Background:

Ankle-brachial blood pressure index (ABI) is known to be a predictor for cardiovascular and total mortality. In patients with a previous myocardial infarction or stroke and in patients referred for coronary angiography, the occurrence of peripheral arterial disease (PAD) has been shown to increase the risk further. In epidemiological studies, ankle blood pressure was measured in the foot arteries by ultrasound Doppler. However, this technique is not readily available in most general practices, so it is important to evaluate whether simpler measurement of the ABI using routine blood pressure measurement in the arm and palpation of the foot pulse is of predictive value.

Aim:

• To assess the prognostic importance of PAD as evaluated by a simpler measurement of ankle blood pressure index (ABI), and
• To evaluate the effect of ramipril on the prevention of major cardiovascular events in PAD patients.

Patient characteristics:

8986 patients (³ 55 years of age) with a history of

• Coronary artery disease, or

• Stroke, or

• Peripheral vascular disease (either intermittent claudication with an ABI < 0.9, or previous vascular intervention or limb amputation for PAD), or

• Diabetes plus one other cardiovascular risk factor (hypertension, elevated total cholesterol level, low high density lipoprotein cholesterol level, cigarette smoking, or microalbuminuria).

Exclusion criteria:

Patients with a history of

• heart failure, or

• low left ventricular ejection fraction < 0.40, or

• on ACE inhibitor treatment, or

• uncontrolled hypertension or

• overt nephropathy, or

• myocardial infarction or stroke within 4 weeks before entering the study.

Treatment groups:

Ramipril 10 mg daily vs. Placebo

Study duration:

4.5 years

Study outcomes:

Primary outcome
A composite of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke.

Secondary outcomes
The individual components of the composite end-point, all-cause death, hospitalizations for heart failure and diabetic complications.

Results:

• Ramipril reduced the risk of cardiovascular events in patients with clinical PAD as well as with subclinical PAD, regardless of ABI.

• No heterogeneity was seen in treatment effects across the various subcategories of individuals with different levels of ABI on any of the outcomes examined indicating the value of ramipril in patients across a range of risk levels.

• Clinical PAD and a low ABI at baseline in the absence of clinical PAD were strong predictors for cardiovascular morbidity and mortality. This was so for the primary endpoint and for each individual component of the primary endpoint.

• ABI also predicted all-cause mortality.

  ABI categories	Mortality
  Normal ABI (>0.9) & no clinical PAD	8.5%
  Moderately pathologic ABI (0.9-0.6)	12.4%
  Severely pathologic ABI (<0.6)	14.2%
  Clinical PAD	17.5%

  
  
• Low ABI also predicted the development of heart failure and diabetic complications. Clinically symptomatic PAD also predicted future vascular procedures (mainly CABG).

Conclusions:

• Ramipril reduced the risk of clinical outcomes in those with a clinical history of PAD as well as in the patients with subclinical PAD.

• The ABI even if measured with simple palpation of the foot arteries is a strong and independent predictor for future cardiovascular morbidity and mortality, as well as for all-cause mortality.

European Heart Journal 2004; 25: 17-24