Independent and additive impact of blood pressure control and angiotensin II receptor blockade on renal outcomes in the irbesartan diabetic nephropathy trial: clinical implications and limitations

Elevated arterial pressure is a major risk factor for progression to ESRD in diabetic nephropathy. However, the component of arterial pressure and level of BP control for optimal renal outcomes are disputed. Data from 1590 hypertensive patients with type 2 diabetes in the Irbesartan Diabetic Nephropathy Trial (IDNT), a randomized, double-blind, placebo-controlled trial performed in 209 clinics worldwide, were examined, and the effects of baseline and mean follow-up systolic BP (SBP) and diastolic BP and the interaction of assigned study medications (irbesartan, amlodipine, and placebo) on progressive renal failure and all-cause mortality were assessed. Other antihypertensive agents were added to achieve predetermined BP goals. Entry criteria included elevated baseline serum creatinine concentration up to 266 micromol/L (3.0 mg/dl) and urine protein excretion >900 mg/d. Baseline BP averaged 159/87 +/- 20/11 mmHg. Median patient follow-up was 2.6 yr. Follow-up achieved SBP most strongly predicted renal outcomes. SBP >149 mmHg was associated with a 2.2-fold increase in the risk for doubling serum creatinine or ESRD compared with SBP <134 mmHg. Progressive lowering of SBP to 120 mmHg was associated with improved renal and patient survival, an effect independent of baseline renal function. Below this threshold, all-cause mortality increased. An additional renoprotective effect of irbesartan, independent of achieved SBP, was observed down to 120 mmHg. There was no correlation between diastolic BP and renal outcomes. We recommend a SBP target between 120 and 130 mmHg, in conjunction with blockade of the renin-angiotensin system, in patients with type 2 diabetic nephropathy.     

Associations between home blood pressure and mortality in peritoneal dialysis

Objective To investigate the association between the home blood pressure (BP) and morality in peritoneal dialysis (PD). Methods PD patients from the First Affiliated Hospital of Zhejiang University from January 1, 2008 to June 30, 2016 were studied. Over the first 6 months PD therapy, systolic SB (SBP) and diastolic BP (DBP) averaged as 5 (＜120 to≥150 mmHg in 10 mmHg increments) and 4 (＜70 to≥90 mmHg in 10 mmHg increments) categories, respectively, as well as continuous measures. All-cause and cardiovascular mortality were assessed by using Cox regression models adjusted for demographics, laboratory measurements, comorbid conditions and antihypertensive medications. The relationships between home BP and all-cause and cardiovascular mortality were assessed by restricted cubic spline regression model. Results A total of 1663 PD patients were included with a median follow-up of 29.9 months, in which 737 patients (44.3%) were female. The SBP and DBP were (135.2±15.8) mmHg and (83.1±10.5) mmHg, respectively. Two hundred and twenty-one PD patients died during the study period, of which 102 patients (46.2%) died of cardiac-cerebral vascular events. With 130≤SBP＜140 mmHg as a refernece, SBP≥150 mmHg (HR=1.83, 95%CI 1.19-2.82, P=0.005) and SBP＜120 mmHg (HR=2.05, 95%CI 1.29-3.27, P＜0.001) were associated with significantly higher risks of all-cause morality, but not cardiovascular morality. With 80≤DBP＜90 mmHg as a refernece, patients with DBP≥90 mmHg exhibited significantly higher risks of all-cause mortality (HR=1.80, 95%CI 1.21-2.68, P=0.009). SBP presented a U-shaped association with all-cause mortality. DBP presented a J-shaped association with all-cause mortality. Conclusions Higher SBP, lower SBP and higher DBP are associated with higher risks of all-cause mortality in PD patients. However, neither SBP nor DBP is observed statistically significant relationship with the risk of cardiovascular mortality. Further prospective and randomized clinical trials are needed to determine the optimal BP targets and improve the management of hypertension in PD patients.     

The association between BP and mortality in patients on chronic peritoneal dialysis.

BACKGROUND: The relationship between blood pressure (BP) and mortality in haemodialysis patients is unconventional. It is not clear if this is the consequence of uraemia or related to the dialysis type. The goal of this project was to identify the relationship between BP and mortality in patients on chronic peritoneal dialysis (PD). METHODS: Patients on PD (n = 1053) from the USRDS prospective DMMS Wave 2 study were analysed. Primary outcomes were all-cause and cardiovascular mortality and duration of hospitalization. RESULTS: Low systolic BP categories, <100 mmHg [hazard ratio (HR), 2.71, P<0.001; and HR 3.83, P<0.001, respectively] and 101-110 mmHg (HR 1.85, P<0.05; and HR 2.92, P<0.005, respectively), but not high systolic BP, increased the risk of all-cause and cardiovascular mortality, with systolic BP 111-120 mmHg as the reference. Pulse BP, but not diastolic BP, followed a similar trend. In subgroup analysis, this association was demonstrated only in patients with a history of heart failure, in patients with diabetes and in those treated with antihypertensive medications. CONCLUSION: Systolic BP <111 mmHg in PD patients is associated with higher mortality risk, while systolic BP >120 mmHg is associated with fewer hospital days. Aggressive treatment of hypertension in the PD population should be cautioned.     

BP,Cardiovascular Disease,and Death in the Folic Acid for Vascular Outcome Reduction in Transplantation Trial

The optimal BP level in kidney transplant recipients remains uncertain. This post hoc analysis of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial cohort assessed associations of BP with a pooled cardiovascular disease (CVD) outcome and with all-cause mortality. In 3474 prevalent kidney transplant patients, mean age was 52±9 years, 63% were men, 76% were white, 20% had a history of CVD, 40% had a history of diabetes mellitus, and the median time since transplant was 4.1 years (25th to 75th percentiles, 1.7–7.4); mean systolic BP was 136±20 mmHg and mean diastolic BP was 79±12 mmHg. There were 497 CVD events and 406 deaths. After adjustment for demographic and transplant characteristics and CVD risk factors, each 20-mmHg increase in baseline systolic BP associated with a 32% increase in subsequent CVD risk (hazard ratio [HR], 1.32; 95% confidence interval [95% CI], 1.19 to 1.46) and a 13% increase in mortality risk (HR, 1.13; 95% CI, 1.01 to 1.27). Similarly, after adjustment, at diastolic BP levels<70 mmHg, each 10-mmHg decrease in diastolic BP level associated with a 31% increase in CVD risk (HR, 1.31; 95% CI, 1.06 to 1.62) and a 31% increase in mortality risk (HR, 1.31; 95% CI, 1.03 to 1.66). However, at diastolic BP levels>70 mmHg, there was no significant relationship between diastolic BP and outcomes. Higher systolic BP strongly and independently associated with increased risk of CVD and all-cause mortality, without evidence of a J shape, whereas only lower levels of diastolic BP associated with increased risk of CVD and death in this trial.     

The relationship between changes of blood pressure during dialysis and mortality in maintenance hemodialysis patients

Objective To determine the relationship between changes of blood pressure (BP) during dialysis and mortality in maintenance hemodialysis (MHD) patients. Methods A total of 364 cases of MHD patients were collected prospectively and the relationship between changes of blood pressure during dialysis and mortality was assessed. Results The patients' age was (63.07±13.93) years. Over a follow-up of (54.86±19.84) months, a total of 85 (23.4%) all-cause and 46(12.6%) cardiovascular deaths occurred. Post-dialytic drops in systolic BP between 7.08 mmHg and 14.25 mmHg were associated with lower all-cause and cardiovascular mortality [OR=0.324 and 0.335, 95%CI (0.152, 0.692) and (0.123, 0.911), P=0.004 and 0.032, respectively]. Kaplan-Meier analysis showed that post-dialytic increase in systolic BP more than 0.25 mmHg was associated with higher all-cause and cardiovascular mortality (P=0.001, 0.044, respectively). Multivariate logistic regression analysis showed that post-dialytic increase in systolic BP more than 0.25 mmHg, hemoglobin, Kt/V were independent risk factors for all-cause mortality. Conclusions Post-dialytic increase in systolic BP more than 0.25 mmHg in MHD patients suggests higher mortality. Significant increased systolic BP after hemodialysis, hemoglobin level and Kt/V were independent risk factors for all-cause mortality.     

Treating hypertension in the patient with overt diabetic nephropathy

Arterial blood pressure is a major determinant of renal and cardiovascular outcomes in diabetic nephropathy. There is a proportional relationship between the systolic blood pressure and renal and mortality outcomes. Decreasing the diastolic pressure does not significantly decrease these outcomes. Irrespective of the magnitude of pretreatment systolic hypertension in the patient with type 2 diabetic nephropathy, the systolic pressure achieved with antihypertensive therapy is the important determinant of renal and cardiovascular risk. Achieving a lower systolic pressure down to 120 mm Hg is associated with substantial risk reduction. Although the data are limited, systolic blood pressure less than 120 mm Hg may be associated with increased all-cause mortality in this patient population, increasing the possibility of a J-curve response. A marked decrease in diastolic pressure, which is a danger when undertaking aggressive therapy with the goal of decreasing the systolic pressure to 130 mm Hg, can be associated with an increased risk of cardiac events. The renoprotective and proteinuria-decreasing effects of angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers recommend these agents as the standard of care in type 2 diabetic nephropathy. In addition to angiotensin-converting enzyme inhibitor and angiotensin-receptor blocker therapy, controlling the systolic blood pressure in this difficult to control patient population may require the use of 3 or more antihypertensive agents.     

Hypertension and survival in hemodialysis patients

Hypertension is clearly an independent risk factor for cardiovascular (CV) events and death in the general population, but the relationship between blood pressure (BP) and survival in dialysis patients is less clear. In dialysis populations at lower risk of CV events, BP is directly related to survival, while in those with high risk, it has been difficult to show such an effect. The effects of cardiac disease complicate the relationship between BP and outcome. Retrospective studies of large cohorts, with high prevalence of CV disease, have shown a U-shaped relationship between both systolic and diastolic BP and outcome. These findings probably reflect a high prevalence of cardiac failure and thus high mortality associated with low BP (i.e., a so-called reverse causation). Pulse pressure (high systolic BP and low diastolic BP) predicts outcome in hypertensive dialysis patients. Whether this reflects advanced vessel wall disease or is an independent etiologically significant risk factor is unclear. However, the current uncertainties as to the exact relationship between BP and outcome in dialysis patients do not warrant complacency regarding the prevention and treatment of hypertension.     

Changing relationship of blood pressure with mortality over time among hemodialysis patients

High BP is a major risk factor for atherosclerotic cardiovascular disease mortality in the general population. Surprising, studies that have been conducted among hemodialysis (HD) patients have yielded conflicting data on the relationship between BP and mortality. This study explores two hypotheses among HD patients: (1) The relationship between BP and mortality changes over time, and (2) mild to moderate hypertension is well tolerated. Incident HD patients who were treated at Dialysis Clinic Inc. facilities between 1993 and 2003 were studied. Primary end points were atherosclerotic cardiovascular disease and all-cause mortality. The relationship between BP and mortality was analyzed in two sets of Cox proportional hazards models. Model-B explored the relationship between baseline BP and mortality in sequential time periods. Model-TV assessed the relationship between BP, treated as time-varying, and mortality. The study sample (n = 16,959) was similar in characteristics to the United States Renal Data Systems population, although black patients were slightly overrepresented. Model-B demonstrated that the relationship between baseline BP and mortality changes over time. Low systolic BP (<120 mmHg) was associated with increased mortality in years 1 and 2. High systolic BP (> or =150 mmHg) was associated with increased mortality among patients who survived > or =3 yr. Low pulse pressure was associated with increased mortality. Model-TV demonstrated that mild to moderate systolic hypertension may be relatively well tolerated. In conclusion, the relationship between baseline BP and mortality changes over time. Mild to moderate systolic hypertension was associated with only modest increases in mortality.     

Nocturnal blood pressure and 24-hour pulse pressure are potent indicators of mortality in hemodialysis patients

BACKGROUND: Cardiovascular (CV) complications are the leading cause of mortality in hemodialysis patients. The role of arterial hypertension on the prognosis of CV in hemodialysis patients is not as clear as in the general population. The purpose of this study was to investigate the prognostic role of ambulatory blood pressure (BP) on CV mortality in treated hypertensive hemodialysis patients. METHODS: Fifty-seven treated hypertensive hemodialysis patients (56.87 +/- 16.22 years, 30 men) were prospectively studied. All patients initially underwent an ambulatory BP monitoring between two dialysis sessions. The outcome event studied was CV death; kidney transplantation and deaths not related to CV disease were censored. RESULTS: The duration of follow-up was 34.4 +/- 20.39 months, during which 10 CV and 8 non-CV fatal events occurred. In the 10 patients who died from CV complications, age, previous CV events, ambulatory systolic BP, ambulatory pulse pressure (PP), and life-long smoking level were significantly higher, and the office diastolic BP was lower at the time of inclusion than in those who did not die from CV complications (N = 47). Based on Cox analysis and after adjustment for age, sex, and previous CV events, a low office diastolic BP [relative risk (RR) 0.49, 95% CI, 0.25 to 0.93, P = 0.03], an elevated 24-hour PP (RR 1.85, 95% CI, 1.28 to 2.65, P = 0.009), and an elevated nocturnal systolic BP (RR 1.41, 95% CI, 1.08 to 1.84, P = 0.01) were predictors of CV mortality (RR associated with a 10 mm Hg increase in BP and in PP). CONCLUSION: This study demonstrates that nocturnal BP and 24-hour PP are independent predictors of CV mortality in treated hypertensive hemodialysis patients. Randomized trials are needed to investigate whether nocturnal BP and 24-hour PP are superior to office BP as targets for antihypertensive therapy in this high-risk group.     

Predialysis blood pressure and mortality risk in a national sample of maintenance hemodialysis patients.

The role of predialysis blood pressure (BP) as a risk factor for the high mortality in chronic hemodialysis (HD) patients has remained controversial. The objective of the current study was to further explore in a national random sample of 4,499 US hemodialysis patients any relationship of systolic or diastolic and predialysis or postdialysis BP with mortality, while considering subgroups of patients and controlling for other patient characteristics and comorbidities. The main finding of this study is the association of a low predialysis systolic BP with an elevated adjusted mortality risk (relative mortality risk [RR] = 1.86 for systolic BP < 110, P < 0.0001). No association with an elevated mortality risk could be observed for predialysis systolic hypertension (RR = 0.98 to 0.99, not significant [NS]), except for an elevated risk of cerebrovascular deaths. Postdialysis systolic BP was associated with an elevated mortality risk both for low and high BP levels as compared with midrange BP. Further evaluation of the elevated mortality risk associated with low predialysis systolic BP indicated similar patterns for both diabetic and nondiabetic subgroups and for patients with and without congestive heart failure (CHF) or coronary artery disease, although it was more pronounced among those with CHF. The level of predialysis fluid excess did not modify these results substantially. The findings from this historical prospective national study do not argue against the treatment of hypertension and suggest greater attention to postdialysis hypertension. The strikingly elevated mortality risk with low predialysis systolic BP suggests that low predialysis BP needs to be viewed with great concern and avoided where possible.     

Salt-sensitive blood pressure--an intermediate phenotype predisposing to diabetic nephropathy?

BACKGROUND: Family studies point to important genetic determinants of diabetic nephropathy (DN). Blood pressure (BP) is higher in offspring of patients with type 2 diabetes and DN, but the pathomechanisms involved have not been elucidated. METHODS: We examined the salt sensitivity of BP after 5 days equilibration on a low (20 mmol/day) vs high salt diet (220 mmol/day) in three matched groups of 15 subjects each: (i) control individuals; (ii) offspring of type 2 diabetic parents without DN (DN-); and (iii) offspring of type 2 diabetic parents with DN (DN+). Ambulatory BP and hormones involved in sodium homeostasis [plasma renin activity (PRA), aldosterone and atrial natriuretic peptide (ANP)] as well as the tetrahydrocortisol + 5-allotetrahydrocortisol/tetrahydrocortisone (THF + 5alphaTHF)/THE) ratio in the urine as an index of 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) activity were analysed. RESULTS: In offspring of DN+ patients on a high salt diet, systolic and diastolic BP was 137/82+/-10/8 mmHg vs 125/77+/-12/8 mmHg in offspring of DN- patients (P<0.01 for systolic BP). The salt-induced difference in mean BP between high and low salt diet was 5.2+/-3.3 mmHg in offspring of DN+ patients vs 0.7+/-4.7 mmHg in offspring of DN- patients (P<0.002). The proportion of 'salt-sensitive' individuals was 67% in offspring of DN+ patients vs 20% in offspring of DN- patients (P<0.05). In all groups, a high salt diet caused a comparable decrease of PRA and p-aldosterone accompanied by an increase in ANP. The urinary (THF + 5alphaTHF)/THE ratio was 1.23+/-0.36 in salt-sensitive individuals and 0.99+/-0.33 (P<0.03) in salt-resistant subjects, consistent with increased activity of 11betaHSD2. CONCLUSIONS: BP is more salt sensitive in offspring of type 2 diabetic patients with diabetic nephropathy. The salt sensitivity of BP may be an intermediate phenotype in individuals with a high risk of future diabetic nephropathy.     

Association of ALOX12 gene polymorphism with all-cause and cardiovascular mortality in diabetic nephropathy

Purpose

Cardiovascular (CV) events are the first cause of death in patients with chronic renal disease (CKD) and in patients with type 2 diabetes mellitus (DM2). The combination of CKD and DM2 elevates the risk of both cardiovascular disease (CVD) and death in this high-risk population. Besides traditional risk factors, such as dyslipidemia, smoking, obesity, and carotid atherosclerosis, novel factors are under investigation such as genetic polymorphisms. Lipoxygenases (LOXs) and their genes are of critical importance in oxidative stress, inflammation, and atherosclerosis. The aim of the study is to clarify a potential ALOX12 role in CVD presence and progress of diabetic patients in different stages of nephropathy.

Methods

We studied 145 patients with a documented history of DM2 for at least 10 years and diabetic nephropathy (DN), mean age 68 ± 9 years, body mass index 31 ± 5 kg/m², and different stages of renal disease, depending on glomerular filtration rate. The sample population consisted of two groups: 108 DM2 patients with DN in all five stages of CKD and 37 DM2 patients as controls. Anthropometric and clinical characteristics, interview for history of previous CV event, and assessment of carotid intima-media thickness (cIMT) were recorded at baseline. All patients were genotyped for ALOX12 polymorphisms with focus on rs14309. Genotypes (AA, AG, and GG) were evaluated for any possible role in CVD, and grouping was performed on A genotype, which is the dominant model. All participants were followed over a period of 7 years, and the end points studied were all-cause mortality, CV mortality, and CV events. CV events were defined as myocardial infarction (MI), stroke, or peripheral artery disease.

Results

The GG genotype has been significantly associated with cIMT levels above 0.86 mm and with history of MI. Regarding the presence of an atherosclerotic plaque in either carotid artery, no significant association was found when the genotypes were assessed on their own. After grouping, though, GG genotype revealed a significant association between carotid plaque formation and atheromatosis. Kaplan–Meier analysis revealed that ALOX12 gene GG genotype predicted all-cause mortality, CV mortality, and CV events. Similarly, when AA and AG genotypes were grouped, Kaplan–Meier analysis showed that patients with GG genotype presented an even more significant higher all-cause mortality, CV mortality, and CV events compared with AA and AG genotypes combined. After adjustment for several traditional risk factors, multivariate Cox proportional hazard analysis showed that patients with the GG genotype had a significant higher risk of all-cause mortality, a threefold increase in CV mortality, and a twofold increased risk for CV events compared to patients with the AA or the AG genotype.

Conclusion

ALOX12 rs14309 GG genotype expression was found to be significantly associated with MI, higher cIMT, increased CV events, CV, and overall mortality. This phenomenon could be partially explained by the increased platelet proaggregatory activity of AA products and the control they exert in thrombotic occurrence and plaque formation.

     

Orthostatic hypotension at the introductory phase of haemodialysis predicts all-cause mortality.

BACKGROUND: Since the predictive value of orthostatic hypotension (OH) at the introductory phase of haemodialysis (HD) is unknown, we examined the association between OH and all-cause death in patients who started HD between 1987 and 2001. METHODS: More than three consecutive blood pressure measurements before HD treatments (pre-HD BP) were made on each of 304 patients who had recently been started on HD and were in a stable condition. OH was defined as a drop in systolic BP of >20 mmHg or in diastolic BP of >10 mmHg after standing. RESULTS: Of 304 patients, 42% had OH. OH was significantly associated with pre-HD supine systolic BP; its severity was significantly associated with a past history of cerebrovascular disease and pre-HD supine systolic BP. During a mean follow-up of 4.0+/-3.0 years (range 0.1-13.2 years), 136 deaths were recorded. A multivariate Cox proportional hazards model analysis demonstrated that OH and a past history of cerebrovascular disease were independent predictors of all-cause death. The comparison by Kaplan-Meier analysis of the overall survival of patients with and without OH was significant. CONCLUSIONS: Our findings validate OH at the introductory phase of HD as a novel independent predictor of all-cause mortality among HD patients.     

Pulmonary hypertension as an independent predictor of cardiovascular mortality and events in hemodialysis patients

Background

Hemodialysis patients are at an increased risk of cardiovascular (CV) morbidity and mortality. Pulmonary hypertension (PH) has been recently reported as a new entity and unrecognized threat in maintenance hemodialysis (MHD) patients, whether PH predicts CV mortality and events in this population remains unknown. The aim of the present study was to determine the value of PH in predicting CV mortality and events in a prospective cohort of MHD patients.

Methods

We studied 278 MHD patients (98 with and 180 without PH) in Guangdong General Hospital Blood Purification Center, Guangzhou, China. All patients had been followed up for 2 years, and in survival analysis, we considered time to death or first cardiovascular event. The endpoints were all-cause mortality, CV mortality and CV events. PH was defined as systolic pulmonary artery pressure (SPAP) ≥ 35 mmHg as determined by Doppler echocardiographic evaluation.

Results

Of the 278 MHD patients, 53 (19.1 %) died as a result of all causes, 28 (10.1 %) died from CV events (52.8 % of causes of death), and 87 (31.3 %) had new-onset CV events. The survival curve showed that all-cause and CV mortality and new-onset CV events were higher in PH group than the non-PH group. In a multivariate Cox proportional hazard model, the adjusted HR for all-cause mortality, CV mortality and CV events was 1.85 [95 % confidence interval (CI) 1.03–3.34], 2.36 (95 % CI 1.05–5.31) and 2.27 (95 % CI 1.44–3.58), respectively.

Conclusions

Our study showed that PH was an independent predictor of all-cause mortality and CV mortality and events in MHD patients. We suggest to evaluate SPAP in MHD patients in order to stratify risk of death and CV events.     

Prehypertension - time to act

The term "prehypertension" defined as systolic blood pressure between 120 and 139 mmHg and/or diastolic pressures between 80 and 89 mmHg has now gained general acceptance. Prehypertension is associated with ~3-fold greater likelihood of developing hypertension, and roughly twice the number of cardiovascular events, than BP < 120/80 mmHg. When compared with normotensive individuals, prehypertensive individuals are more likely to be overweight and obese, to have other cardiovascular risk factors, to progress to established hypertension, and to experience premature clinical cardiovascular disease. The major unresolved issue is the appropriate management of such patients. Lifestyle modification is recommended for all patients with prehypertension as it effectively reduces rate of cardiovascular events. Presently pharmacological therapy is indicated for some patients with prehypertension who have specific comorbidities, including diabetes mellitus, chronic kidney disease, and coronary artery disease.     

Albuminuria is a target for renoprotective therapy independent from blood pressure in patients with type 2 diabetic nephropathy: post hoc analysis from the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) trial

Albuminuria reduction could be renoprotective in hypertensive patients with diabetic nephropathy. However, the current use of renin-angiotensin-system intervention is targeted to BP only. Therefore, this study investigated the adequacy of this approach in 1428 patients with hypertension and diabetic nephropathy from the placebo-controlled Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study. Investigated were the extent of discordance in treatment effects on systolic BP (SBP) and albuminuria and its association with renal outcome in a multivariate Cox model. Among patients with a reduced SBP during treatment, a lack of albuminuria reduction was observed in 37, 26, and 51% (total, losartan, and placebo, respectively) at month 6. SBP or albuminuria reduction was associated with a lower risk for ESRD, whereas combined SBP and albuminuria reduction was associated with the lowest risk for events. Across all categories of SBP change, a progressively lower ESRD hazard ratio was observed with a larger albuminuria reduction. A lower residual level of albuminuria was also associated with lower ESRD risk. In conclusion, changes in albuminuria are not concordant in a substantial proportion of patients when titrated for BP. Meanwhile, the ESRD risk showed a clear dependence on albuminuria reduction. The ESRD risk also showed dependence on the residual level of albuminuria, even in patients who reached the current SBP target. Antihypertensive treatment that is aimed at improving renal outcomes in patients with diabetic nephropathy may therefore require a dual strategy, targeting both SBP and albuminuria reduction.     

Impact of systolic pulmonary artery pressure on all-cause mortality in elderly cardiac patients

Objective. Elevated systolic pulmonary artery pressure (sPAP) is common among elderly patients with cardiac and pulmonary diseases. The lowest level of sPAP associated with increased mortality rate in octogenarians with cardiac diseases is however not sufficiently studied. Therefore, the present study aimed to identify the lowest level of sPAP associated with increased 5-year all-cause mortality in this patient group. Design. Of 538 octogenarians presented at the three Sahlgrenska University Hospitals (Sahlgrenska, Östra and Mölndal) with either congestive heart failure (CHF) or acute coronary syndrome (ACS), only 302 patients who had undergone echocardiography with data on sPAP were included in the present study. In order to identify the lowest level of sPAP associated with increased mortality rate, Cox proportional-hazard regression multivariable models were built for sPAP levels as low as 30?mmHg and upward with 5?mmHg intervals. Results. sPAP?>35?mmHg was identified as the lowest level associated with increased 5-year all-cause mortality (HR?=?1.7, 95% of CI?=?1.1–2.6 and p?=?.013). Every increase of 5?mmHg in sPAP was associated with a 10% increased relative risk for all-cause mortality. Conclusions. In octogenarians with cardiac diseases the lowest level of sPAP associated with increased all-cause mortality was >35?mmHg and the mortality rate increased with increasing sPAP.     

The relationship between survival rate and intradialytic blood pressure changes in maintenance hemodialysis patients

Objective: The objective of this study is to investigate the relationship between blood pressure changes and all-cause mortality, and between blood pressure changes and cardiovascular mortality, for maintenance hemodialysis (MHD) patients during dialysis.

Methods: Data regarding general condition, biochemical indices, and survival prognosis of MHD patients who were treated at the Shanghai Jiao Tong University School of Medicine-affiliated Renji Hospital from July 2007 to December 2012 were collected, in order to evaluate the relationship between patients’ blood pressure changes during hemodialysis and mortality.

Results: Among 364 patients, with an average age of 63.07?±?13.93?years, an average dialysis vintage of 76.00 (range, 42.25–134.00) months, and a follow-up time of 54.86?±?19.84?months, there were 85 cases (23.4%) of all-cause death and 46 cases (14.2%) of cardiovascular death. All-cause mortality and cardiovascular mortality were lowest (OR, 0.324 and 0.335; 95% CI, 0.152–0.692 and 0.123–0.911; p value, .004 and .032, respectively) in patients whose systolic blood pressure difference (ΔSBP) before and after dialysis was between 7.09 and 14.25?mmHg. Kaplan–Meier analysis indicated that both all-cause mortality and cardiovascular mortality were markedly increased for patients with ΔSBPless than ?0.25?mmHg (p value, .001 and .044, respectively). Cox regression analysis showed that ΔSBPKt/v and albumin were independent risk factors for all-cause mortality in MHD patients.

Conclusions: MHD patients whose blood pressure increased significantly after hemodialysis had a higher risk of dying; ΔSBP, hemoglobin concentration, Kt/v and albumin were independent risk factors for all-cause mortality in MHD patients.     

Association of low blood pressure with increased mortality in patients with moderate to severe chronic kidney disease.

BACKGROUND: Blood pressure shows an inverse association with mortality in patients with chronic kidney disease (CKD) on dialysis. It is unclear if the same phenomenon exists in patients with CKD not yet on dialysis. METHODS: We examined the association of systolic (SBP) and diastolic (DBP) blood pressure with all-cause mortality in a historical prospective cohort of 860 patients (age 68.1+/-10.1 years, 99.1% male, 24.4% black) with estimated glomerular filtration rate (GFR) < 60 ml/min/1.73 m2. We used Cox models to adjust for the effects of age, race, diabetes mellitus, atherosclerotic cardiovascular disease (ASCVD), congestive heart failure, smoking, antihypertensive medications, body mass index, GFR, albumin, cholesterol, haemoglobin and proteinuria. To examine the role of comorbidities, we performed subgroup analyses based on prevalent ASCVD status and level of estimated GFR. RESULTS: Higher SBP and higher DBP were both associated with lower mortality [adjusted hazard ratio (95% confidence interval) for SBP 133-154, 155-170 and > 170 mmHg, compared with < 133 mmHg, respectively: 0.61 (0.44-0.85), 0.62 (0.45-0.87) and 0.68 (0.49-0.96); and for DBP 65-75, 76-86 and > 86 mmHg, compared with < 65 mmHg: 0.85 (0.62-1.18), 0.72 (0.52-1.00) and 0.60 (0.41-0.86)]. The same association was present for both SBP and DBP only in subgroups with GFR < or = 30 ml/min/1.73 m2 and for DBP only in the subgroup with ASCVD. CONCLUSIONS: Lower blood pressure is associated with higher mortality in patients with moderate to severe CKD, but interactions with kidney function and with ASCVD suggest that blood pressure may play a surrogate rather than a causative role in this association.     

Predictors of cardiovascular events in patients with type 2 diabetic nephropathy and hypertension: a case for albuminuria

Individuals with type 2 diabetes and nephropathy represent a particularly high-risk group for both adverse cardiac as well as renal events. Using the Irbesartan in Diabetic Nephropathy Trial (IDNT) cohort, our objective was to determine baseline characteristics of individuals with type 2 diabetic nephropathy and hypertension predictive for cardiac events. IDNT identified 1715 individuals with type 2 diabetic nephropathy and hypertension having serum creatinine of 1.0 to 3.0 mg/dL and urinary albumin excretion rates > or = 900 mg/day. A cardiovascular (CV) composite was used consisting of CV death, nonfatal MI, hospitalization for heart failure, stroke, amputation, and coronary and peripheral revascularization. Using multivariable Cox regression analysis, 41 baseline characteristics determined a priori were analyzed for their potential relationship to risk of experiencing a CV event. Of the 1715 individuals, 518 (30.2%) had at least one of the CV composite end points. Older age, male gender, longer duration of diabetes, history of cardiovascular disease, history of CHF, high urinary albumin:creatinine ratio, and low serum albumin were strong predictors for CV events; of these, prior history of CVD (RR 2.00, 95% CI 1.63-2.45; P < 0.0001) and high urinary albumin:creatinine ratio (RR 1.29 per natural log unit, 95% CI 1.13-1.48; P = 0.0002) at baseline were highly predictive for cardiovascular events. In conclusion, among individuals with hypertension and diabetic nephropathy, both the degree of albuminuria and lower serum albumin levels provide additional prognostic information concerning cardiovascular risk, in addition to traditional coronary risk factors.