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Prevalence of peripheral artery disease in the elderly population in urban and rural areas of Central Africa: the EPIDEMCA studyEuropean Journal of Preventive Cardiology, 22
Abstract Importance Peripheral arterial disease (PAD) causes significant morbidity and is an important risk factor for cardiovascular disease–related mortality. However, the burden of PAD in sub-Saharan Africa is poorly understood. Objective To assess epidemiological and clinical reports regarding PAD from sub-Saharan Africa such that the regional epidemiology and management of PAD could be described and recommendations offered. Evidence Review A systematic search in PubMed, Medline, Embase, the Cumulative Index to Nursing and Allied Health Literature, and Google Scholar for reports pertaining to the epidemiology and/or management of PAD in sub-Saharan Africa was performed. Reports that met inclusion criteria were sorted into 3 categories: population epidemiology, clinical epidemiology, and surgical case series. Findings were extracted and described. Findings The search returned 724 records; of these, 16 reports met inclusion criteria. Peripheral arterial disease epidemiology and/or management was reported from 10 of the 48 sub-Saharan African countries. Peripheral arterial disease prevalence ranged from 3.1% to 24% of adults aged 50 years and older and 39% to 52% of individuals with known risk factors (eg, diabetes). Medical management was only described by 2 reports; both documented significant undertreatment of PAD as a cardiovascular disease risk factor. Five surgical case series reported that trauma and diabetes-related complications were the most common indications for vascular surgery. Conclusions and Relevance The prevalence of PAD in sub-Saharan Africa may be equal to or higher than that in high-income countries, exceeding 50% in some high-risk populations. In addition to population-based studies that better define the PAD burden in sub-Saharan Africa, health systems should consider studies and action regarding risk factor mitigation, targeted screening, medical management of PAD, and defining essential vascular care. Introduction The epidemiological transition from predominately infectious to noncommunicable diseases in sub-Saharan Africa has made cardiovascular disease (CVD) a public health priority.1-3 Cardiovascular disease will be the leading cause of death in low- and middle-income countries (LMICs), including those in sub-Saharan Africa, as early as 2030.4 This increase is attributed to both longer life expectancy and greater exposure to chronic disease risk factors (eg, sedentary lifestyle, poor dietary habits, and smoking).4-6 In addition to ischemic heart and cerebrovascular disease, peripheral arterial disease (PAD) is responsible for an under-recognized and significant burden of death and disability in LMICs.7,8 Peripheral arterial disease is a coronary artery disease risk equivalent and is often the presenting condition of both CVD and diabetes in sub-Saharan Africa.9 Furthermore, there is evidence that the burden of PAD is rising more rapidly than other forms of CVD in sub-Saharan Africa.5,10 Therefore, in addition to building an evidence base regarding PAD in sub-Saharan Africa, defining the regional PAD burden may improve the understanding of CVD in these countries more broadly and lead to effective interventions. A meta-analysis of global PAD prevalence in LMICs and high-income countries (HICs)6 estimated that 14.2 million people had PAD in sub-Saharan Africa in 2010. However, this estimate was generated based on 12 studies from LMICs worldwide and sub-Saharan Africa risk factor prevalence, rather than country- or region-specific disease prevalence. Published estimates of PAD prevalence in sub-Saharan Africa vary more than 10-fold (1.7%-53%) based on study population, study design, and how PAD was defined and diagnosed.11 These widely variable estimates demand a closer evaluation of the evidence regarding PAD prevalence in sub-Saharan Africa. To better characterize the health burden of PAD in sub-Saharan Africa, we performed a scoping review of the literature to describe PAD epidemiology and management in the region. In doing so, we hoped to clarify what is currently known, inform discussion of guidelines and possible interventions, and identify future research priorities.12 Box Section Ref ID Key Points Question What is the prevalence and management of peripheral arterial disease (PAD) in sub-Saharan Africa? Findings In this scoping review, prevalence of PAD was highly variable with as few as 3% or as many as 52% of individuals in sub-Saharan Africa having PAD, depending on the geographic region and risk factors of the individuals. Medical management was described in only 2 studies, both of which reported significant undertreatment of PAD. Meaning The prevalence of PAD in sub-Saharan Africa may be equal to or higher than that in high-income countries. Health systems should consider studies and action regarding risk factor mitigation, targeted screening, and medical management. Methods Scoping Review A preliminary search using database-specific language to identify reports of PAD from sub-Saharan Africa returned no high-level evidence. Thus, our ability to conduct a formal systematic review with a narrowly focused research question and report exclusion based on study design and bias was limited. Instead, we performed a scoping review, which consists of a systematic literature search with broader record inclusion criteria and a structured qualitative analysis of retrieved reports.13 Search Strategy A systematic search strategy was designed to identify all records that described the epidemiology and/or the clinical management of lower extremity PAD in adults (≥18 years) living in sub-Saharan Africa. Surgical management was incorporated into the review because PAD is often a surgically managed disease in HICs and the capacity for vascular surgical care in sub-Saharan Africa is poorly characterized.14-16 The search strategy included terms for geography, dates, and a sensitive combination of keyword and structured index terms (see eMethods in the Supplement for complete search strategy). The search was conducted in 5 databases: PubMed, Medline, Embase, the Cumulative Index to Nursing and Allied Health Literature, and Google Scholar. Eligibility Studies were eligible for inclusion if they reported prevalence or management of PAD in at least 1 sub-Saharan African country or a subpopulation therein. Records from January 1, 2000, to April 1, 2015, were included to describe the epidemiology of PAD and its management. Given the few reports on PAD in sub-Saharan Africa, we did not exclude studies based on risk of bias or study design. Records without full-text availability were excluded. All languages were included. The primary outcomes of interest were prevalence of PAD as defined by the report and any description of the medical or surgical management of PAD. The PRISMA guidelines for study design and reporting were used where applicable.17 Record and Report Management Records were screened for relevance to inclusion criteria and duplication of data from previously published reports. The references of each included report were reviewed for relevant citations. Reports were then separated into population-based studies, clinical cohorts, and surgical case series. The latter 2 categories were described separately, given the significant differences of these estimates in settings with limited access to care.18,19 In addition, odds ratios for several risk factors traditionally related to PAD were extracted. Data Analysis Odds ratios for PAD risk factors in sub-Saharan Africa were not pooled owing to heterogeneity between the studies and risk factor definitions that were ambiguous or not directly comparable (eg, tobacco use and active smoker). Therefore, we only reported the odds ratios along with a reference value from Fowkes et al6 in the form of a forest plot. To our knowledge, the reference value provides the best estimate of the effect of these risk factors on PAD in LMICs based on a large meta-analysis. Results Our search returned 724 records. Two additional records were included based on bibliographic review, yielding a total of 726 records (Figure 1). Titles and abstracts were screened for relevance; 627 records were subsequently excluded (86% of retrieved records). Of the remaining 99 records, 77 were excluded after abstract review (11% of retrieved records); 5 did not have full text records; and 1 was a duplicate. The remaining 16 reports (2.2% of retrieved records) were reviewed in full. Nine reports collected primary data on the prevalence of PAD in sub-Saharan Africa, and 5 reports were surgical case series. These reports are summarized in the Table. Five reports provided odds ratios for specific risk factors.20-24 These are discussed in the context of the studies below, and presented in Figure 2 and the eTable in the Supplement. Community-Based Surveys Five reports were cross-sectional community-based surveys. Community-based surveys do not rely on patients who seek and/or have access to medical and/or surgical care. Therefore, these reports provided the most accurate and generalizable estimates of PAD in sub-Saharan Africa.19,25 Two studies were conducted in the neighboring countries of the Central African Republic and the Republic of the Congo.21,26 Beginning in 2008, Guerchet et al22,26 performed cross-sectional, community-based surveys in districts of Bangui, Central African Republic, and Brazzaville, the Republic of the Congo. They exhaustively sampled adults older than 65 years of age in a single district. In total, 976 individuals were surveyed: 515 in Brazzaville and 461 in Bangui. The combined prevalence of PAD was 24%. However, prevalence differed significantly by community: 15% in Bangui and 32% in Brazzaville.26 Desormais et al21 performed a similar study in the same countries in 2011 to 2012. However, they included 1 rural area per country. The study measured ankle brachial indexes (ABIs) on 1871 participants aged 65 years or older (939 in Central African Republic; 932 in the Republic of the Congo) and defined PAD as an ABI of less than 0.9. They reported a PAD prevalence of 15%: 12% in Central African Republic and 17% in the Republic of the Congo. The prevalence was higher in urban Brazzaville compared with the rural area of Gamboma in the Republic of Congo (21% vs 14%, P = .01). However, there was no significant urban/rural difference in the Central African Republic (12% vs 13%, P > .05). Ngoungou et al23 also examined rural populations. Adults aged 40 years or older in Ntoum, Gabon, were exhaustively sampled to determine the prevalence of CVD. The survey used the Edinburgh Claudication Questionnaire (ECQ) and physical examination to assess for PAD; ABIs were not calculated. Of the 736 participants, none had definite claudication by the ECQ measure and 19 (2.7%) had possible claudication. Based on absent distal pulses, 25 participants (3%) had PAD. Koopman et al27 found a similarly low prevalence of PAD in a rural population in Ghana. Their study used a registry established in 2002 for parasite surveillance among persons living in the Garu-Tempane district.28 The registry included 924 individuals older than 50 years who were sampled for a cross-sectional survey. In general, they found that the prevalence of CVD risk factors was low in this population, including among those who were overweight (0.2% of men and 1.4% of women), had diabetes (1.0% of men and 1.4% of women), had dyslipidemia (1.1% of men and 1.7% of women), and/or had hypertension (16.7% of men and 13.7% of women). The total prevalence of PAD was 3.1% (2.3% of men [95% CI, 1.3%-4.1%] and 3.4% of women [95% CI, 2.1%-5.5%]). Finally, Fowkes et al29 measured ABI in 322 of 526 adults who were randomly sampled from Agincourt, a community in rural northeast South Africa. Their sample was predominately female (78%) owing to labor dynamics in the region. Although mean ABI was normal in both women and men (1.04 and 1.05, respectively), a significant trend of decreasing ABI with age was noted. More than 25% of participants older than 60 years and almost 40% of participants older than 70 years had an ABI less than 0.9. Clinical Cohorts Okello et al20 sampled 229 patients with diabetes older than 50 years from the outpatient diabetes clinic at Mbarara Regional Referral Hospital in Southwestern Uganda. They calculated ABI and administered the ECQ. Most patients had been diagnosed as having diabetes for at least 1 year and had a median hemoglobin A1c level of 8.1% (interquartile range, 6.7%-10.1%) (to convert to proportion of total hemoglobin, multiply by 0.01). By ABI, the prevalence of PAD was 24%. Fifty-six percent of patients with PAD were asymptomatic as evaluated by the ECQ. Only 11% of patients with an ABI of less than 0.9 were taking an aspirin and only 1 patient was taking a statin. In South Africa, Kumar et al30 quasi-randomly selected 542 outpatients presenting to Mthatha General Hospital. Inclusion criteria included age older than 50 years and no prior diagnosis of PAD. The prevalence of undiagnosed PAD was 29%. Risk factors differed by sex: men were more likely to be smokers and women were more likely to be obese and/or have diabetes. At a teaching hospital in Kampala, Uganda, Mwebaze et al11 quasi-randomly enrolled 146 patients from an outpatient diabetes clinic. Patients were eligible if they were older than 35 years and had been patients at the clinic for more than 1 year. Based on ABI, 39% of participants had PAD; this decreased to 23% based on pulse examination alone. Comparing ABI with results from the ECQ, 48% of patients with definite claudication by ECQ had a normal ABI. Peripheral arterial disease was asymptomatic in 41% of participants. Only 12% of patients were taking statin therapy, and 22% were taking antiplatelet agents. Oyelade et al31 conducted a survey at Baptist Medical Centre, a referral center in Ogbomoso, Nigeria. Participants were drawn randomly from adult patients with diabetes older than 50 years who attended the outpatient department between October 2009 and April 2010; 219 participants were recruited. The prevalence of PAD based on ABI was 53%. By history of intermittent claudication, prevalence was 25%. Prevalence decreased to 11% by absent pedal pulses on physical examination. As in other studies, PAD prevalence increased with age: 44% of patients between 50 years and 59 years had PAD whereas 86% of patients older than 80 years had PAD. Vascular Surgical Case Series Our search returned 5 reports, all case series, regarding the surgical management of vascular pathology. Adeoye et al32 described 14 peripheral vascular cases over a 2-year period at the University of Ilorin Teaching Hospital in Nigeria. Trauma accounted for more than 70% of the cases (11 of 14 cases). Other indications for surgery included dialysis access (1 of 14 cases), nontraumatic lower extremity aneurysm (2 of 14), and neoplasm (1 of 14). Similarly, Edaigbini et al33 described their experience from 2008 to 2012 at Ahmadu Bello University in Zaria, Nigeria. Over that time, 73 patients ranging in age from 1 to 90 years had vascular pathology medically or surgically managed, and 56 operations were performed. The most common indications for surgery were dialysis access (38 of 54 cases), trauma (10 of 54), and posttraumatic fistulae or pseudoaneurysms (4 of 54). Eleven patients with traditional atherosclerotic diseases (PAD [n = 5] and abdominal aortic aneurysm, [n = 6]) were treated nonoperatively owing to inadequate facilities, resources, and/or experience according to the authors. The remaining 3 series focused on indications for limb amputation in Tanzania,34 Nigeria,35 and Kenya.36 Chalya et al34 reviewed records from 162 patients who underwent major limb amputation at Bugando Medical Centre in Tanzania between March 2008 and February 2010. More than 80% of the amputations during the study were for either complications of diabetic foot ulcers (42%) or trauma (38%). Nondiabetic PAD accounted for 8.6% of the cases (14 of 162 cases). Similar findings were reported by Akiode et al35 who audited amputations of 71 limbs in 69 patients from 1998 to 2003 in Nigeria. Trauma accounted for 76% of all amputations (54 of 71 cases). Diabetes-related gangrene was the most common nontraumatic indication, which accounted for 14% of amputations (10 of 71 cases). In contrast to these series from Tanzania and Nigeria, the most common indication for amputation at Kenyatta National Hospital in Nairobi, Kenya,36 was nondiabetic PAD (28 of 74 cases, 38%) followed by trauma (14 of 74 cases, 19%) and diabetic PAD (13 of 74 cases, 18%). Discussion This review aimed to describe reports of PAD prevalence and management in sub-Saharan Africa. Estimates of PAD prevalence were reported from 10 countries. Reports documented a high PAD prevalence, ranging from 3.1% to 24% of older adults from community-based surveys and 39% to 52% of those with known risk factors (eg, diabetes). Few studies reported either medical or surgical management of PAD in sub-Saharan Africa. Together, these findings suggest a significant burden of PAD in sub-Saharan Africa, most of which remains undiagnosed and untreated owing to insufficient awareness and capacity. To put these findings into context, the international Reduction of Atherothrombosis for Continued Health Registry, which enrolled patients older than 45 years worldwide, reported an overall PAD prevalence of 15%, with estimates ranging from 6% in Asia to 24% in Western Europe.37 In a group of high-risk patients in France, investigators reported PAD prevalence to be 28% (95% CI, 27%-29%).38 The findings from community-based surveys in sub-Saharan Africa are similar or higher than the Reduction of Atherothrombosis for Continued Health Registry estimates. However, the prevalence among known risk groups was significantly higher. This could be related, in part, to poor primary and secondary prevention, evidenced by the lack of appropriate medical management and paucity of surgical reports retrieved. Multiple investigators studying PAD in HICs have observed an increased prevalence in both nonwhite39 and non-Hispanic black populations,39-42 even after controlling for risk factors such as hypertension and diabetes. The higher overall prevalence reported in high-risk sub-Saharan Africa patients relative to high-risk groups elsewhere is likely multifactorial in origin, but may also be related to the racial and ethnic differences observed in HICs. A 2013 meta-analysis also highlighted the differential effect of traditional cardiovascular risk factors on PAD prevalence in HICs vs LMICs, noting that the traditional risk factors were stronger predictors of risk in HICs than in LMICs.6 This raises the possibility that there may be other undetermined risk or epigenetic factors that may play a role in the observed discrepancy in PAD prevalence between regions such as human immunodeficiency virus (HIV)–associated vasculopathy.6,10 Numerous studies demonstrate a link between both HIV infection and HIV treatment and increased PAD risk43-49; however, only a few are specific to sub-Saharan Africa.10,50-52 Only 1 of the reports in this study incorporated HIV status.20 Consequently, the association between HIV prevalence and PAD in sub-Saharan Africa is unclear, but could have significant implications for screening and treatment. Therefore, more robust epidemiological studies are needed to clearly document the PAD burden and potentially identify these risk factors so that targeted interventions might be developed. Few records examined the effect of traditional atherosclerotic risk factors on the odds of having PAD. Furthermore, these estimates were often underpowered and varied considerably. Some reports were even contradictory. Overall, the trend for several risk factors was consistent with the largest meta-analysis to our knowledge examining PAD risk in LMICs (Figure 2).6 Consistent with existing literature,6,53,54 the findings from the retrieved reports also suggest that age is a predominant risk factor for PAD in sub-Saharan Africa. Extrapolating to risk at the city or country level, those locations within sub-Saharan Africa with the longest life expectancy are likely to have the largest burden of PAD. The PAD burden will likely increase at a rate proportional to the increases in life expectancy anticipated across the continent.55 Urbanization and economic development in sub-Saharan Africa are linked to both age and chronic disease risk factor exposure. Specifically, more urban and higher-income populations are likely to have both longer life expectancy and greater (both in magnitude and duration) exposure to risk factors such as obesity and smoking. This extends the findings of other authors who have explored the role of urbanization and changes in CVD risk in Africa56 and other LMICs more broadly.57 To blunt the effect of the epidemiological transition, the World Health Organization has set a target to reduce deaths caused by noncommunicable disease in people younger than 70 years by 25% by 2025 through investing in cost-effective “best-buy” interventions. These include cigarette tax increases, increasing public awareness of the benefits of healthy diet and exercise, and providing multidrug therapy to those at high risk for or with CVD.58 In addition to mitigating the future CVD burden in LMICs, the cost benefits are estimated to be more than US $375 billion by 2025.59 Furthermore, given that PAD is often the presenting condition for individuals with undiagnosed diabetes or CVD, improving the recognition of PAD by health workers may strengthen secondary prevention efforts in sub-Saharan Africa, including guideline development and dissemination.9,12 Reports repeatedly described significant discrepancies and low sensitivity of non-ABI measures to diagnose PAD compared with ECQ and physical examination. Studies that used multiple methods to evaluate for PAD suggest that any technique other than ABI, including history with physical examination, are likely to underdiagnose PAD owing to the combination of insensitive techniques and a high frequency of asymptomatic disease. This is consistent with findings described previously in HICs.6,39,60 Therefore, future prevalence studies in sub-Saharan Africa should use ABI measurement to estimate PAD. No record in our study examined the effect of low ABI on overall cardiovascular risk; however, an extensive body of literature from HICs has robustly demonstrated that many patients without symptoms but abnormal ABIs have an increased risk of all-cause cardiac mortality compared with patients with normal ABIs.61-64 With this in mind, it is concerning that no report in our study described adequate treatment of PAD with aspirin or statin therapy; the reports by Okello et al20 and Mwebaze and Kilbirige11 found that only 10% to 22% of patients with an ABI of less than 0.9 were receiving antiplatelet therapy and 2% to 12% of patients were receiving statin therapy. The implications for screening high-risk populations are clear: clinicians must be supplied with the training and tools needed to perform reliable ABI measurements if they provide care to high-risk populations in sub-Saharan Africa. Arguably, the greatest benefit of understanding PAD prevalence has more to do with primary prevention of all-cause cardiac mortality than the management of critical limb ischemia or symptomatic PAD. Therefore, screening and management of PAD is directly in line with several World Health Organization Noncommunicable Disease Global Action Plan objectives.3,65 Moreover, there will be considerable opportunities for limb salvage and prevention of disseminated infection through prompt surgical management of PAD if health systems are adequately resourced to care for the impending burden. Surgeons trained in Africa may receive little exposure to vascular surgery, and much of that exposure is related to traumatic injury or other emergent indications.14,15,66,67 Additionally, surgical indications for amputation differ between communities. This highlights the importance of understanding locoregional epidemiology to strategically build capacity where need is greatest. Additional studies in this area will need to systematically evaluate the epidemiology of PAD in sub-Saharan Africa; define essential vascular care, which should include prevention initiatives; assess the capacity to deliver such care; and demonstrate the effect of essential vascular care on CVD and/or PAD outcomes. This review had several limitations. First, more than half of the reports determined PAD prevalence among clinically based populations; thus, they are not representative of the population at large. Although these studies cannot be used to estimate population prevalence, they do provide valuable information on specific high-risk groups such as patients with diabetes or known CVD. Second, the results for the retrieved reports are difficult to compare given different definitions of PAD and methods by which PAD was diagnosed. However, this limitation highlights the importance of using a standard case definition and technique when reporting estimates of PAD prevalence. Last, a detailed examination of risk factors and their effect on PAD prevalence exceeded the scope of this review. However, this is critical to understanding and forecasting the burden of PAD in sub-Saharan Africa. Despite these limitations, this review highlights the potentially significant burden of PAD in sub-Saharan Africa and the lack of epidemiological understanding and the preparedness for its management. Conclusions The prevalence of PAD in sub-Saharan Africa appears to follow the pattern of CVD risk factor exposure. In those areas still primarily affected by infectious disease and minimal exposure to traditional CVD risk factors, prevalence may be low; however, in areas with progressive urbanization, longer life expectancy, and more exposure to CVD risk factors, prevalence is equal to or higher than that seen in HICs. In high-risk populations, prevalence has been reported to exceed 50%. To further define the epidemiology of PAD in sub-Saharan Africa, research teams should consider community-based surveys and ABI measurement. Use of claudication history with physical examination is inadequate. Three major areas of intervention are needed. First, all primary clinicians should be made aware of the major risk factors for PAD and provided the necessary training and tools to diagnose PAD early. Second, the importance of secondary prevention, including smoking cessation, hypertension control, and aspirin and statin therapy in patients with PAD or CVD, must be emphasized to all clinicians. Third, efforts to expand vascular care capacity in treating PAD must begin now to meet the growing demand. Back to top Article Information Corresponding Author: Lily E. Johnston, MD, MPH, Department of Surgery, University of Virginia Medical Center, PO Box 800681, Charlottesville, VA 22908-0681 (lj6p@virginia.edu). Accepted for Publication: January 8, 2016. Published Online: April 6, 2016. doi:10.1001/jamasurg.2016.0446. Author Contributions: Drs Johnston and Kushner had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Johnston, Stewart, Upchurch, Gyedu, Kushner. Acquisition, analysis, or interpretation of data: Johnston, Stewart, Yangni-Angate, Veller, Upchurch, Gyedu, Kushner. Drafting of the manuscript: Johnston, Stewart. Critical revision of the manuscript for important intellectual content: Johnston, Stewart, Yangni-Angate, Veller, Upchurch, Gyedu, Kushner. Statistical analysis: Johnston. Obtained funding: Stewart. Administrative, technical, or material support: Gyedu, Kushner. Study supervision: Yangni-Angate, Upchurch. Conflict of Interest Disclosures: None reported. Funding/Support: This study was funded in part by grant R25TW009345 from the Fogarty International Center, US National Institutes of Health, and by grant UM1 HL088925 from the Network for Cardiothoracic Surgical Investigations in Cardiovascular Medicine. Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. References 1. Beaglehole R, Bonita R, Alleyne G, et al; Lancet NCD Action Group. UN high-level meeting on non-communicable diseases: addressing four questions. Lancet. 2011;378(9789):449-455.PubMedGoogle ScholarCrossref 2. Beaglehole R, Bonita R, Horton R, et al; Lancet NCD Action Group; NCD Alliance. 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JAMA Surgery – American Medical Association
Published: Jun 1, 2016
Keywords: peripheral vascular diseases,cardiovascular disease risk factors,africa south of the sahara,surgical procedures, operative,vascular surgical procedures,prevalence,peripheral artery,diabetes mellitus,epidemiology,screening,wounds and injuries
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