Dyslipidaemia in patients with chronic kidney disease - a neglected cardiovascular risk factor.

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is a major cause of morbidity and mortality in patients with chronic kidney disease (CKD). In addition, CKD itself is a coronary artery disease equivalent due to its atherogenic potential. Despite the role of CKD in ASCVD and recommendations to control lipid levels aggressively, landmark lipid studies have often excluded patients with advanced CKD. Furthermore, there is a scarcity of data on the use and efficacy of lipid-lowering therapy (LLT) in those with CKD in South Africa (SA). OBJECTIVES: To determine the prevalence and control of dyslipidaemia in a cohort of SA patients with CKD. METHODS: A retrospective, cross-sectional observational study of 250 patients with CKD attending the Charlotte Maxeke Johannesburg Academic Hospital renal clinic from 1 July 2019 to 31 July 2020 was carried out. Lipograms, the use of LLT and achievement of target lipid levels were examined. RESULTS: The median (interquartile range) age of this cohort was 58 (46 - 69) years; 50.4% were males and 64.4% black African. Dyslipidaemia was prevalent in 83.6% (n=209) of patients. A total of 169 (67.6%) patients were on LLT, and of these only 28 (16.6%) achieved the recommended low-density lipoprotein cholesterol (LDL-C) target. Of those not on LLT, 51 (63%) were eligible for LLT and almost all were classified as either very high risk (64.2%) or high risk (28.4%) for ASCVD. Of those on LLT, all were on statin therapy, of which simvastatin at a mean dose of 20 mg daily was the most commonly prescribed LLT. CONCLUSION: This cohort comprised a large proportion of patients classified as high or very high risk for ASCVD. Despite this, the use of LLT was inadequate, and <20% of patients were at target LDL-C levels. These data suggest a greater need for awareness of initiating LLT to achieve recommended target LDL-C levels in patients with CKD.

Cerebrotendinous xanthomatosis without neurological involvement.

BACKGROUND: Cerebrotendinous xanthomatosis (CTX) is an autosomal recessively inherited inborn error of metabolism. Neurological symptoms are considered to be a clinical hallmark of untreated adult patients. We describe a 'milder CTX phenotype', without neurological involvement. METHODS: We performed a retrospective patient file study in 79 genetically confirmed Dutch patients with CTX (55 patients aged ≥ 21 years) to study the clinical heterogeneity of CTX. We studied the frequency of adult patients with CTX without neurological involvement at diagnosis, in our Dutch cohort, and included a family from South Africa and patients from Italy, USA, Chile and Asia from the literature. RESULTS: In total, we describe 19 adult patients with CTX from 16 independent families, without neurological symptoms at diagnosis. A relatively small percentage (21%, n = 4) had a history of cataract. The majority, 84% (n = 16), presented with tendon xanthomas as the sole or predominant feature. The majority of patients showed increased plasma cholesterol levels. No correlation was found between this 'milder phenotype', the cholestanol levels and the CYP27A1 genotype. In addition, we describe three novel mutations in the CYP27A1 gene. CONCLUSIONS: This study shows the clinical heterogeneity of CTX, highlighting the existence of a 'milder phenotype', that is without neurological involvement at diagnosis. Adult patients with CTX may present with tendon xanthomas as the sole or predominant feature, mimicking familial hypercholesterolemia. It is important to realize that the absence of neurological symptoms does not rule out the development of future neurological symptoms. As CTX is a treatable disorder, early diagnosis and initiation of treatment when additional clinical signs occur is therefore essential.

Familial hypercholesterolaemia workshop for leveraging point-of-care testing and personalised medicine in association with the Lipid and Atherosclerosis Society of Southern Africa.

Familial hypercholesterolaemia (FH) is a common autosomal dominantly inherited disorder in which impaired clearance of plasma low-density lipoprotein cholesterol causes premature atherosclerotic vascular disease and tendon xanthomata. This workshop aimed to consolidate information on the diagnosis and management of FH in South Africa. The genetic causes include mutations in the LDL receptor, apolipoprotein B100 and proprotein convertase subtilisin/kexin type 9 (PCSK9). Additionally, the concatenation of multiple gene variants can result in polygenic FH. Therapeutic measures include a healthy lifestyle, statins and cholesterol-absorption inhibitors that will achieve control of the dyslipidaemia in the majority of cases. The recently introduced monoclonal antibodies to PCSK9 can improve achievement of target concentration in severe cases. FH is present in all sectors of the South African population but there is sparse documentation in the indigenous African populations. FH should be actively sought, diagnosed and treated with judicious pharmacotherapy and screening of relatives.

South African dyslipidaemia guideline consensus statement: 2018 update A joint statement from the South African Heart Association (SA Heart) and the Lipid and Atherosclerosis Society of Southern Africa (LASSA).

South Africa (SA) is home to a heterogeneous population with a wide range of cardiovascular risk factors. Cholesterol reduction in combination with aggressive management of modifiable risk factors, including nutrition, physical activity, blood pressure and smoking, can help to reduce and prevent morbidity and mortality in individuals who are at increased risk of cardiovascular events. This updated consensus guide to management of dyslipidaemia in SA is based on the updated European Society of Cardiology and European Atherosclerosis Society dyslipidaemia guidelines published in 2016. For individuals who are not considered to be at high or very high cardiovascular risk, the decision whether to treat and which interventional strategy to use is based on a cardiovascular risk score calculated using total cholesterol, high-density lipoprotein cholesterol (HDL-C), gender, age and smoking status. The cardiovascular risk score refers to the 10-year risk of any cardiovascular event and includes 4 categories of risk (low, moderate, high and very high). People with established cardiovascular disease, diabetes mellitus, chronic kidney disease and genetic or severe dyslipidaemias are considered to already be at high or very high risk and do not require risk scoring. Therapeutic lifestyle change is the mainstay of management for all patients. The need for and intensity of drug therapy is determined according to baseline low-density lipoprotein (LDL-C) levels and the target LDL-C concentration appropriate to the individual. LDL-C treatment targets are based on pre-treatment risk and are as follows: <3 mmol/L in low- and moderate risk cases; <2.5 mmol/L and a reduction of at least 50% if the baseline concentration is 2.5 - 5.2 mmol/L in high-risk cases; and <1.8 mmol/L and a reduction of at least 50% if the baseline concentration is 1.8 - 3.5 mmol/L in very high-risk cases. A statin is usually recommended first-line; the specific agent is based on the required degree of cholesterol reduction, comorbidities and co-prescribed medication. Special attention should be paid to children with a family history of genetic or severe dyslipidaemia, who should be screened for dyslipidaemia from 8 years of age. In SA, HIV infection is not considered to be a significant cardiovascular risk factor and treatment recommendations for HIV-positive individuals are the same as for the general population, with careful choice of pharmacotherapy to avoid potential adverse drug-drug interactions. The benefit of statins in individuals older than 70 years is uncertain and clinical judgement should be used to guide treatment decisions and to avoid side-effects and overmedication in this group.

Prevalence and pattern of dyslipidaemia in type 2 diabetes mellitus patients at a tertiary care hospital

Background: Diabetes mellitus (DM) is a common secondary cause of dyslipidaemia, particularly if glycaemic control is poor, which in turn is an important risk factor for atherosclerosis and coronary artery disease.Objectives: (1) To study the prevalence and pattern of dyslipidaemia in patients with type 2 DM. (2) To determine the relationship (if any) between HbA1C and the lipid profile in type 2 diabetic patients.Methods: This was a cross-sectional study done in 200 type 2 diabetic patients attending the Diabetic Clinic at the Helen Joseph Hospital. Patients suffering from other known causes of secondary dyslipidaemia were excluded. Each patient's HbA1C and lipid profile results were recorded from their clinic files. The lipid profile included total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and calculated low-density lipoprotein cholesterol (LDL-C). Patients with one or more of the above parameters outside the targets recommended by the 2012 South African Dyslipidaemia Guidelines were considered to have uncontrolled dyslipidaemia.Results: Of the 200 type 2 DM patients studied, 86 (43%) were male and 114 (57%) female. Despite all patients being treated with lipid-lowering therapy (simvastatin at a mean daily dose of 20 mg), 187 patients (93.5%) did not achieve all their lipid targets. The most prevalent lipid parameter not at target was an LDL-C of ≥ 1.8 mmol/l in nearly 80% of patients. The most common pattern of dyslipidaemia was a combined dyslipidaemia(any two abnormal lipid parameters) affecting a total of 82 out of the 187 patients (43.8%) not reaching recommended targets. No significant relationship was found between HbA1C and any of the lipid parameters. Conclusion: The vast majority of the type 2 diabetic patients studied had dyslipidaemia not meeting recommended targets, despite the use of lipid-lowering therapy in all patients. There is a need for more intensive lipid-lowering therapy, particularly statin therapy in patients with dyslipidaemia. Measures aimed at combating obesity and other lifestyle-related risk factors are also vital and need to be implemented for effectively controlling dyslipidaemia and reducing the burden of CVD

Effects of diabetes mellitus on health-related quality of life at a tertiary hospital in South Africa: A cross-sectional study.

BACKGROUND: Diabetes mellitus (DM) is a chronic metabolic disease that potentially causes debilitating and life-threatening complications, demands a lifestyle change, and has important implications with regard to wellbeing and health-related quality of life (HRQOL). OBJECTIVES: To: (i) determine the HRQOL of a sample of patients with type 2 diabetes; (ii) describe the demographics (age, gender, and smoking and alcohol use) of the population studied; (iii) document the following parameters, which are important in determining the control and severity of type 2 diabetes: (a) glycosylated haemoglobin (HbA1C), (b) total amount of insulin required per day (if on insulin therapy), (c) body mass index (BMI), and (d) exercise compliance; (iv) determine whether there was an association between any or all of the above parameters and the HRQOL of these patients; and (v) determine whether coexisting diseases (hypertension (HT) and dyslipidaemia) were present, and compare HRQOL between diabetic patients with and without these diseases. METHODS: This was a cross-sectional and descriptive study of 200 patients attending the diabetes clinic at Helen Joseph Hospital, Johannesburg, South Africa. HRQOL assessments were made using the Diabetes 39 (D-39) questionnaire, which patients filled in once consent had been obtained and if they fulfilled the inclusion criteria. Patients' questionnaire forms were then analysed with regard to their demographics (age and gender), exercise regimen, smoking and alcohol history, employment status, living arrangements, age of diagnosis of DM, and concurrent use of antihypertensive and cholesterol-lowering drugs. The patients' files were analysed and various clinical parameters were noted (HbA1C, lipogram, BMI, number of insulin units used per day, and whether any antihypertensive and/or lipid-lowering drugs were used). RESULTS: There was an association between HRQOL and HbA1C, and between HRQOL and HT and dyslipidaemia. CONCLUSIONS: No association was found between HRQOL and other clinical parameters, namely number of insulin units used per day, exercise, BMI, lipogram and the use of oral hypoglycaemic agents. Demographic parameters (age, gender, age at diagnosis, employment status and living arrangements) were also shown to have no impact on HRQOL. We found no association between HRQOL in patients who consumed alcohol and smoked cigarettes and in those who did not.

Glycaemic, blood pressure and cholesterol control in 25 629 diabetics.

OBJECTIVE: To examine and compare the extent to which people with type 2 diabetes (T2DM) are achieving haemoglobin A1c (HbA1c), blood pressure (BP) and LDL cholesterol (LDL-C) treatment targets. METHODS: A review of databases (MEDLINE Ovid, Pubmed and Sabinet) was performed and limited to the following terms: type 2 diabetes mellitus AND guideline AND goal achievement for the years 2009 to 2014 (five years). RESULTS: A total of 14 studies (25 629 patients) were selected across 19 different countries. An HbA1c level of 7.0% (or less) was achieved by 44.5% of subjects (range 19.2-70.5%), while 35.2% (range 7.4-66.3%) achieved BP of 130/80 mmHg (or less), and 51.4% (range 20.0-82.9%) had an LDL-C level of either 2.5 or 2.6 mmol/l (100 mg/dl or less). CONCLUSION: Despite guideline recommendations that lowering of HbA1c, BP and lipids to target levels in T2DM will lead to a reduction in morbidity and mortality rates, we found that control of these risk factors remains suboptimal, even across different settings.

Hypercholesterolaemia in Children and Young Adults - Current Management

Atherosclerosis begins in childhood. Not uncommonly; the first presentation of atherosclerosis is sudden cardiac death. It therefore makes sense that risk-factor modification to prevent the development or delay the onset of atherosclerosis needs to begin early in life. Dietary intervention is the key component for the primary prevention of hyperlipidae- mia. However; if diet and lifestyle fail to correct hyperlipidaemia; drug therapy may have to be considered. All children and adolescents with high-risk lipid disorders such as familial hypercholesterolaemia (FH); those with diabetes mellitus or other cardiovascular disease risk factors or with a family history of premature coronary artery disease should be considered for lipid-lowering therapy if diet and lifestyle intervention are ineffective. There are now numerous studies that have documented the safety and efficacy of statin therapy in both children and young adults. Based on these studies; it is now recommended that statin therapy be initiated in all male FH children from the age of ten years and at the onset of menses in females with FH. The initiation of statin therapy could be considered even earlier in FH children at high risk

Sub-Optimal Management of Type 2 Diabetes Mellitus - A Local Audit

Background: Despite increased awareness of risk factors for coronary artery disease and randomized trial data supporting comprehensive diabetic care; these risk factors continue to be largely ignored in patients with type 2 diabetes mellitus. Objective: Cross-sectional study to determine the level of control in patients with type 2 diabetes in tertiary diabetes clinics. Methods: Patient demographic; diabetes and cardiovascular disease related (CVD) data was collected from 150 (F:M; 98:52) randomly selected patients with type 2 diabetes mellitus attending the diabetes clinics at the three academic teaching hospitals served by the University of the Witwatersrand. Blood pressure; height; weight; body mass index and waist circumference were measured. Glycated haemoglobin and fasting serum lipid levels were obtained from patient records. Black patients contributed 68; White 12; 7; Indian 10; 7and Coloured 8; 7. Results: Mean HbA1c for the whole cohort was 8; 7. Obesity was present in 37; 3; hypercholesterolaemia in 29; 3and hypertriglyceridaemia in 45; 3. Waist circumference was = 80 cm in 98of the females and = 94 cm in 69of the males. 127 patients out of 150 (85) were hypertensive and 74of these had a systolic blood pressure = 130 mmHg and 84a diastolic blood pressure = 80 mmHg. 43of the patients did minimal exercise; 6smoked and only 51were on aspirin. Conclusion: Comprehensive diabetic care is still largely lacking despite clinical trial data documenting improved outcomes associated not only with glycaemic control but also with use of antihypertensive; lipid lowering and anti-platelet therapy

Shift work and its effects on the cardiovascular system.

The practice of shift-work scheduling has long been part of normal work duties in emergency services such as health and security. It is only recently, in the wake of growing job opportunities and booming industries, where more employees are needed to keep services running over 24-hour periods that studies on the effects of shift work on workers' health have begun to delve deeper. The desynchronisation that occurs in circadian rhythms, with respect to sleep cycles, predisposes employees to coronary heart disease, gastrointestinal disturbances, increased risk of breast cancer and poor pregnancy outcomes. This literature review focuses on circadian rhythms, their molecular components, disturbances of these rhythms as a result of shift work and the adverse effects thereof on the cardiovascular system.

The evaluation of low-density lipoprotein cholesterol goals achieved in patients with established cardiovascular disease and/or hyperlipidaemia receiving lipid-lowering therapy: the South African Not at Goal study (SA-NAG).

AIM: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Dyslipidaemia is a major risk factor that leads to the clinical sequelae of CVD. As a result, it has become essential for South Africa to update its guidelines for the management of dyslipidaemia, and the South African scientific community has recently adopted the European guidelines on CVD prevention in clinical practice. The South African Not at Goal study (SA-NAG) was a survey done to determine the percentage of patients on lipid-lowering therapy who were not achieving guideline-specified low-density lipoprotein cholesterol (LDL-C) goals. METHODS: In this cross-sectional study, dyslipidaemic and/or CVD patients on lipid-lowering therapy for more than four months were enrolled. V olunteers had their demographic data and previous medical history documented. Blood samples from these patients were analysed (using standardised methods) to obtain fasting blood lipid and glucose levels. RESULTS: In total, 1,201 patients (age 58 +/- 11.4 years) were recruited by physicians and general practitioners from across South Africa. Under the new guidelines, 41% of patients were defined as low risk (LR) and 59% were high risk (HR). Sixty-three per cent of LR patients and 77% of HR patients (71% overall) did not achieve their LDL-C target goals of 2.5 and 3.0 mmol/l, respectively. The LR and HR patients who did not achieve their LDL-C goals were on average 19% (0.7 mmol/l +/- 0.5) and 31% (1.1 mmol/l +/- 1.1) above their LDL-C target levels, respectively. CONCLUSIONS: These results suggest that a considerable number of patients fall into the category 'not at goal' LDL-C. Patients who failed to achieve goal were also far above their LDL-C target levels. The adoption of the new guidelines will necessitate enhanced disease management to reduce the disease burden.