The role of conventional echocardiographic parameters on detecting subclinical anthracycline therapy related cardiac dysfunction-The SATRACD study.

Background: Subclinical anthracycline therapy related cardiac dysfunction (ATRCD) can be detected with speckle tracking echocardiographic image (STE), which is not widely available in Uganda. We aimed to investigate the role of the two conventional echocardiographic parameters [mitral annular plane systolic excursion (MAPSE) and mitral annular peak systolic tissue Doppler velocity (S')] on diagnosing subclinical ATRCD. Method and results: 207 cancer patients who underwent anthracycline based chemotherapy were recruited at baseline and followed up until 6 months after ending anthracycline therapy. Comprehensive echocardiographic data were collected at each visit. Global longitudinal strain (GLS) by STE was used as the gold standard diagnostic test to define the case of subclinical ATRCD. Data of the 200 patients who had no evidence of clinical ATRCD were analyzed. One hundred and seventy-two (86.0%) were female, with a median age of 42 years and 47 (23.5%) patients were diagnosed with subclinical ATRCD at the end of anthracycline therapy by GLS criteria. The area under the curve (AUC), cutoff point, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of reduction of MAPSE (ΔMAPSE) were 0.6736 (95% CI: 0.5885, 0.7587), ≥ 2 mm, 74.5% (95% CI: 59.7%, 86.1%), 54.9% (95% CI: 46.7%, 63.0%), 33.7% (95% CI: 24.7%, 43.6%), and 87.5% (95% CI: 79.2%, 93.4%). The AUC, cutoff point, sensitivity, specificity, PPV, and NPV of reduction of S' (ΔS') were 0.6018 (95% CI: 0.5084, 0.6953), ≥ 0.5 cm/s, 61.7% (95% CI: 46.4%, 75.5%), 52.7% (95% CI: 44.4%, 60.9%), 29.0% (95% CI: 20.4%, 38.9%), and 76.1% (95% CI: 72.4%, 88.6%). When ΔMAPSE and ΔS' are used as parallel test, the net sensitivity and specificity is 89.4% and 28.8%, respectively, the net PPV and NPV is 27.8% and 90.0%, respectively. Conclusion: The ΔMAPSE and ΔS' showed fairly good accuracy, sensitivity and NPV to detect subclinical ATRCD in Ugandan cancer patients. These conventional echocardiographic parameters may serve as screening tools for detecting subclinical ATRCD in resource limited settings.

Detecting subclinical anthracycline therapy-related cardiac dysfunction in patients attending Uganda Cancer Institute.

Aims: To investigate the incidence of anthracycline therapy-related cardiac dysfunction (ATRCD) and its predictors among Ugandan cancer patients. Patients & methods: The study recruited 207 cancer patients who were followed for 6 months after ending anthracycline therapy. Global longitudinal strain and troponin-I were the diagnostic tools. Results & conclusions: The cumulative incidences of subclinical and clinical ATRCD were 35.0 and 8.8% respectively. The predictors of clinical ATRCD were HIV infection (hazard ratio [HR]: 3.04; 95% CI: 1.26-7.32; p = 0.013), lower baseline global longitudinal strain (HR: 0.61; 95% CI: 0.53-0.71; p < 0.001) and development of subclinical ATRCD at the end of anthracycline therapy (HR: 6.61; 95% CI: 2.60-16.82; p < 0.001). Cardiac surveillance at baseline and at ending of anthracycline therapy is essential to identify high-risk patients.

Anthracyclines are drugs for treating many types of cancers. They may however be harmful to the heart. This anthracycline side effect will first cause subtle heart­cell injury that can be detected and treated if it is handled early. Therefore, this study aims to study patients in the Uganda Cancer Institute to find out how many patients can get and who are likely to get this side effect. We found that 35% of the patients had subtle heart­cell injury and 8.8% had a more severe form of heart­cell injury. The patients who lived with HIV, whose heart was weaker and who got subtle heart­cell injury immediately after treatment were more likely to get the severe form of the side effect. Patients who receive anthracycline therapy need to be monitored closely to prevent serious heart injury.

Rational and design of SATRACD study: detecting subclinical anthracycline therapy related cardiac dysfunction in low income country.

BACKGROUND: Anthracycline therapy-related cardiac dysfunction (ATRCD) is the most notorious adverse side-effect of chemotherapy. It has become a significant cardiovascular health concern for long-term cancer survivors. With the emerging concept of subclinical ATRCD and newer diagnostictools (Speckle Tracking Echocardiography (STE) and biomarkers), detecting anthracycline cardiac toxicity at an early stage has become an important step to prevent severe cardiac dysfunction and improve the cardiovascular outcome in cancer survivors. Despite the increasing population at risk in sub-Saharan Africa (SSA), there is no contemporary data in Uganda to address the burden, pathogenesis and risk factors of subclinical ATRCD. This big gap in knowledge has led to a lack of local guidelines for monitoring and management of ATRCD. METHODS: SATRACD (Detecting Subclinical Anthracycline Therapy Related Cardiac Dysfunction In Low Income Country) study is an observational prospective cohort study. Three hundred and fifty-three anthracycline naïve cancer patients will be recruited at baseline. Patients are followed up on completion of anthracycline-based chemotherapy and at 6 months after completion of anthracycline therapy. Data on demographics, cancer profile and clinical presentation will be collected at baseline. Comprehensive cardiac assessment will be performed at each visit, including electrocardiogram, conventional echocardiography, STE, cardiac and oxidative stress markers. We will be able to determine the incidence of subclinical and clinical ATRCD at 6 months after completion of anthracycline therapy, determine whether hypertension is a major risk factor for ATRCD, evaluate the role of conventional echocardiography parameters, and biomarkers for detecting subclinical ATRCD. CONCLUSION: This SATRACD study will provide contemporary data on Ugandan cancer patients who have subclinical and clinical ATRCD, help in the development of local strategies to prevent and manage ATRCD, and improve cardiovascular outcome for Ugandan cancer survivors.

Clinical characterization, cardiovascular risk factor profile and cardiac strain analysis in a Uganda cancer population: The SATRACD study.

BACKGROUND: The link between cancer and cardiovascular disease is firmly established. We sought to investigate the prevalence of cardiovascular disease (CVD) risk factors in Uganda cancer patients, their pre-chemotherapy left ventricular strain echocardiographic pattern and its associations with the CVD risk factors. METHODS AND RESULTS: Baseline pre-chemotherapy data of patients who were enrolled in the SATRACD study (a cancer cohort, who were planned for anthracycline therapy), were analyzed. The prevalence of cardiovascular risk factors and baseline strain echocardiographic images were assessed. Among the 355 patients who were recruited over a period of 15 months, 283 (79.7%) were female, with a mean age of 43 years. The types of cancer of the study patients included breast cancer (70.6%), lymphomas, sarcomas, leukemias and hepatocellular carcinoma. Hypertension was the most common comorbidity (27.0%). The prevalence of obesity was 12.1% and that of HIV was 18.3%. All patients had a normal left ventricular ejection fraction (LVEF). The mean global longitudinal strain (GLS) was -20.92 ±2.43%, with females having a significantly higher GLS than males (-21.09±2.42 vs -20.25±2.39, p = 0.008). Fifty-three patients (14.9%) had suboptimal GLS (absolute GLS≤18.00%), which was associated with obesity (POR = 3.07; 95% CI, 1.31-6.98; p = 0.003), alcohol use (POR = 1.94; 95% CI, 1.01-3.74; p = 0.044), long QTc interval in electrocardiogram (POR = 2.54; 95% CI, 1.06-5.74; p = 0.015,) and impaired left ventricular relaxation (POR = 2.24; 95% CI, 1.17-4.25; p = 0.007). On multivariable logistic regression analysis, obesity (POR = 2.95; 95% CI, 1.24-7.03; p = 0.014) was the only independent factor associated with suboptimal GLS. CONCLUSION: There is high prevalence and a unique pattern of cardiovascular risk factors in Uganda cancer patients. In cancer patients with cardiovascular risk conditions, there is reduction in GLS despite preserved LVEF. Longitudinal research is needed to study the predictive value of cardiovascular risk factors and baseline GLS for post chemotherapy cardiac dysfunction.

Kidney disease in Uganda: a community based study.

BACKGROUND: Chronic kidney disease (CKD) is a major cause of morbidity and mortality in Sub-Saharan Africa (SSA). The majority of studies on CKD in SSA have been conducted among HIV-infected populations and mainly from large health facilities. We determined the prevalence of CKD and its predictors among populations in communities in central Uganda. METHODS: A cross-sectional study was conducted in Wakiso district using multi-stage sampling. Data was collected on age, sex, socio-economic status, history of alcohol intake, diabetes mellitus, hypertension and smoking. Measurement of blood pressure, weight and height to determine body mass index (BMI) and investigations including HIV testing, fasting blood sugar, creatinine and urinalysis were conducted. Logistic regression was used to estimate the strength of the association between variables and the presence of CKD estimated using the Cockcroft Gault formula. RESULTS: A total of 955 participants aged 18-87 years were enrolled into the study. The median age was 31 years (Interquartile range 24-42) and majority (67%) were female. Up to 21.4% (204/955) had abnormal renal function with CKD stage 1 in 6.2% (59/955), stage 2 in 12.7% (121/955), stage 3 in 2.4% (23/955), CKD stage 4 in 0% and CKD stage 5 in 0.1% (1/995). Female gender OR 1.8 (95% Confidence Interval [CI] 1.2-2.8), age >30 years OR 2.2(95% CI 1.2-3.8) and high social economic status OR 2.1 (95% CI 1.3-3.6) were associated with increased risk of CKD while BMI > 25Kg/m2 was protective against CKD OR 0.1 (95% CI 0.04-0.2). Traditional risk factors such as HIV-infection, diabetes mellitus, smoking and alcohol intake were not found to be significantly associated with CKD. CONCLUSION: We found a high prevalence of kidney disease in central Uganda. Interestingly the traditional risk factors associated with CKD previously documented, were not associated with CKD.

Determinants of Raised Blood Pressure in Urban Uganda: A Community-Based Case-Control Study.

OBJECTIVE: Rapid urbanization is changing the epidemiology of non-communicable diseases in sub-Saharan Africa. We aimed to identify the determinants of raised blood pressure in urban Uganda to highlight targets for preventive interventions. DESIGN: Case-control. SETTING: Three community-based sites in Kampala, the capital of Uganda. PARTICIPANTS: Participants were eligible to enroll if they were aged ≥18 years and not pregnant. METHODS: 450 cases with raised blood pressure were frequency matched by sex and age to 412 controls. Unconditional logistic regression was used to evaluate the association of socio-demographic, lifestyle, anthropometric, and laboratory variables with the outcome of raised blood pressure. Cases currently treated with antihypertensive medication and cases not treated with antihypertensive medication were analyzed separately. RESULTS: Significantly increased odds of raised blood pressure were associated with overweight body mass index (BMI) (25 kg/m2 ≤ BMI < 30 kg/m2), obese BMI (BMI ≥ 30 kg/m2) and hemoglobin A1c ≥ 6.5%. Significantly decreased odds of raised blood pressure were associated with moderate-to-vigorous work-related physical activity of >4 hours/week. No significant associations were found between raised blood pressure and marital status, education level, car or flush toilet ownership, dietary habits, alcohol consumption, smoking habits, moderate-to-vigorous leisure-related physical activity > 4 hours/week, waist-to-hip ratio, or total cholesterol levels. CONCLUSIONS: Targeted interventions are needed to address the key modifiable risk factors for raised blood pressure identified in this study, namely elevated BMI and regular physical activity, in order to reduce the burden of cardiovascular disease in urban Uganda.

A cross-sectional population survey on stroke knowledge and attitudes in Greater Kampala, Uganda.

BACKGROUND: Stroke is a neurological condition with rapidly increasing burden in many low- and middle income countries. Africa is particularly hard-hit due to rapid population growth, patterns of industrialization, adoption of harmful western diets, and increased prevalence of risk factors such as hypertension and obesity. Reducing stroke risk factors and teaching people to respond to stroke warning signs can prevent stroke and reduce burden. However, being able to address gaps in knowledge and improving both preventative and early-response care requires a clear understanding of practical and potentially modifiable topics. In this cross sectional study, we assessed the knowledge and attitudes among an urban population residing within the greater Kampala, Uganda. METHODS: A population cross sectional survey was conducted in urban Mukono, district, central Uganda. Through the systematic sampling method, data were gathered from 440 adult participants who were interviewed about selected aspects of stroke knowledge, attitudes and perception using a pretested structured questionnaire. RESULTS: A total of 440 study participants were enrolled. The leading risk factors for stroke identified by the participants were stress (75.7%) and hypertension (45.2%) respectively. Only two (0.5%) of the study participants identified cigarette smoking as a stroke risk factor. Individuals with hypertension have poor knowledge regarding stroke in spite their high risk for stroke. CONCLUSION: Stroke knowledge is poor while, stress and hypertension are the leading perceived risk factors in our settings. While stress is contributing factor, hypertension is likely a more amenable and practical intervention target. Targeting individuals with stroke risk factors to increase stroke knowledge and education is crucial for engagement in healthcare. Implementing a self-management program to support and motivate this high-risk group as well as adopting healthy life-styles may be a way to reduce stroke burden in Uganda.

Knowledge, attitudes and perceptions of stroke: a cross-sectional survey in rural and urban Uganda.

BACKGROUND: Information regarding the increasing burden of non-communicable diseases such as stroke is largely unknown among the vulnerable communities. This analysis, which is part of a larger U.S. National Institute of Heath-funded Medical Education Partnership Initiative neurological disorder survey, assessed community knowledge and attitudes on stroke and stroke risk factors. METHODS: A population cross-sectional survey was conducted in urban and rural Mukono, district, central Uganda. Through the systematic sampling method, data were gathered from 377 adult participants who were interviewed about selected aspects of stroke knowledge, attitudes and perception using a pretested structured questionnaire. RESULTS: A total of 377 participants were enrolled (47% urban). The leading risk factors identified by the participants were stress (36.6%) and hypertension (28.9%) respectively. None of the study participants identified cigarette smoking as a stroke risk factor. Seventy six percent of the participants did not recognize stroke as a disease of the brain. CONCLUSION: Stroke knowledge is poor in both rural and urban Uganda. Tailored public health approaches that improve stroke awareness, knowledge and self management approaches are urgently needed to develop effective preventive measures and community response to stroke.

Angiotensin II status and sympathetic activation among hypertensive patients in Uganda: a cross-sectional study.

BACKGROUND: Sympathetic activation and renin-angiotensin system are essential for development and sustenance of hypertension. However, the status of these systems has not been well evaluated among patients in an African setting. This study therefore set out to assess the angiotensin II status and sympathetic activation among hypertensive patients in Uganda. METHODS: In this cross sectional study conducted at Mulago, the national referral hospital, blood samples were taken to measure angiotensin II, metanephrines and normetanephrines. Urine samples were also taken for measuring urine creatinine and sodium. The angiotensin II categories were defined using the Mosby's Diagnostic and Laboratory Test References. 9th ed while the metanephrines and normetanephrine categories were defined using the Makerere University Biosafety II Immunology Laboratory reference values. RESULTS: 162 patients were consented and enrolled into the study, of these 136 (84 %) had low, 15 (9 %) had normal, while, 11 (7 %) had high angiotensin II levels. 142 (88 %) participants had normal levels of metanephrine, while 20 (12 %) had high levels. Only 88 were assessed for metanephrines and of these 85 (97 %) had normal, while 3 (3 %) had raised levels. Urine sodium was associated with low and normal angiotensin II levels (P value 0.007). Female gender and diastolic blood pressure were associated with a protective effect against high normetanephrines (OR 0.29, P value 0.015), 80-89 mmHg (OR 0.19, p value 0.053), above 100 mmHg (OR 0.27, p value 0.022). Current smoking status was associated with high risk for abnormal normetanephrines (OR 17.6, P value -0.022) while former smoking was associated with high risk for abnormal metanephrines (OR 18.7, p value 0.022). After multivariate analysis, all the significant variables at bivariate analysis were still significant except those who stopped smoking and those with a BP at 80-89 which were not significant. CONCLUSIONS: Hypertensive patients in this setting have predominantly low angiotensin II hypertension as a result of high salt intake. Sympathetic activation is not a significant mechanism of hypertension in this study population, more so in the females, with the exception of smokers who have a highly activated sympathetic system. Therefore, the use of agents targeting renin angiotensin and sympathetic systems as single first line antihypertensive agents in this setting should be re-evaluated if such patients are to be treated effectively.

Stroke-Risk Factors Differ between Rural and Urban Communities: Population Survey in Central Uganda.

BACKGROUND: Socioeconomic transition is changing stroke risk factors in Sub-Saharan Africa. This study assessed stroke-risk factors and their associated characteristics in urban and rural Uganda. METHODS: We surveyed 5,420 urban and rural participants and assessed the stroke-risk factor prevalence and socio-behavioural characteristics associated with risk factors. RESULTS: Rural participants were older with higher proportions of men and fewer poor compared to urban areas. The most prevalent modifiable stroke-risk factors in all areas were hypertension (27.1% rural and 22.4% urban, p = 0.004), overweight and obesity (22.0% rural and 42% urban, p < 0.0001), and elevated waist hip ratio (25.8% rural and 24.1% urban, p = 0.045). Diabetes, smoking, physical inactivity, harmful alcohol consumption were found in ≤5%. Age, family history of hypertension, and waist hip ratio were associated with hypertension in all, while BMI, HIV were associated with hypertension only in urban dwellers. Sex and family history of hypertension were associated with BMI in all, while age, socio-economic status and diabetes were associated with BMI only in urban dwellers. CONCLUSIONS: The prevalence of stroke-risk factors of diabetes, smoking, inactivity and harmful alcohol consumption was rare in Uganda. Rural dwellers belonging to a higher age group tended to be with hypertension and elevated waist hip ratio. Unlike high-income countries, higher socioeconomic status was associated with overweight and obesity.