Angiotensin receptor blockade and arterial compliance in chronic kidney disease: a pilot study.

BACKGROUND: Almost 20 million people in the US have chronic kidney disease (CKD). Cardiovascular disease and arterial wall abnormalities are common in this population. Because angiotensin II may have adverse effects on the arterial wall, we hypothesized that an angiotensin receptor blocker (ARB) would improve arterial compliance as compared with placebo in subjects with CKD. METHODS: We performed a double-blinded, placebo-controlled pilot study in which 25 subjects with stages 2 or 3 CKD and proteinuria <1 g were randomized to either the ARB, eprosartan, or placebo and titrated to achieve a goal blood pressure (BP) <130/85 mm Hg. Arterial compliance was measured at baseline and at 8 weeks. RESULTS: Baseline characteristics were similar between the groups and included mean estimated glomerular filtration rate 63 +/- 14 ml/min/1.73 m(2), heart rate 76 +/- 10 beats/min, BP 142 +/- 12/81 +/- 8 mm Hg, 64% diabetic, 44% male, and 40% white, though subjects in the eprosartan group were younger (60 +/- 12 vs. 70 +/- 6 years, p = 0.01). There were no significant differences between the groups in large or small artery compliance measurements either at baseline or at 8 weeks, but there was a statistically significant improvement from baseline in small artery compliance in the eprosartan group (from median 2.5 ml/mm Hg x 100 [90% CI (1.1, 4.7)] to 4.0 ml/mm Hg x 100 [90% CI (1.9, 6.7)] (p = 0.01)) not seen in the placebo group. CONCLUSION: Use of an ARB to achieve recommended BP is associated with improved small artery compliance in people with CKD, though larger studies are needed to confirm these findings.

Is proteinuria a plausible target of therapy?

Microalbuminuria is an independent marker of cardiovascular risk, irrespective of kidney disease. Recent pharmacologic interventions have resulted in a significant delay and even an arrest in the progression of microalbuminuria to macroalbuminuria or to chronic kidney disease. Focus should be placed on agents that not only lower blood pressure but also improve albuminuria levels. Current guidelines recommend that hypertensive patients with renal disease should be started on agents that block the renin-angiotensin-aldosterone system, such as angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). The use of three to four different agents is frequently necessary to reach the guideline goal blood pressure of 130/80 mm Hg.

Diabetes and chronic kidney disease: tragedy and challenge.

Management of hypertension in diabetic nephropathy is challenging and generally requires a minimum of three different and complementary antihypertensive agents to achieve the recently recommended blood pressure (BP) goal of <130/80 mm Hg in order to reduce cardiovascular (CV) risk and preserve kidney function. Commonly used antihypertensive combinations include an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker, agents that have compelling indications for use in diabetic renal disease, added to a diuretic, generally a thiazide-type agent. If additional therapy is required, either a beta-blocker or calcium antagonist may be added. Beta-blockers are particularly effective in people with a high sympathetic drive, i.e. high pulse rates, to lower BP and reduce CV risk while reducing proteinuria and slowing decline of kidney function. In light of this information, it is disturbing that a recent analysis of the NHANES III database indicates that only about 11% of people with diabetic kidney disease have achieved the target BP of <130/80 mm Hg. Recent data from Denmark demonstrate that focusing on total CV risk reduction among people with diabetes, including achievement of recommended BP and lipid goals along with the use of aspirin, exercise and a proper diet, can reduce the absolute risk of a CV event by 20% over less intensive treatment.

Clinical and angiographic outcomes of cardiac transplant patients treated with intracoronary beta-radiation for in-stent restenosis: a case series.

BACKGROUND: Vascular brachytherapy (VBT) is effective for the treatment of in-stent restenosis (ISR), however, the effect of VBT clinical and angiographic outcomes of patients with ISR who have undergone orthotopic heart transplantation (OHT) requires further study. METHODS: All OHT patients with ISR treated with VBT using the Novoste Beta-Cath System at Rush University Medical Center were identified, and the clinical and angiographic outcomes were evaluated. RESULTS: Four OHT patients with ISR who underwent VBT were identified. The mean age was 48.5 years, and the mean duration posttransplantation was 7.5 years. The mean reference coronary vessel diameter was 3.06 mm. The primary interventional device utilized prior to VBT was cutting balloon angioplasty (CBA) in 75% and percutaneous balloon angioplasty in 25%. The mean duration of follow-up after VBT was 11 months. There were no deaths attributable due to cardiac disease, no myocardial infarction, and no target vessel revascularization on follow-up. Overall survival during this period was 75%, with one mortality due to stroke 8 months after VBT. CONCLUSIONS: VBT for the treatment of ISR in patients who have undergone OHT appears safe and feasible and is associated with acceptable clinical and angiographic outcomes.

Predictors of late cardiac events following treatment with Sr-90 beta-irradiation for instent restenosis.

BACKGROUND: Intracoronary radiation therapy (IRT) with Sr-90 using the Novoste Beta-Cath system has been shown to be an effective therapy for instent restenosis (ISR), but the temporal occurrence of cardiac events and the predictors of late complications require further investigation. METHODS: We analyzed the demographics, lesion characteristics and clinical outcomes of 138 consecutive patients with ISR treated with IRT from September 1998 to March 2002. Major adverse cardiac events (MACE) were defined as death, myocardial infarction (MI) or target vessel revascularization (TVR). Characteristics of early (< or =8 months) and late (>8 months) failures were analyzed. RESULTS: Thirty-two (23.1%) of 138 patients had MACE on follow-up; 25% (8/32) of failures occurred late after treatment with IRT. A comparison of the clinical and angiographic profile of early and late failures using univariate analysis indicates no correlations to late failure following IRT. Duration to failure after IRT was 14.25+/-3.69 months in the late group compared to 4.63+/-2.86 months in the early group (P<.001). CONCLUSIONS: Late MACE after IRT with Sr-90 for ISR occur beyond the traditional period for clinical restenosis in 25% of cases and are difficult to predict. Further study is warranted to identify patients at risk for the development of late complications after IRT.

Visual assessment of procedural results following treatment with Sr-90 beta-radiation for instent restenosis.

BACKGROUND: Visual assessment (VA) of postprocedural % diameter stenosis (DS) is used routinely in clinical practice to determine the adequacy of coronary intervention. Although VA has been shown to underestimate final %DS after balloon angioplasty compared to quantitative coronary angiography (QCA), the impact of this effect on clinical outcomes following treatment with intracoronary radiation therapy (IRT) with Sr-90 for instent restenosis (ISR) is unknown. METHODS: To determine the effect of VA on the rate of major adverse cardiac events (MACEs) after IRT for ISR, we compared the clinical outcomes of 102 consecutive patients based on postprocedural %DS by QCA vs. %DS by VA. MACE was defined as death, M1 or need for target vessel revascularization (TVR). RESULTS: MACE rates for the 102 consecutive patients grouped according to postprocedural %DS by QCA and VA were compared. The mean %DS by QCA was 30.7%, while the mean %DS by VA was 12.5%. The mean %DS by VA across the QCA subgroups were 13.67%, 10.71% and 13.37%, respectively (P = .244). Fifty-two patients (51.0%) had %DS > 30% by QCA with the highest MACE percentage occurring in this subgroup. CONCLUSION: VA underestimated the %DS compared to QCA, and it was associated with worse MACE following treatment with Sr-90 for ISR.