The association of the ankle-brachial index with incident coronary heart disease: the Atherosclerosis Risk In Communities (ARIC) study, 1987-2001

Abstract Background Peripheral arterial disease (PAD), defined by a low ankle-brachial index (ABI), is associated with an increased risk of cardiovascular events, but the risk of coronary heart disease (CHD) over the range of the ABI is not well characterized, nor described for African Americans. Methods The ABI was measured in 12186 white and African American men and women in the Atherosclerosis Risk in Communities Study in 1987–89. Fatal and non-fatal CHD events were ascertained through annual telephone contacts, surveys of hospital discharge lists and death certificate data, and clinical examinations, including electrocardiograms, every 3 years. Participants were followed for a median of 13.1 years. Age- and field-center-adjusted hazard ratios (HRs) were estimated using Cox regression models. Results Over a median 13.1 years follow-up, 964 fatal or non-fatal CHD events accrued. In whites, the age- and field-center-adjusted CHD hazard ratio (HR, 95% CI) for PAD (ABI 1.0, in all race-gender subgroups. The association between the ABI and CHD relative risk was similar for men and women in both race groups. A 0.10 lower ABI increased the CHD hazard by 25% (95% CI 17–34%) in white men, by 20% (8–33%) in white women, by 34% (19–50%) in African American men, and by 32% (17–50%) in African American women. Conclusion African American members of the ARIC cohort had higher prevalences of PAD and greater risk of CHD associated with ABI-defined PAD than did white participants. Unlike in other cohorts, in ARIC the CHD risk failed to increase at high (>1.3) ABI values. We conclude that at this time high ABI values should not be routinely considered a marker for increased CVD risk in the general population. Further research is needed on the value of the ABI at specific cutpoints for risk stratification in the context of traditional risk factors

Vasodilators in the treatment of acute heart failure: what we know, what we don’t

Although we have recently witnessed substantial progress in management and outcome of patients with chronic heart failure, acute heart failure (AHF) management and outcome have not changed over almost a generation. Vasodilators are one of the cornerstones of AHF management; however, to a large extent, none of those currently used has been examined by large, placebo-controlled, non-hemodynamic monitored, prospective randomized studies powered to assess the effects on outcomes, in addition to symptoms. In this article, we will discuss the role of vasodilators in AHF trying to point out which are the potentially best indications to their administration and which are the pitfalls which may be associated with their use. Unfortunately, most of this discussion is only partially evidence based due to lack of appropriate clinical trials. In general, we believe that vasodilators should be administered early to AHF patients with normal or high blood pressure (BP) at presentation. They should not be administered to patients with low BP since they may cause hypotension and hypoperfusion of vital organs, leading to renal and/or myocardial damage which may further worsen patients’ outcome. It is not clear whether vasodilators have a role in either patients with borderline BP at presentation (i.e., low-normal) or beyond the first 1–2 days from presentation. Given the limitations of the currently available clinical trial data, we cannot recommend any specific agent as first line therapy, although nitrates in different formulations are still the most widely used in clinical practice

Kidney function and risk of peripheral arterial disease: results from the Atherosclerosis Risk in Communities (ARIC

Chronic kidney disease (CKD) is associated with an increased risk for cardiovascular disease, but its association with peripheral arterial disease (PAD) is unclear. With the use of data from the Atherosclerosis Risk in Communities (ARIC) Study, 14,280 middle-aged adults were categorized on the basis of estimated GFR >90, 60 to 89, and 15 to 59 ml/min per 1.73 m 2 for normal kidney function, mildly decreased kidney function, and stages 3 to 4 CKD, respectively. Incident PAD was defined as a new onset of ankle-brachial index <0.9 assessed at regular examinations, new intermittent claudication assessed by annual surveillance, or PAD-related hospital discharges. Incidence rates and relative risks (RR) for PAD were compared across these categories. During a mean follow-up time of 13.1 yr (186,616 person-years), 1016 participants developed PAD. The incidence rates per 1000 person-years were 4.7, 4.9, and 8.6 for the normal kidney function, mildly decreased kidney function, and CKD groups, respectively. Compared with participants with normal kidney function, the age-, gender-, race-, and ARIC field center-adjusted RR for PAD was 1.04 (95% confidence interval [CI] 0.91 to 1.18) for those with mildly decreased kidney function and 1.82 (95% CI 1.34 to 2.47) for those with CKD. After additional adjustment for cardiovascular disease risk factors, an increase in risk for incident PAD still was observed in participants with CKD, with a multivariable adjusted RR of 1.56 (95% CI 1.13 to 2.14). Patients with CKD are at increased risk for incident PAD. Development of strategies for screening and prevention of PAD in this high-risk population seems warranted

Effects of the adenosine A1 receptor antagonist rolofylline on renal function in patients with acute heart failure and renal dysfunction: results from PROTECT (Placebo-Controlled Randomized Study of the Selective A1 Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized With Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function)

Objectives: This study sought to assess the effects of rolofylline on renal function in patients with acute heart failure (AHF) and renal dysfunction randomized in PROTECT (Placebo-Controlled Randomized Study of the Selective A1 Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized With Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function). Background: Small studies have indicated that adenosine A1 receptor antagonists enhance diuresis and may improve renal function in patients with chronic heart failure or AHF. Methods A total of 2,033 patients with AHF, volume overload, estimated creatinine clearance between 20 and 80 ml/min, and elevated natriuretic peptide levels were randomized (2:1) within 24 h of hospital presentation to rolofylline 30 mg/day or intravenous placebo for up to 3 days. Creatinine was measured daily until discharge or day 7 and on day 14. Persistent worsening renal function was defined as an increase in serum creatinine ≥0.3 mg/dl at both days 7 and 14, or initiation of hemofiltration or dialysis or death by day 7. Results: At baseline, mean ± SD estimated creatinine clearance was 51.0 ± 20.5 ml/min in the placebo group and 50.4 ± 20.0 ml/min in the rolofylline group. Changes in creatinine and estimated creatinine clearance were similar between placebo- and rolofylline-treated patients during hospitalization and at day 14. After 4 days, mean body weight was reduced by 2.6 and 3.0 kg in placebo and rolofylline patients, respectively (p = 0.005). Persistent worsening renal function occurred in 13.7% of the placebo group and 15.0% of the rolofylline group (odds ratio vs. placebo: 1.11 [95% confidence interval: 0.85 to 1.46]; p = 0.44). Conclusions: In this large, phase III clinical trial, the adenosine A1 receptor antagonist rolofylline did not prevent persistent worsening renal function in AHF patients with volume overload and renal dysfunction. (A Study of the Selective A1 Adenosine Receptor Antagonist KW-3902 for Patients Hospitalized With Acute HF and Volume Overload to Assess Treatment Effect on Congestion and Renal Function [PROTECT-1], NCT00328692; and [PROTECT-2], NCT00354458