Cardiovascular risk assessments in peripheral arterial disease : results of a ten-year follow-up of a Swedish population-based cohort

Abstract: Background An updated knowledge on natural history in Peripheral Arterial Disease (PAD) is lacking, in particular for the asymptomatic stage (APAD). The disease has strong associations with other atherosclerotic manifestations such as myocardial infarction or stroke, which could be prevented with prophylactic measures. PAD is easily detected through simple ankle and brachial blood pressure measurements, why screening for this condition has been suggested but is yet not proven cost-effective. Identification of PAD could be useful in cardiovascular (CV) risk assessments. To improve health in society and to reduce costs for care, improved prophylactic strategies is needed in CV management. Before that, improved knowledge of the natural history of PAD is essential. This project describes mortality, CV outcome and treatment patterns in symptomatic and asymptomatic PAD men and women. Methods and Results Study I A population sample of 5080 subjects, selected through randomization, was enrolled in the study in 2004-2005. Participants completed health state questionnaires and underwent ankle brachial index (ABI) measurements for classification into PAD severity stages. A follow-up was conducted by the end of 2015 using data from Swedish governmental national registers for cause of death, which was compared with the PAD stage determined at baseline in 2005. The age-adjusted hazard ratios for a main cause of death by a CV event were 1.9 [95% CI 1.5-2.3] in Asymptomatic PAD, 2.6 [95% CI 2.1-3.4] in Intermittent Claudication, and 3.5 [95% CI 2.3-5.2] in Severe Limb Ischemia stage groups. Study II This was a prospective observational population-based cohort study based on physical examinations and questionnaires at baseline supplemented with national register data between 2005 and 2015. Subjects were placed in subgroups defined by ABI levels and reported symptoms as in study I. After adjustments for age, comorbidity, and sex, the risk was almost doubled for CV death in Intermittent Claudication and APAD subjects (HR 1.95 and 1.80) as compared to a reference population. The risk for other comorbidity as diabetes, non-fatal myocardial infarction and stoke and renal failure was doubled in PAD. Some 60% of symptomatic PAD subjects received the pharmacological prophylactic treatment as recommended in guidelines. Study III This study evaluated the risks for adverse CV events in subjects with APAD in combination with different known traditional CV risk factors over a ten-year observation period. For subjects with hypertension at baseline the CV mortality incidence was 35.4 deaths per 1000 person-years when combined with APAD and 11.7 without. In women with hypertension but without other risk factors, presence of APAD increased the age-adjusted Hazard Ratio (HR) for fatal and non-fatal CV events by 1.86 [CI 1.54,2.24, p<0.001]. Study IV This prospective study assessed the differences in CV outcome if using the highest (ABI-HI) or lowest (ABI-LO) ankle blood pressure for ABI calculation for PAD diagnosis in a population-based cohort. The prevalence of PAD, defined by an ABI<0.9, by using ABI-LO and ABI-HI was 16.3% (n=799) and 9.6 % (n=469), respectively. For the subgroups defined by ABI-LO and ABI-HI, the age-adjusted HR [95% CI] for the composite outcome CV mortality and non-fatal CV events, was 1.25 [1.06-1.49] and 2.11 [1.85-2.39] respectively. The predictive value of an ABI<0.9 to foresee a future event was low for both calculation methods. Conclusions The mortality is more than doubled in symptomatic PAD patients compared with reference subjects and increase by severity of PAD stage. The prognosis for this group has not changed over the last decades in contrary to other CV manifestations. Among all PAD subjects, CV causes were the most common main cause of death (45%) and a CV event was present as either the main or one of the three most common contributing causes of death in 64% of the cases. APAD subjects confer almost similar risk for CV events as symptomatic patients. PAD is more common in women, but men face a higher risk for death and CV events. Some 60% of symptomatic PAD subjects received prophylactic drugs according to guidelines by 2015. Subjects with APAD and any other CV risk factor have significantly higher risks for CV events and could therefore constitute suitable populations for further studies of screening with ABI measurements and subsequent intensified CV prophylactic treatment. When using the ABI-LO method more subjects at risk were identified, but their average risk was lower when comparing to the ABI-HI method which identified less subjects at risk. These differences are important to be aware of in further studies of screening. ABI measurements should be considered an important indication in aggressive multifactorial risk factor reduction in populations with any other prevalent CV risk factor.