Browsing by Author "Blom, Dirk"

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    A descriptive study of the type 2 diabetic population with hypertriglyceridemia of more than 2.5 mmol/l at presentation with subsequent analysis of their baseline and follow up variables
    (2023) Vermooten, Barbara; Blom, Dirk
    Background Type 2 diabetes mellitus and the dyslipidaemia that often accompanies it are major risk factors for atherosclerotic cardiovascular disease. Elevated triglycerides mark the accumulation of atherogenic remnant lipoproteins. Because there is little South African data on hypertriglyceridaemia in diabetes we retrospectively reviewed baseline and follow-up data of patients attending a specialized lipid clinic. Aim of the study The primary aim of this study is to describe biochemical and demographic variations of a diabetic population with hypertriglyceridemia and to further investigate whether there are correlations between glycemic control, lipid modifying therapy and hypoglycemic therapy with lipid outcomes, specifically LDL cholesterol, remnant cholesterol, triglycerides, and HDL-C. Methods We reviewed the medical records of 100 diabetic patients with hypertriglyceridemia of >2.5mmol/L who attended the Groote Schuur Hospital Lipid clinic for at least two years. The patients were randomly selected from the Lipidology database, and selection was made based on inclusion criteria for this study. We documented four six-monthly follow-up visits and documented the visit with the lowest recorded triglyceride levels if it was outside the two-year follow-up. Results The study population was predominantly (63%) female with a mean (SD) age at presentation of 50.87 (10.44) years. Obesity (BMI >30 kg/m²) was highly prevalent (66.3%) and diabetes was generally poorly controlled (76.16% patients had a HbA1C >7%). Baseline triglycerides ranged from 2.6mmol/L to 63.3mmol/L with a median and mean (SD) of 4.64 mmol/L and 10.47 (12.57) mmol/L, respectively. Baseline agarose electrophoresis patterns were: 0% type I, 0% type IIA, 51.4% type IIB, 10.3% type III, 18.7% type IV and 19.6% type V. LDL particle size determined by acrylamide gradient gel electrophoresis was intermediate or small in 61 of 64 (95%%) of patients with visible LDL. At baseline calculated mean (SD) remnant cholesterol (48 patients) was 1.55 (0.24) mmol/L, ranging from 1.1mmol/L to 2mmol/L. Triglycerides and calculated remnant cholesterol were strongly correlated (r2=0.9395, p=0.000). There was no correlation between baseline TG and HDL-C, baseline BMI and baseline waist circumference (waist/hip ratio could have possibly corrected for different anthropometry), but there was a positive correlation between triglycerides and alcohol intake, (r2=0.224, P=0.012). There was no correlation between baseline triglycerides and HbA1C (p=0.8423) or fasting glucose (p=0.0857). The change in total triglycerides from initial presentation to the follow-up visit with the lowest documented value was a mean (SD) decrease of 2.91 (4.98) mmol/L, ranging from either no change to a decrease of 32.68mmol/L. The mean (SD) reduction in HbA1C was 0.94 (1.64) % ranging from an increase of 1.7% to a decrease of 7.8%. Fibrates were initiated in 43% of patients. Patients prescribed fibrates had higher mean (SD) baseline TG levels of 18.56(15.48) mmol/L, compared to levels of 4.11(1.85) mmol/L in patients who were not prescribed a fibrate. At baseline mean (SD) TC values were 8.33 (3.18). The mean (SD) LDLC at baseline was 4.26 (1.45) mmol/L ranging from 0.5 to 7.6 mmol/L. Only 4.1% of all patients with a calculable LDL-C achieved values below 1.8mmol/L during follow-up. Conclusions In this study diabetic patients with elevated triglycerides who attended a specialist lipid clinic were frequently obese and often had poorly controlled diabetes. Although dyslipidaemia and glycaemia improved following intensification of therapy most patients did not reach their treatment goals. Our study highlights the heterogeneity of hypertriglyceridaemia, the difficulties of achieving good metabolic control, and the need for ongoing follow-up as severe hypertriglyceridaemia relapses readily.
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    Anti-retroviral therapy increases the prevalence of dyslipidemia in South African HIV-infected patients
    (Public Library of Science, 2016) Dave, Joel A; Levitt, Naomi S; Ross, Ian L; Lacerda, Miguel; Maartens, Gary; Blom, Dirk
    Purpose Data on the prevalence of dyslipidaemia and associated risk factors in HIV-infected patients from sub-Saharan Africa is sparse. We performed a cross-sectional analysis in a cohort of HIV-infected South African adults. METHODS: We studied HIV-infected patients who were either antiretroviral therapy (ART)-naive or receiving non-nucleoside reverse transcriptase inhibitor (NNRTI)-based or protease inhibitor (PI)-based ART. Evaluation included fasting lipograms, oral glucose tolerance tests and clinical anthropometry. Dyslipidemia was defined using the NCEP ATPIII guidelines. RESULTS: The median age of the participants was 34 years (range 19-68 years) and 78% were women. The prevalence of dyslipidemia in 406 ART-naive and 551 participants on ART was 90.0% and 85%, respectively. Low HDL-cholesterol (HDLC) was the most common abnormality [290/406 (71%) ART-naïve and 237/551 (43%) ART- participants]. Participants on ART had higher triglycerides (TG), total cholesterol (TC), LDL-cholesterol (LDLC) and HDLC than the ART-naïve group. Severe dyslipidaemia, (LDLC> 4.9 mmol/L or TG >5.0 mmol/L) was present in <5% of participants. In multivariate analyses there were complex associations between age, gender, type and duration of ART and body composition and LDLC, HDLC and TG, which differed between ART-naïve and ART-participants. CONCLUSION: Participants on ART had higher TG, TC, LDLC and HDLC than those who were ART-naïve but severe lipid abnormalities requiring evaluation and treatment were uncommon.
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    Efficacy and safety of alirocumab, a fully human PCSK9 monoclonal antibody, in high cardiovascular risk patients with poorly controlled hypercholesterolemia on maximally tolerated doses of statins: rationale and design of the ODYSSEY COMBO I and II trials
    (2014-09-20) Colhoun, Helen M; Robinson, Jennifer G; Farnier, Michel; Cariou, Bertrand; Blom, Dirk; Kereiakes, Dean J; Lorenzato, Christelle; Pordy, Robert; Chaudhari, Umesh
    Abstract Background Alirocumab is a fully human monoclonal antibody to proprotein convertase subtilisin kexin type 9 (PCSK9) under investigation for treatment of hypercholesterolemia and reduction of cardiovascular events. Methods/design The COMBO studies, part of the Phase 3 ODYSSEY clinical trial program, are designed to evaluate the efficacy and safety of alirocumab as add-on therapy to stable, maximally tolerated daily statin, with or without other lipid-lowering therapy (LLT), in a planned 966 patients with hypercholesterolemia at high cardiovascular risk. COMBO I ( http://clinicaltrials.gov/show/NCT01644175 ) is placebo-controlled, with a double-blind treatment period of 52 weeks, and 306 planned patients who may receive other LLTs in addition to statin therapy. COMBO II ( http://clinicaltrials.gov/show/NCT01644188 ) has a double-blind treatment period of 104 weeks, comparing alirocumab with ezetimibe in 660 planned patients receiving statin therapy (but no other LLTs). The primary efficacy endpoint is the difference between treatment arms in percent change in low-density lipoprotein cholesterol (LDL-C) from baseline to week 24. Both studies utilized a starting dose of alirocumab 75 mg every 2 weeks (Q2W; administered as 1 mL solution via auto-injector). Patients with LDL-C levels ≥70 mg/dL after 8 weeks of treatment were up-titrated in a blinded manner at week 12 to alirocumab 150 mg Q2W (also 1 mL auto-injector). Discussion In conclusion, the COMBO studies will provide information on the long-term efficacy and safety of alirocumab in high-risk patients when administered in addition to maximally tolerated statin therapy, with a flexible dosing strategy which allows for individualized therapy based on the degree of LDL-C lowering needed to achieve the desired treatment response. Trial registrations COMBO I: NCT01644175 ( NCT01644175 ). COMBO II: NCT01644188 ( NCT01644188 ).
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    Towards Evidence-Based Implementation of Pharmacogenomics in Southern Africa: Comorbidities and Polypharmacy Profiles across Diseases
    (Multidisciplinary Digital Publishing Institute, 2023-07-26) Soko, Nyarai Desiree; Muyambo, Sarudzai; Dandara, Michelle T. L.; Kampira, Elizabeth; Blom, Dirk; Jones, Erika S. W.; Rayner, Brian; Shamley, Delva; Sinxadi, Phumla; Dandara, Collet
    Pharmacogenomics may improve patient care by guiding drug selection and dosing; however, this requires prior knowledge of the pharmacogenomics of drugs commonly used in a specific setting. The aim of this study was to identify a preliminary set of pharmacogenetic variants important in Southern Africa. We describe comorbidities in 3997 patients from Malawi, South Africa, and Zimbabwe. These patient cohorts were included in pharmacogenomic studies of anticoagulation, dyslipidemia, hypertension, HIV and breast cancer. The 20 topmost prescribed drugs in this population were identified. Using the literature, a list of pharmacogenes vital in the response to the top 20 drugs was constructed leading to drug–gene pairs potentially informative in translation of pharmacogenomics. The most reported morbidity was hypertension (58.4%), making antihypertensives the most prescribed drugs, particularly amlodipine. Dyslipidemia occurred in 31.5% of the participants, and statins were the most frequently prescribed as cholesterol-lowering drugs. HIV was reported in 20.3% of the study participants, with lamivudine/stavudine/efavirenz being the most prescribed antiretroviral combination. Based on these data, pharmacogenes of immediate interest in Southern African populations include ABCB1, CYP2B6, CYP2C9, CYP2C19, CYP2D6 CYP3A4, CYP3A5, SLC22A1, SLCO1B1 and UGT1A1. Variants in these genes are a good starting point for pharmacogenomic translation programs in Southern Africa.
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    Very low HDL cholesterol: The GSH Experience
    (2022) Ngarivume, Kurai; Blom, Dirk
    Background In epidemiological studies low HDL-C is associated with increased cardiovascular risk. In exceptional cases, e.g., patients with Apo A1 Milano, low levels of HDL-C are cardioprotective. Very little is known about the characteristics of South African patients with very low HDL-C. A detailed description of such a group will identify and characterize a cohort of patients for further study and help to identify clinical factors commonly associated with very low HDL-C in South Africa. Methods We retrospectively collected data on patients with HDL-C < 0.6 mmol/L attending a specialist lipid clinic at Groote Schuur Hospital (GSH) in Cape Town, South Africa. Eligible patients were identified by searching the GSH Lipid Clinic database and data was abstracted from their folders and entered into a Redcap database. Results One hundred and twenty eight (128) patient records were evaluated. The study cohort was predominantly male (60%). The mean (SD) age at presentation was 44.6(11.4) years with males and females presenting at similar ages (p=0.474). Most patients were white followed by mixed ancestry and black African patients. The mean (SD) total cholesterol for the cohort was 8.47(5.13) mmol/L. The mean (SD) HDL-C was 0.53(0.10) mmol/L, while the mean (SD) LDL-C was 4.86(2.10) mmol/L. The median (IQR) triglycerides was 6.05(3.1 – 11.50) mmol/L. Baseline lipid profile showed that very low HDL-C was associated with elevated total cholesterol and hypertriglyceridemia in many patients. 8.59% of the cohort had very low HDL-C levels with normal levels of triglycerides. On follow-up, the best HDL-C ranged from 0.5 – 1.8mmol/L, while the worst recorded HDL-C ranged from 0.2-1.0mmol/L. There was no relationship between age of presentation and level of HDL-C. Hypertension was highly prevalent (39.74% of males and 42% of females). Diabetes was also highly prevalent (41.02% of males and 30.0% of females). At presentation 19.23% males reported a previous cardiovascular complication such as stroke or myocardial infarction compared to 10.00% of the females. Participants that had “Never Smoked” had the lowest HDL-C levels. There was no statistically significant difference in levels of HDL-C at presentation in the patients who were consuming alcohol compared to those who were not consuming alcohol (p=0.7406) Conclusion This study has provided important insights into the characteristics of patients with very low HDL-C in Cape Town South Africa. As expected, it confirms the relationship between low HDLC and the metabolic syndrome as well as the use of medications known to lower HDL-C (beta blockers). The inverse correlation between high triglycerides and low HDL-C was also demonstrated. Unexpected was that HDL-C was not found to correlate with smoking (which tends to lower HDL-C) or alcohol use (which tends to raise HDL-C). Early initiation of lipidmodifying therapy should be encouraged given the high prevalence of other cardiovascular risk factors, or established atherosclerotic cardiovascular disease, in these patients. Patients with very low HDL-C, but without hypertriglyceridaemia would be a worthwhile cohort to study to characterize genetic determinant of very low HDL-C in South Africa.