Association of body mass index with left ventricular diastolic dysfunction among ambulatory individuals with diabetes mellitus in rural Uganda: a cross-sectional study.

BACKGROUND: Left ventricular diastolic dysfunction (LVDD) is a recognized complication of diabetes mellitus that precedes and is a risk factor for heart failure. We aimed to determine the prevalence of LVDD and its association with body mass index in ambulatory adults with diabetes mellitus in rural Uganda. METHODS: We conducted a cross-sectional study, over 5 months, to enroll 195 ambulatory Ugandan adults living with diabetes mellitus for at least five years at Mbarara Regional Referral Hospital. We collected demographic, and clinical data and measured body mass index (BMI). Echocardiography was performed to determine LVDD by assessing the mitral inflow ventricular filling velocities (E/A and E/è ratios), tricuspid regurgitant jet peak velocity, and left atrium maximum volume index. We used logistic regression to estimate the odds ratio for the association of LVDD with BMI and evaluated the variation of associations by age and hypertension status. RESULTS: Of the 195 participants, 141 (72.31%) were female, the mean age was 62 [standard deviation, 11.50] years, and the median duration of diabetes diagnosis was 10 [interquartile range, 7, 15] years. Eighty-six percent (n = 168) had LVDD with the majority (n = 127, 65.1%) of participants in the grade 1 category of LVDD. In the adjusted model, the odds of LVDD for each 1 kg/m2 increase in BMI was 1.11 [95% confidence interval 1.00, 1.25, p = 0.04]. The adjusted odds of LVDD among individuals aged ≥ 50 years with BMI ≥ 25 kg/m2 was 13.82 times the odds of LVDD in individuals aged < 50 years with BMI < 25 kg/m2. CONCLUSION: LVDD is prevalent and positively associated with BMI among ambulatory Ugandan adults living with diabetes mellitus for at least five years. The association was higher for older overweight/obese than younger individuals with normal weight. Future studies should focus on the effect of weight loss on LVDD as a possible target for the prevention of heart failure.

Rheumatic heart disease in Uganda: the association between MHC class II HLA DR alleles and disease: a case control study.

BACKGROUND: Rheumatic heart disease (RHD), the only long term consequence of acute rheumatic fever, remains a leading cause of morbidity and mortality among young adults in Uganda. An inherited susceptibility to acute rheumatic fever centers around the major histocompatibility class II human leucocyte antigens. However, there is paucity of data from sub-Saharan Africa. This study compares the frequency of HLA class II DR alleles between RHD cases and normal controls in Uganda. METHODS: One hundred ninety-nine participants including 96 established RHD cases aged 5-60 years and 103 age and sex matched normal controls were recruited for participation. DNA was manually extracted from buffy coat samples and HLA analysis was performed. HLA-DR allelic frequency comparison between cases and controls were estimated using conditional logistic regression with 95% confidence intervals. P -values were corrected for multiple hypothesis testing. RESULTS: 199 participants (103 female, 51.8%) completed the study. The mean (SD) age in years for cases and controls were 29.6 (10.2) and 29(18), respectively. After conditional logistic regression and multiple hypothesis testing, HLA-DR1was associated with a decreased risk of RHD (OR = 0.42, CI 0.21-085, P = 0.01, Corrected P value (PC) = 0.09,) while HLA-DR11 was associated with increased risk of RHD (OR = 3.31, CI 1.57-6.97, P = <0.001, Pc < 0.001). No other significant associations were found. CONCLUSION: In this first study of HLA genetic susceptibility to RHD in Uganda, HLA- DR1 was more common in normal controls while HLA- DR11 was more common among RHD cases suggesting a disease susceptibility association. In future studies, high resolution HLA analysis and genome wide studies should be carried out to confirm this pattern.

Proportion of patients in the Uganda rheumatic heart disease registry with advanced disease requiring urgent surgical interventions.

INTRODUCTION: Since the establishment of the Uganda Rheumatic Heart Registry, over 900 patients have been enrolled. We sought to stratify the patients in the registry according to disease severity and optimal management strategy. METHODS: We reviewed data of 618 patients who had enrolled in the Registry between March 2010 and February 2013. The 67 patients who had died were excluded leaving 551 patients who were recruited. The optimum management strategy was determined according to the 2012 European Society of Cardiology guidelines on the management of valvular heart disease. RESULTS: Out of the 551 patient's records evaluated, 398 (72.3%) required invasive intervention, with 332(60.3%) patients requiring surgery and 66 (12.0%) requiring percutaneous mitral commissurotomy (PMC). This leaves only 27.7% of patients who required only medical management. Currently, majority of the patients (498, 90.4%) in the registry are on medical treatment. Of the 60.3% requiring surgical intervention, only 8.0% (44 patients) underwent valvular surgery and 5(1.0%) patients of the 66 (12.0%) underwent PMC successfully. CONCLUSION: There is a high proportion of patients with severe disease that require surgical treatment yet they cannot access this therapy due to absence of local expertise.

Towards reframing health service delivery in Uganda: the Uganda Initiative for Integrated Management of Non-Communicable Diseases.

BACKGROUND: The burden of non-communicable diseases (NCDs) in low- and middle-income countries (LMICs) is accelerating. Given that the capacity of health systems in LMICs is already strained by the weight of communicable diseases, these countries find themselves facing a double burden of disease. NCDs contribute significantly to morbidity and mortality, thereby playing a major role in the cycle of poverty, and impeding development. METHODS: Integrated approaches to health service delivery and healthcare worker (HCW) training will be necessary in order to successfully combat the great challenge posed by NCDs. RESULTS: In 2013, we formed the Uganda Initiative for Integrated Management of NCDs (UINCD), a multidisciplinary research collaboration that aims to present a systems approach to integrated management of chronic disease prevention, care, and the training of HCWs. DISCUSSION: Through broad-based stakeholder engagement, catalytic partnerships, and a collective vision, UINCD is working to reframe integrated health service delivery in Uganda.

Cardiovascular complications in newly diagnosed rheumatic heart disease patients at Mulago Hospital, Uganda.

BACKGROUND: Complications of rheumatic heart disease are associated with severe morbidity and mortality in developing countries where the disease prevalence remains high. Due to lack of screening services, many patients present late, with severe valve disease. In Uganda, the disease and its complications are still not well studied. OBJECTIVE: To profile and describe cardiovascular complications in newly diagnosed rheumatic heart disease patients attending the Mulago National Referral Hospital in Uganda. METHODS: This was a cross-sectional study where consecutive, newly diagnosed rheumatic heart disease patients were assessed and followed up for complications, such as heart failure, pulmonary hypertension, atrial fibrillation, recurrence of acute rheumatic fever, and stroke. RESULTS: A total of 309 (115 males and 196 females) definite rheumatic heart disease patients aged 15-60 years were enrolled in the study and analysed. Complications occurred in 49% (152/309) of the newly diagnosed rheumatic heart disease cases, with heart failure (46.9%) the most common complication, followed by pulmonary arterial hypertension (32.7%), atrial fibrillation (13.9%), recurrence of acute rheumatic fever (11.4%), infective endocarditis (4.5%) and stroke (1.3%). Atrial fibrillation and acute rheumatic fever were the most common complications associated with heart failure. CONCLUSION: In this study we found that about 50% of newly diagnosed rheumatic heart disease patients in Uganda presented with complications. Heart failure and pulmonary arterial hypertension were the most commonly observed complications.

Socioeconomic and environmental risk factors among rheumatic heart disease patients in Uganda.

BACKGROUND: Although low socioeconomic status, and environmental factors are known risk factors for rheumatic heart disease in other societies, risk factors for rheumatic heart disease remain less well described in Uganda. AIMS AND OBJECTIVE: The objective of this study was to investigate the role of socio-economic and environmental factors in the pathogenesis of rheumatic heart disease in Ugandan patients. METHODS: This was a case control study in which rheumatic heart disease cases and normal controls aged 5-60 years were recruited and investigated for socioeconomic and environmental risk factors such as income status, employment status, distance from the nearest health centre, number of people per house and space area per person. RESULTS: 486 participants (243 cases and 243 controls) took part in the study. Average age was 32.37+/-14.6 years for cases and 35.75+/-12.6 years for controls. At univariate level, Cases tended to be more overcrowded than controls; 8.0+/-3.0 versus 6.0+/-3.0 persons per house. Controls were better spaced at 25.2 square feet versus 16.9 for cases. More controls than cases were employed; 45.3% versus 21.1%. Controls lived closer to health centers than the cases; 4.8+/-3.8 versus 3.3+/-12.9 kilometers. At multivariate level, the odds of rheumatic heart disease was 1.7 times higher for unemployment status (OR = 1.7, 95% CI = 1.05-8.19) and 1.3 times higher for overcrowding (OR = 1.35, 95% CI = 1.1-1.56). There was interaction between overcrowding and longer distance from the nearest health centre (OR = 1.20, 95% CI = 1.05-1.42). CONCLUSION: The major findings of this study were that there was a trend towards increased risk of rheumatic heart disease in association with overcrowding and unemployment. There was interaction between overcrowding and distance from the nearest health center, suggesting that the effect of overcrowding on the risk of acquiring rheumatic heart disease increases with every kilometer increase from the nearest health center.

Anti-oxidant effects of atorvastatin in dexamethasone-induced hypertension in the rat.

1. Dexamethasone (Dex)-induced hypertension is characterized by endothelial dysfunction associated with nitric oxide (NO) deficiency and increased superoxide (O2-) production. Atorvastatin (Ato) possesses pleiotropic properties that have been reported to improve endothelial function through increased availability of NO and reduced O2- production in various forms of hypertension. In the present study, we investigated whether 50 mg/kg per day, p.o., Ato could prevent endothelial NO synthase (eNOS) downregulation and the increase in O2- in Sprague-Dawley (SD) rats, thereby reducing blood pressure. 2. Male SD rats (n = 30) were treated with Ato (50 mg/kg per day in drinking water) or tap water for 15 days. Dexamethasone (10 microg/kg per day, s.c.) or saline was started after 4 days in Ato-treated and non-treated rats and continued for 11-13 days. Systolic blood pressure (SBP) was measured on alternate days using the tail-cuff method. Endothelial function was assessed by acetylcholine-induced vasorelaxation and phenylephrine-induced vasoconstriction in aortic segments. Vascular eNOS mRNA was assessed by semi-quantitative reverse transcription-polymerase chain reaction. 3. In rats treated with Dex alone, SBP was increased from 109 +/- 2 to 133 +/- 2 mmHg on Days 4 and Day 14, respectively (P < 0.001). In the Ato + Dex group, SBP was increased from 113 +/- 2 to 119 +/- 2 mmHg on Days 4 to 14, respectively (P < 0.001), but was significantly lower than SBP in the group treated with Dex alone (P < 0.05). Endothelial-dependent relaxation and eNOS mRNA expression were greater in the Dex + Ato group than in the Dex only group (P < 0.05 and P < 0.0001, respectively). Aortic superoxide production was lower in the Dex + Ato group compared with the group treated with Dex alone (P < 0.0001). 4. Treatment with Ato improved endothelial function, reduced superoxide production and reduced SBP in Dex-treated SD rats.

Atorvastatin prevented and partially reversed adrenocorticotropic hormone-induced hypertension in the rat.

1. Adrenocorticotropic hormone (ACTH)-induced hypertension is associated with nitric oxide (NO) deficiency and increased oxidative stress. Atorvastatin (Ato), an HMG-Co-enzyme-A reductase inhibitor has been reported to enhance availability of NO. The aim of the study was to assess whether pretreatment with Ato would prevent the development of ACTH-induced hypertension and whether established ACTH-induced hypertension could be reversed with subsequent administration of Ato in rats. 2. Male Sprague-Dawley rats (n = 60) were treated with Ato (30 mg/kg per day in drinking water) or tap water for 15 days. ACTH (0.2 mg/kg per day s.c) or saline was started 4 days after Ato treatment or non-treated rats and continued for 11-13 days (prevention study). In the reversal study, Ato was given on day 8 of ACTH/Saline treatment for 5 days. Systolic blood pressure (SBP) was measured on alternate days using the tail cuff method. 3. Adrenocorticotropic hormone treatment increased SBP (110 +/- 2-136 +/- 2 mmHg, P < 0.001) and aortic superoxide production (P < 0.001). Ato alone did not alter SBP, but Ato pretreatment prevented ACTH-induced hypertension compared with that in rats treated with ACTH alone (118 +/- 2 and 136 +/- 2 mmHg, respectively, P cent < 0.01). Ato partially reversed ACTH-induced hypertension (124 +/- 3 and 136 +/- 2 mmHg, respectively, P cent < 0.05). Plasma nitrate/nitrite (NOx) was decreased in ACTH-treated rats compared with saline treated rats (6.6 +/- 0.4 saline and 4.5 +/- 0.5 micromol/L ACTH, P < 0.001). Atorvastatin affected neither plasma NOx nor aortic superoxide production. 4. Atorvastatin prevented and partially reversed ACTH-induced hypertension in the rat.

N-acetylcysteine antagonizes the development but does not reverse ACTH-induced hypertension in the rat.

We investigated the effect of antioxidant N-acetylcysteine (NAC) on adrenocorticotropic hormone (ACTH)-hypertension. Male Sprague-Dawley rats received NAC (10 mg/L) or water 4 days before ACTH/saline treatment for 13 days (prevention study). In a reversal study, NAC commenced on day 8 of ACTH/saline treatment and continued for 5 days. ACTH increased systolic blood pressure (SBP) in water drinking rats (111 +/- 1 to 131 +/- 3 mmHg, p < 0.001). In the prevention study, NAC + ACTH increased SBP (108 +/- 2 to 120 +/- 2 mmHg, p < 0.001) but less than ACTH alone (p' < 0.05). In the reversal study, NAC had no significant effect (132 +/- 4 to 124 +/- 3 mmHg, ns). Thus, NAC partially prevented but did not reverse ACTH-induced hypertension.