Martin Veller

The BEST study--a prospective study to compare business class versus economy class air travel as a cause of thrombosis.

BACKGROUND As many as 10% of airline passengers travelling without prophylaxis for long distances may develop a venous thrombosis. There is, however, no evidence that economy class travellers are at increased risk of thrombosis. OBJECTIVES A suitably powered prospective study, based on the incidence of deep-vein thrombosis (DVT) reported in previous studies on long-haul flights, was designed to determine the incidence of positive venous duplex scans and D-dimer elevations in low and intermediate-risk passengers, comparing passengers travelling in business and economy class. PATIENTS/METHODS Eight hundred and ninety-nine passengers were recruited (180 travelling business class and 719 travelling economy). D-dimers were measured before and after the flight. A value greater than 500 ng/ml was accepted as abnormal. A thrombophilia screen was conducted which included the factor V Leiden mutation, the prothombin 20210A mutation, protein C and S levels, antithrombin levels, and anticardiolipin antibodies immunoglobulin G (IgG) and immunoglobulin M (IgM). On arrival, lower limb compression ultrasonography of the deep veins was performed. Logistical regression analysis was used to determine the risk factors related to abnormally high D-dimer levels. RESULTS Only 434 subjects had a full venous duplex scan performed. None had ultrasonic evidence of venous thrombosis. Nine passengers tested at departure had elevated D-dimer levels and these volunteers were excluded from further study. Seventy-four of the 899 passengers had raised D-dimers on arrival. Twenty-two of 180 business class passengers (12%) developed elevated D-dimers compared with 52 of 719 economy class passengers (7%). There was no significant association between elevation of D-dimers and the class flown (odds ratio (OR) 0.61, p = 0.109). The factor V Leiden mutation, factor VIII levels and the use of aspirin were, however, associated with raised D-dimers (OR 3.36, p = 0.024; OR 1.01, p = 0.014; and OR 2.04, p = 0.038, respectively). Five hundred and five passengers were contacted within 6 months and none reported any symptoms of a clinical thrombosis or pulmonary embolus. CONCLUSION The incidence of ultrasonically proven DVT is much lower than previously reported. However, more than 10% of all passengers developed raised D-dimers, which were unrelated to the class flown. A rise in D-dimers is associated with an inherent risk of thrombosis and/or thrombophilia, demonstrates activation of both the coagulation and fibrinolytic systems during long-haul flights, and may indicate the development of small thrombi.

Brachial blood pressure-independent relations between radial late systolic shoulder-derived aortic pressures and target organ changes.

Central aortic blood pressure (BP; BPc) predicts outcomes beyond brachial BP. In this regard, the application of a generalized transfer function (GTF) to radial pulse waves for the derivation of BPc is an easy and reproducible measurement technique. However, the use of the GTF may not be appropriate in all circumstances. Although the peak of the second shoulder of the radial waveform (P2) is closely associated with BPc, and, hence, BPc may be assessed without the need for a GTF, whether P2-derived BPc is associated with adverse cardiovascular changes independent of brachial BP is uncertain. Thus, P2- and GTF-derived aortic BPs were assessed using applanation tonometry and SphygmoCor software. Left ventricular mass was indexed for height1.7 (n=678) and carotid intima-media thickness (IMT; n=462) was determined using echocardiography and vascular ultrasound. With adjustments for nurse-derived brachial pulse pressure (PP), P2-derived central PP was independently associated with left ventricular mass indexed for height1.7 (partial r=0.18; P<0.0001) and IMT (partial r=0.40; P<0.0001). These relations were similar to nurse-derived brachial PP-independent relations between GTF-derived central PP and target organ changes (left ventricular mass indexed for height1.7: partial r=0.17, P<0.0001; IMT: partial r=0.37, P<0.0001). In contrast, with adjustments for central PP, nurse-derived brachial PP-target organ relations were eliminated (partial r=−0.21 to 0.05). Twenty-four–hour, day, and night PP-target organ relations did not survive adjustments for nurse-derived brachial BP. In conclusion, central PP derived from P2, which does not require a GTF, is associated with cardiovascular target organ changes independent of brachial BP. Thus, when assessing adverse cardiovascular effects of aortic BP independent of brachial BP, P2-derived measures may complement GTF-derived measures of aortic BP.

Assessment of the medial head of the gastrocnemius muscle in functional compression of the popliteal artery

OBJECTIVE Nonfunctional popliteal entrapment is due to embryologic maldevelopment within the popliteal fossa. Functional entrapment occurs in the apparent absence of an anatomic abnormality. Gastrocnemius hypertrophy has been associated with the latter. Both forms of entrapment may cause arterial injury and lower limb ischemia. This study assessed the attachment of the medial head of the gastrocnemius muscle in healthy occluders and healthy nonoccluders. METHODS Provocative tests were used to identify 58 nonoccluders and 16 occluders. Ten subjects from each group underwent magnetic resonance imaging evaluation of the popliteal fossa. The medial head of the gastrocnemius muscle attachment was assessed in the supracondylar, pericondylar, and intercondylar areas. RESULTS In the occluder group, significantly more muscle was attached towards the femoral midline (supracondylar), around the lateral border of the medial condyle (pericondylar), and within the intercondylar fossa. CONCLUSION The more extensive midline position of the medial head of the gastrocnemius in occluders is likely to be a normal embryological variation. Forceful contraction results in compression and occlusion of the adjacent popliteal artery. The clinical significance of these anatomic variations remains unclear. However, these new observations may provide insight for future analysis of the causes and natural history of functional compression and the potential progression to clinical entrapment.

Efficacy of vitamin E compared with either Simvastatin or Atorvastatin in preventing the progression of atherosclerosis in homozygous familial hypercholesterolemia

Over a 4-year period, antioxidant therapy (vitamin E) was compared with high-dose statin therapy in 15 patients with homozygous familial hypercholesterolemia. Carotid intima-media thickness, used as an in vivo assessment of atherosclerosis, progressed rapidly during the period of vitamin E therapy but regressed on statin therapy.

A Mismatch Between Aortic Pulse Pressure and Pulse Wave Velocity Predicts Advanced Peripheral Arterial Disease

OBJECTIVES To determine whether increases in central aortic pulse pressure (PPc), but decreases in carotid-femoral pulse wave velocity (PWV) predict the presence of advanced peripheral arterial disease (PAD). METHODS Applanation tonometry and vascular ultrasound were employed to assess carotid-femoral PWV, PPc, and carotid intima media thickness (IMT) in 136 patients of African ancestry with chronic critical lower limb ischaemia (CLI) and in 1,030 randomly selected healthy adults of African ancestry, 194 of whom were age- and sex matched (controls). RESULTS With adjustments for confounders, compared with age- and sex-matched controls, participants with CLI had an increased carotid IMT (p = .0001) and PPc (p < .0001), but a markedly reduced PWV (m/second) (CLI = 5.7 ± 3.7, controls = 8.6 ± 3.4, p < .0001). PWV was correlated with PPc in controls (r = .52, p < .0001), but not in CLI (r = -.06). A PPc/PWV mismatch index showed increased values in participants with CLI over the full adult age range assessed. With carotid IMT, PPc, or aortic augmentation index in the same regression model, an increase in the PPc/PWV mismatch index was independently associated with CLI (p < .0001) and a PPc/PWV value upper 95% confidence interval in the community sample predicted CLI (odds ratio = 32 [6-169], p < .0001). PPc/PWV predicted CLI with a similar level of performance and accuracy and a greater specificity (98%) than that of IMT (82%). CONCLUSION In CLI, while PPc increases, carotid-femoral PWV is markedly reduced. A PPc/PWV mismatch may be a new risk marker for advanced PAD.

Surgical Education in South Africa

Medical training has been well established in South Africa since the 1920s. This was initially undergraduate only, and specialist training required study overseas until the early 1960s. The first formal specialist training circuits were developed in conjunction with the formation of the Colleges of Medicine of South Africa (CMSA) in 1955, which was established largely as an examination body to oversee standards of training. Since then the member colleges of the CMSA regulate the standards of training and examinations of General Surgery, Orthopaedics, Urology, Cardiothoracic Surgery, Neurosurgery, Plastic and Reconstructive Surgery, Ear, Nose and Throat Surgery, Ophthalmology, and Obstetrics and Gynaecology, as well as the nonsurgical disciplines. A variety of bodies are responsible for the different stages of training. The universities train undergraduates and award the first degree (e.g., MB, BCh). This is followed by a two-year internship in all the major disciplines in a hospital accredited by the Health Professions Council of South Africa (HPCSA), and one year of community service (usually in relatively unsupervised rural hospitals), overseen by the state’s Department of Health. On completing these three years, the doctor is fully registered with the HPCSA as a medical practitioner. The Colleges are primarily a professional examining body and oversee subsequent postgraduate training which must be accredited by the HPCSA. Training in general surgery is delegated by the College to the academic surgical departments of the eight medical schools of South Africa [Witwatersrand, Cape Town, Stellenbosch, Nelson Mandela (Durban), Medunsa/Limpopo (Garankua), Walter Sisulu (Mthatha), Pretoria and Bloemfontein], where it occurs in the teaching hospitals of each university. There are differences in the training depending on the school, but each candidate must be a registrar (resident) for not less than four years (most require six years), must pass the College examinations [the Fellowship of the College of Surgeons of South Africa, or FCS(SA)], or, alternatively, an internal, university-specific MMed examination [similar to the FCS(SA)], and demonstrate (through a logbook and a report from their department head) sufficient practical experience to be registered as a specialist surgeon by the HPCSA. The examination for the Fellowship in General Surgery comprises three parts: Primary, Intermediate, and Final.

Large vessel adventitial vasculitis characterizes patients with critical lower limb ischemia with as compared to without human immunodeficiency virus infection.

Objectives Whether a human immunodeficiency virus (HIV)-associated vasculitis in-part accounts for occlusive large artery disease remains uncertain. We aimed to identify the histopathological features that characterize large vessel changes in HIV sero-positive as compared to sero-negative patients with critical lower limb ischemia (CLI). Materials and Methods Femoral arteries obtained from 10 HIV positive and 10 HIV negative black African male patients admitted to a single vascular unit with CLI requiring above knee amputation were subjected to histopathological assessment. None of the HIV positive patients were receiving antiretroviral therapy. Results As compared to HIV negative patients with CLI, HIV positive patients were younger (p<0.01) and had a lower prevalence of hypertension (10 vs 90%, p<0.005) and diabetes mellitus (0 vs 50%, p<0.05), but a similar proportion of patients previously or currently smoked (80 vs 60%). 90% of HIV positive patients, but no HIV negative patient had evidence of adventitial leukocytoclastic vasculitis of the vasa vasorum (p<0.0001). In addition, 70% of HIV positive, but no HIV negative patient had evidence of adventitial slit-like vessels. Whilst T-lymphocytes were noted in the adventitia in 80% of HIV positive patients, T-lymphocytes were noted only in the intima in HIV negative patients. The presence of femoral artery calcified multilayered fibro-atheroma was noted in 40% of HIV positive and 90% of HIV negative patients with CLI. Conclusions An adventitial vasculitis which characterizes large artery changes in CLI in HIV-infected as compared to non-infected patients, may contribute toward HIV-associated occlusive large artery disease.

Carotid Intima-Media Thickness in African Patients with Critical Lower Limb Ischemia Infected with the Human Immunodeficiency Virus

Background: The extent to which Human Immunodeficiency Virus (HIV) is associated with increases in carotid Intima-Media Thickness (IMT) independent of conventional cardiovascular risk factors is unclear. Hence, we evaluated whether independent of conventional risk factors, an increased carotid IMT occurs in African HIV infected patients with chronic Critical Limb Ischemia (CLI). Methods: Carotid IMT was measured in 217 sequentially recruited patients with CLI, 25 of whom were HIV positive and in 430 randomly selected controls from a community sample. Results: As compared to HIV negative patients with CLI, HIV positive patients were younger (49 ± 10 vs. 64 ± 11 years, p<0.0001) and had a markedly lower prevalence of hypertension and diabetes mellitus (p<0.0001), but a similar proportion of patients smoked (76% vs 67%). However, as compared to patients with CLI who were HIV negative, HIV positive patients had a similar increase in carotid IMT (HIV positive= 0.75 ± 0.14 mm; HIV negative= 0.79 ± 0.14 mm; Controls= 0.64 ± 0.15, p < 0.0001 versus Controls) even after adjustments for age, sex and conventional risk factors (HIV positive= 0.75 ± 0.13 mm; HIV negative=0.73 ± 0.15 mm, Controls=0.66 ± 0.15, p < 0.005). IMT was similarly increased in HIV positive patients with CLI as compared to controls when assessed in men, smokers, and black African patients only (p < 0.05-0.0001), or in those who were receiving highly active antiretroviral therapy (n=12, 0.74 ± 0.10 mm) as compared to those not receiving therapy (0.75 ± 0.15 mm). As compared to controls, the age- sex- and conventional risk factor-adjusted odds of having an IMT ≥ 0.8 mm was similarly increased in patients with CLI who were HIV positive (odds ratio= 8.89, CI= 2.79-28.32, p= 0.0002) as those who were HIV negative (odds ratio= 2.70 CI= 1.51-4.81, p < 0.001). Conclusion: These results suggest that despite being of a younger age, with or without conventional risk factor adjustments, marked increases in carotid IMT in HIV in Africa are a risk factor for CLI.

Peripheral Arterial Disease in Sub-Saharan Africa: A Review.

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.

Vascular surgical education in a medium-income country.

Medium income country such as South Africa face a dilemma on the need to offer high quality vascular surgical care in a resource constrained environment, where the vast majority of population has inadequate access to even the most basic health care provision. At the same time with rapid development in technology there is also the need to provide high technological treatment to a small population that can afford high cost therapy. This apparent dichotomy in health care provides a challenge and the solution is for all role players in the health care provision to find a solution which will suite the population at large.