Accounting for antihypertensive medication in Mendelian randomization studies of blood pressure: methodological considerations in the Canadian Longitudinal Study on Aging.

BACKGROUND: Mendelian randomization (MR) studies investigating determinants of blood pressure (BP) do not account for antihypertensive medication consistently, which may explain discrepancies across studies. We performed an MR study of the association between body mass index (BMI) and systolic BP (SBP) using five methods to account for antihypertensive medication and evaluated their impact on the estimation of the causal effect and on the assessment of the invalidity of the instruments used in MR. METHODS: Baseline and follow-up data on 20 430 participants from the Canadian Longitudinal Study on Aging (CLSA) Comprehensive cohort (2011-2018) were used. The five methods to account for antihypertensive medication in the MR study were: no correction, adjustment for antihypertensive medication as a covariate in models, exclusion of treated individuals, addition of a constant value of 15 mmHg to measured values of SBP in treated individuals, and using hypertension as a binary outcome. RESULTS: The magnitude of the estimated MR causal effect for SBP (mmHg) varied across the methods of accounting for antihypertensive medication effects ranging from 0.68 (effect per 1 kg/m 2 increase in BMI) in scenario adjusting MR models for medication covariate to 1.35 in that adding 15 mmHg to measured SBP in treated individuals. Conversely, the assessment of the validity of the instruments did not differ across methods of accounting for antihypertensive medication. CONCLUSIONS: Methods to account for antihypertensive medication in MR studies may affect the estimation of the causal effects and must be selected with caution.

Mendelian Randomization: A Review of Methods for the Prevention, Assessment, and Discussion of Pleiotropy in Studies Using the Fat Mass and Obesity-Associated Gene as an Instrument for Adiposity.

Pleiotropy assessment is critical for the validity of Mendelian randomization (MR) analyses, and its management remains a challenging task for researchers. This review examines how the authors of MR studies address bias due to pleiotropy in practice. We reviewed Pubmed, Medline, Embase and Web of Science for MR studies published before 21 May 2020 that used at least one single-nucleotide polymorphism (SNP) in the fat mass and obesity-associated (FTO) gene as instrumental variable (IV) for body mass index, irrespective of the outcome. We reviewed: 1) the approaches used to prevent pleiotropy, 2) the methods cited to detect or control the independence or the exclusion restriction assumption highlighting whether pleiotropy assessment was explicitly stated to justify the use of these methods, and 3) the discussion of findings related to pleiotropy. We included 128 studies, of which thirty-three reported one approach to prevent pleiotropy, such as the use of multiple (independent) SNPs combined in a genetic risk score as IVs. One hundred and twenty studies cited at least one method to detect or account for pleiotropy, including robust and other IV estimation methods (n = 70), methods for detection of heterogeneity between estimated causal effects across IVs (n = 72), methods to detect or account associations between IV and outcome outside thought the exposure (n = 85), and other methods (n = 5). Twenty-one studies suspected IV invalidity, of which 16 explicitly referred to pleiotropy, and six incriminating FTO SNPs. Most reviewed MR studies have cited methods to prevent or to detect or control bias due to pleiotropy. These methods are heterogeneous, their triangulation should increase the reliability of causal inference.

Factors associated with residual urine volume preservation in patients undergoing hemodialysis for end-stage kidney disease in Kinshasa.

BACKGROUND: Decreased residual urine volume (RUV) is associated with higher mortality in hemodialysis (HD). However, few studies have examined RUV in patients on HD in Sub-Saharan Africa. The aim of this study was to identify predictors of RUV among incident hemodialysis patients in Kinshasa. METHODS: This historical cohort study enrolled 250 patients with ESRD undergoing hemodialysis between January 2007 and July 2013 in two hemodialysis centers in Kinshasa. RUV were collected over 24 h at the initiation of HD and 6 and 12 months later during the interdialytic period. We compared the baseline characteristics of the patients according to their initial RUV (≤ 500 ml/day vs >  500 ml/day) using Student's t, Mann-Whitney U and Chi2 tests. Linear mixed-effects models were used to search for predictors of decreased RUV by adding potentially predictive baseline covariates of the evolution of RUV to the effect of time: age, sex, diabetes mellitus, hypertension, diastolic blood pressure, diuretics, angiotensin conversion enzyme inhibitors (ACEI), angiotensin receptor blockers, hypovolemia, chronic tubulointerstitial nephropathy, left ventricular hypertrophy and initial hemodialysis characteristic. A value of p < 0.05 was considered the threshold of statistical significance. RESULTS: The majority of hemodialysis patients were male (68.8%, sex ratio 2.2), with a mean age of 52.5 ± 12.3 years. The population's RUV decreased with time, but with a slight deceleration. The mean RUV values were 680 ± 537 ml/day, 558 ± 442 ml/day and 499 ± 475 ml/day, respectively, at the initiation of HD and at 6 and 12 months later. The use of ACEI at the initiation of HD (beta coefficient 219.5, p < 0.001) and the presence of chronic tubulointerstitial nephropathy (beta coefficient 291.8, p = 0.007) were significantly associated with RUV preservation over time. In contrast, the presence of left ventricular hypertrophy at the initiation of HD was significantly associated with decreased RUV over time (beta coefficient - 133.9, p = 0.029). CONCLUSIONS: Among incident hemodialysis patients, the use of ACEI, the presence of chronic tubulointerstitial nephropathy and reduced left ventricular hypertrophy are associated with greater RUV preservation in the first year of dialysis.

Prevalence and Sex-Specific Distribution of Cardiovascular Risk Factors in University Students in an Urban-Rural Environment of the Democratic Republic of the Congo.

A recent qualitative study on health promotion in non-communicable diseases in Sub-Saharan University students suggested sex differences in knowledge and beliefs concerning a healthy lifestyle. However, the extent to which this is reflected in sex-specific distribution of cardiovascular risk factors among Sub-Saharan African students have not been fully evaluated. The objective of this study was to assess the prevalence and the sex-specific distribution of some modifiable cardiovascular risk factors among students at University of Kikwit in the Democratic Republic of the Congo. This cross-sectional descriptive study included 780 students (62.2% men) at the University of Kikwit between January and March of 2016. Data on physical measurements, lifestyle factors, and medical history were collected. The median age (interquartile range) of the students was 23 years (21-25 years). The modifiable cardiovascular risk factors identified were: alcohol consumption (53.1%), overweight (16.4%), general obesity (1.9%), abdominal obesity (10.4%), tobacco consumption (8.1%), hypertension (7.6%) and high pulse pressure (6.4%). Compared to women, men had a higher prevalence of hypertension (9.9 vs. 3.7%; p = 0.002), tobacco consumption (10.7 vs. 3.7%; p = 0.001), and alcohol consumption (58.4 vs. 44.4%; p < 0.001). In contrast, abdominal obesity was more predominant in women than in men (23.1 vs. 2.7%; p < 0.001). This study suggests a sex-specific distribution of several modifiable cardiovascular risk factors in students at the University of Kikwit. Design of sex-specific, student-targeted health promotion programs may be warranted to reduce the prevalence of risk factors and the subsequent burden of cardiovascular diseases.

Validity of simple clinical and biological parameters as screening tool for sickle cell anemia for referral to tertiary center in highly resource constraints.

BACKGROUND: In the Democratic Republic of Congo, the incidence of sickle cell anemia (SCA) is estimated around 40 000 neonates per year. However, it is notoriously difficult to perform conventional electrophoresis in all hospitals and laboratories, especially at peripheral levels and rural area. A panel of multiple clinical and laboratory features that would enhance sickle cell disease were assessed for the detection of the disease in highly resource-scarce settings. METHODS: A prospective study was conducted in Kinshasa. Venous blood samples were drawn from each study participant in order to determine the hematologic parameters, the peripheral smears, and the hemoglobin electrophoresis. We used Cohen's κ statistic to examine the agreement of each variable and diagnosis of sickle cell disease. RESULTS: A total of 807 patients were screened for sickle cell disease. Among these 807 children, 36 (4.5%) were homozygous for Hb S disease. The presence of at least 8% erythroblasts (PPV: 91%, NPV: 99%, sensitivity: 83.3%, specificity: 99.6%, κ value: .86) and sickle cells (PPV:100%, NPV: 98%, sensitivity: 50%, specificity: 100%, κ value: .66) in the peripheral blood smear had an acceptable agreement for sickle cell disease. CONCLUSION: These two biological markers may guide the clinician in the decision-making to initiate the management of the children as a sickle cell patient, pending confirmation of the disease by electrophoresis techniques.