidelines. In addition, 16 subjects refused intervention and were also followed-up. Event-free survival for patients on MT at 12, 36, and 60 months was 86%, 71%, and 57%, whereas overall survival was 89%, 71%, and 50% in the same period, respectively. Patients who refused intervention had a significantly worse prognosis compared with those who actually underwent intervention (events: hazard ratio=4.50; % confidence interval=1.48-15.10; death: hazard ratio=3.39; % confidence interval 1.41-8.45). CONCLUSIONS: In patients with CKD and significant CAD, MT promotes adequate long-term event-free survival. However, failure to perform a coronary intervention when necessary results in an accentuated increased risk of events and death.

Cardiac MRI for detection of unrecognized myocardial infarction in patients with end-stage renal disease: comparison with ECG and scintigraphy.

OBJECTIVE: The purposes of this study were to use the myocardial delayed enhancement technique of cardiac MRI to investigate the frequency of unrecognized myocardial infarction (MI) in patients with end-stage renal disease, to compare the findings with those of ECG and SPECT, and to examine factors that may influence the utility of these methods in the detection of MI. SUBJECTS AND METHODS: We prospectively performed cardiac MRI, ECG, and SPECT to detect unrecognized MI in 72 patients with end-stage renal disease at high risk of coronary artery disease but without a clinical history of MI. RESULTS: Fifty-six patients (78%) were men (mean age, 56.2 +/- 9.4 years) and 16 (22%) were women (mean age, 55.8 +/- 11.4). The mean left ventricular mass index was 103.4 +/- 27.3 g/m(2), and the mean ejection fraction was 60.6% +/- 15.5%. Myocardial delayed enhancement imaging depicted unrecognized MI in 18 patients (25%). ECG findings were abnormal in five patients (7%), and SPECT findings were abnormal in 19 patients (26%). ECG findings were false-negative in 14 cases and false-positive in one case. The accuracy, sensitivity, and specificity of ECG were 79.2%, 22.2%, and 98.1% (p = 0.002). SPECT findings were false-negative in six cases and false-positive in seven cases. The accuracy, sensitivity, and specificity of SPECT were 81.9%, 66.7%, and 87.0% (not significant). During a period of 4.9-77.9 months, 19 cardiac deaths were documented, but no statistical significance was found in survival analysis. CONCLUSION: Cardiac MRI with myocardial delayed enhancement can depict unrecognized MI in patients with end-stage renal disease. ECG and SPECT had low sensitivity in detection of MI. Infarct size and left ventricular mass can influence the utility of these methods in the detection of MI.

Parathyroidectomy reduces cardiovascular events and mortality in renal hyperparathyroidism.

BACKGROUND: Secondary hyperparathyroidism (SHPT) and its associated abnormalities in mineral metabolism increase the risk of cardiovascular morbidity and death in chronic renal failure (CRF). The effect of parathyroidectomy (PTX) on the incidence of major cardiovascular events in CRF patients with SHPT is unknown. We tested the hypothesis that PTX reduces the incidence of cardiovascular complications and death in CRF patients with severe SHPT scheduled for PTX, comparing the outcome of patients treated or not treated by PTX. METHODS: The study comprised 118 CRF patients with SHPT on maintenance hemodialysis, unresponsive to medical treatment and scheduled for PTX. Patients underwent comprehensive cardiovascular evaluations at baseline. They were followed up until death, occurrence of major cardiovascular events, or kidney transplantation. RESULTS: No deaths related to PTX occurred. After a median follow-up of 30 months, 50 patients (42%) had undergone PTX whereas 68 (58%) had not. The groups were comparable in terms of age, sex, race, serum parathyroid hormone, calcium or phosphate, calcium x phosphate product, and all major cardiovascular variables, except diastolic blood pressure. PTX was associated with a reduced incidence of major cardiovascular events (P = .02) and overall mortality (P

Screening for significant coronary artery disease in high-risk renal transplant candidates.

BACKGROUND: Renal transplant candidates are at an increased risk for coronary artery disease (CAD), a strong predictor of cardiovascular events [major adverse coronary events (MACE)]. Coronary angiography is a costly, risky, invasive procedure. We sought to determine clinical predictors of significant CAD (stenosis > or =70%) in high-risk renal transplant candidates. METHODS: Clinical evaluation and coronary angiography were performed in 301 patients (57+/-8 years, 73% men) on hemodialysis for 32 months (median). Patients were followed-up for 22 months (median). Inclusion criteria were diabetes (type 1 or 2), evidence of cardiovascular disease, or age > or =50 years. Risk factors included hypertension (93.7%), overweight/obesity (54.3%), dyslipidemia (44.9%), diabetes (42.1%), and smoking (24.3%). Cardiovascular disease was found as follows: peripheral arterial disease (PAD) (31.2%), angina (28.1%), stroke (12.9%), myocardial infarction (MI) (10.3%), and heart failure (9.3%). RESULTS: Significant CAD was found in 136 individuals (45.2%). Diabetes [odds ratio (OR)=1.82; 95% confidence interval (CI)=1.08-3.07], PAD (OR=2.50; 95% CI=1.44-4.37), and previous MI (OR=7.75; 95% CI=3.03-23.98) were associated with significant CAD. The prevalence of significant CAD increased with the number of clinical predictors from 26% (none) to 100% (all present) (P<0.0001). The incidence of fatal/nonfatal MACE increased two, four, and sixfold in those with diabetes, PAD, or previous MI, respectively (P<0.0001). CONCLUSIONS: In high-risk patients with end-stage renal disease, the prevalence of CAD and the incidence of MACE were high. Significant CAD or cardiovascular complications were not related to the majority of classic risk factors. Patients with diabetes, PAD, or previous MI are at higher risk of CAD, MACE, or both and, thus, must be referred for invasive diagnostic procedures.

Coronary angiography is the best predictor of events in renal transplant candidates compared with noninvasive testing.

Guidelines for the detection of coronary artery disease (CAD) and assess of risk in renal transplant candidates are based on the results of noninvasive testing, according to data originated in the nonuremic population. We evaluated prospectively the accuracy of 2 noninvasive tests and risk stratification in detecting CAD (>or=70% obstruction) and assessing cardiac risk by using coronary angiography (CA). One hundred twenty-six renal transplant candidates who were classified as at moderate (>or=50 years) or high (diabetes, extracardiac atherosclerosis, or clinical coronary artery disease) coronary risk underwent myocardial scintigraphy (SPECT), dobutamine stress echocardiography, and CA and were followed for 6 to 48 months. The prevalence of CAD was 42%. The sensitivities and negative predictive values for the 2 noninvasive tests and risk stratification were <75%. After 6 to 48 months, there were 18 cardiac events, 9 fatal. Risk stratification (P=0.007) and CA (P=0.0002) predicted the crude probability of surviving free of cardiac events. The probability of event-free survival at 6, 12, 24, 36, and 48 months were 98%, 98%, 94%, 94%, and 94% in patients with <70% stenosis on CA and 97%, 87%, 61%, 56%, and 54% in patients with >or=70% stenosis. Multivariate analysis showed that the sole predictor of cardiac events was critical coronary lesions (P=0.003). Coronary angiography may still be necessary for detecting CAD and determining cardiac risk in renal transplant candidates. The data suggest that current algorithms based on noninvasive testing in this population should be revised.

Twenty-four hour blood pressure profile and left ventricular hypertrophy early after renal transplantation.

BACKGROUND: Left ventricular hypertrophy is common in renal transplant patients but the factors influencing its development remain to be determined. The present investigation was conducted to study the effect of blood pressure load on the left ventricular mass of recently transplanted patients using 24-h ambulatory blood pressure monitoring (ABPM). METHODS: We studied 30 renal transplant (RT) patients (36.1+/-13.7 years old, 11 males, 26 Whites, 4 diabetics, 15 under antihypertensive medication, 21 recipients of cadaver donors, and all treated with steroids, cyclosporin and azathioprine and with adequate (serum creatinine < 1.8 mg/100 ml) renal function). The median duration of dialysis treatment before transplant was 37 months, and the studies were performed during the first 40 days post-transplantation. Blood pressure was measured after a 15-min rest (casual blood pressure) and during a 24-h period with a SpaceLabs apparatus. Echocardiograms were obtained from all patients. RESULTS: Mean left ventricular mass index (LVMI) was 153+/-44 g/m2; casual systolic and diastolic BP (mmHg) was 152+/-25 and 92+/-13, whereas systolic and diastolic 24-h BP was 133+/-12 and 85+/-8, respectively. The systolic sleeping BP/awake systolic BP (SSBP/ASBP) ratio was 0.94+/-0.07, and 73% of the patients did not show a significant (>10%) fall of systolic blood pressure during sleep. Multivariate analysis showed that awake systolic blood pressure was the only variable that independently influenced LVMI after adjusting for confounding factors (regression coefficient = 0.49, p = 0.01). Casual systolic and diastolic BP, sleeping systolic and diastolic blood pressure, 24-h heart rate, age, race, gender, smoking, body mass index, duration of dialysis, diabetes, antihypertensive and immunosuppressive drugs and levels of hematocrit, creatinine and serum lipids did not correlate with LVMI. CONCLUSION: The data indicate that left ventricular hypertrophy during the early post-transplant period is mainly influenced by awake blood pressure load. They also suggest that ABPM may be more useful in the diagnosis and management of post-transplant hypertension than casual BP. The findings emphasize the importance of rigid blood pressure control in renal transplant recipients.

Long-term impact of renal transplantation on carotid artery properties and on ventricular hypertrophy in end-stage renal failure patients.

BACKGROUND: The aim of this study was to examine prospectively the impact of renal transplantation on the morphological and functional characteristics of the carotid arteries and heart in a group of end-stage renal failure patients without overt cardiovascular disease, followed up for >3 years. METHODS: Twenty-two patients were evaluated 2-3 weeks after renal transplantation, and again 12 and 40 months post-transplant, using high resolution ultrasound imaging and echocardiography. RESULTS: Kidney and patient survival were 100% at the end of follow-up without any major cardiovascular events. After 40+/-1.2 months, carotid morphological parameters were normalized: carotid intima-media thickness fell from 788+/-24 to 676+/-32 microm (P<0.01) and the carotid wall/lumen ratio fell from 118+/-3 to 103+/-3 microm (P<0.01). Significant reduction of left ventricular (LV) posterior wall thickness (11.5+/-0.2 to 11.3+/-0.2 mm, P<0.05) and LV mass index (172+/-9 to 158+/-8 g/m(2), P<0.01) was already observed after 12+/-0.2 months. Further reduction of LV posterior wall thickness (10.4+/-0.3 mm, P<0.01) and of LV mass index (136+/-7 g/m(2), P<0.01) also occurred after 40+/-1.2 months. However, carotid distensibility (19.5+/-2.1 vs 22+/-2.4, not significant (NS)) and LV compliance (early to atrial flow ratio: 1.2+/-0.1 vs 1.3+/-0.1, NS) remained abnormal, and normalization of the LV mass was attained by only 25% of the patients with LV hypertrophy on baseline. Multiple stepwise regression analysis showed that the rate of change of reduction of the intima-media thickness was influenced by age (negative association, P<0.001) and was positively related to white race (P<0.05), female sex (P<0.01) and to the parallel reduction of maximum carotid diameter (P<0.001). Reduction of LV mass index over time was negatively related to the duration of dialysis treatment and to the parallel increase observed in body mass index and haematocrit, and was positively related to the simultaneous reduction of diastolic blood pressure (P<0.01 for all variables). CONCLUSIONS: Successful renal transplantation improves but does not cause complete regression of the cardiovascular alterations of end-stage renal disease. Only intima-media thickness was normalized by transplantation, whereas LVMI and carotid and ventricular distensibility remained abnormal. The results suggest that extended duration of dialysis, weight gain, high blood pressure and high haematocrit may adversely affect the rate of change of post-transplant cardiovascular hypertrophy.