Anjly Jain

Point of care testing is appropriate for National Health Service health check

Background The Department of Health launched a cardiovascular disease risk assessment initiative with particular reference to reducing health inequalities in ethnic minorities. Collaboration between HEART UK, Royal Free Hampstead NHS Trust and Hindu Temples resulted in vascular screening in North London. Methods Subjects of South Asian origin were screened. A full lipid profile and glucose were measured using a point of care testing (POCT) Cholestech LDX analyser (LDX). Venous samples were analysed in our hospital laboratory. Results The results (215 men; 191 women) were divided into tertiles and Bland–Altman plots were used to assess agreement. At high-density lipoprotein cholesterol (HDL-C) concentrations <1.0 mmol/L the LDX underestimated values by −0.2 mmol/L (P<0.0001). At HDL-C concentrations >1.3 mmol/L this bias disappeared. For total cholesterol the concentration-dependent negative bias was evident at concentrations of <4.1 mmol/L (P < 0.0001). This bias was less evident at higher concentrations. A similar pattern was seen for low-density lipoprotein cholesterol. There were also small variations in glucose and triglyceride values. However, there was excellent agreement in calculated cardiovascular disease risk using kappa analysis for JBS2, QRISK2, ETHRISK and Framingham (κ = 0.86, 0.92, 0.94 and 0.88, respectively). This was a high-risk population since 9.7–19.4% had a ≥20% 10-y probability of a vascular event depending on the risk engine and assay method used. The corresponding values for intermediate risk (11–19%) were 18.6–25.7%. Conclusions There was a minimum mismatch irrespective of the type of risk calculator used. POCT measurements are adequate for the National Health Service Health Check.

South Asians: why are they at a higher risk for cardiovascular disease?

Purpose of review We comment on the high prevalence of cardiovascular disease (CVD) in South Asians (SA). The effect of various risk factors, for example biochemical, genetic, lifestyle, socioeconomic factors and psychosocial stress on CVD risk is discussed. Recent findings ‘Prediabetes’ is common in SA, but its relationship with coronary artery disease (CAD) is not significant unlike for the white population. At the same time, ‘prediabetes’ in SA is associated with an increased risk for cerebrovascular disease (CeVD). The differentiating factor could be the high lipids in Europeans and their relationship to CAD. Likewise, higher diastolic blood pressure in SA may explain the risk of CeVD. Small, dense, low-density lipoprotein (LDL), low high-density lipoprotein-cholesterol (HDL-C) concentration and high triglycerides may contribute to atherosclerosis. Thrombotic factors such as increased levels of plasminogen activator inhibitor, fibrinogen, lipoprotein (a) and homocysteine have been shown to be associated with increased CVD. Impaired cerebrovascular autoregulation and sympathovagal activity, increased arterial stiffness and endothelial dysfunction may increase CVD risk further. In addition, environmental and dietary factors may exaggerate the unfavourable cardiovascular profile through genetic factors. Summary The implications of the findings suggest comprehensive screening of SA for CVD. Cultural differences should be considered while designing prevention strategies specifically targeting barriers for uptake of preventive service.

Lipid Association of India (LAI) expert consensus statement on management of dyslipidaemia in Indians 2017: part 2

ABSTRACT These Lipid Association of India (LAI) recommendations refer to specific patient populations. They follow the previously published LAI part 1 recommendations. These part 2 LAI recommendations focus on specific patient groups. These include patients with heart failure, chronic kidney disease, non-alcoholic fatty liver disease, cerebrovascular disease, thyroid disorders, inflammatory joint diseases, familial hypercholesterolaemia and human immunodeficiency virus infection. We also consider women, the elderly and post-transplantation patients. The current recommendations are based, as much as possible, on available data from Indian populations.

High prevalence of non-alcoholic fatty liver disease (NAFLD) among Gujarati Indians in North London: a population-based study

ABSTRACT Background: The prevalence of non-alcoholic fatty liver disease (NAFLD) among Indian Asians in high-income countries is not well studied, but appears to be different from that for Western populations. Design: Cross-sectional study of subjects recruited through a community cardiovascular (CV) screening programme at two London Hindu temples from 2010–2012. NAFLD was diagnosed using the fatty liver index (FLI) and fibrosis stage through the BARD (Body Mass Index (BMI), Aspartate aminotransferase to Alanine aminotransferase ratio and Diabetes Mellitus) score. Results: 597 subjects were assessed; 306 (51%) female. Median (interquartile range) age and BMI were 49 (40.6–55.0) years and 26.4 (23.5–29.2) kg/m2, respectively. NAFLD was diagnosed in 184 (30.8%) cases, but 175 (29.3%) subjects could not be categorised. Overall, 117 (40.2%) men and 67 (21.9%) women had evidence of NAFLD (p < 0.001). In those with evidence of NAFLD, 142 (78.5%) had a BARD score suggestive of advanced fibrosis. Advanced fibrosis could be excluded in 5 (7.6%) women and 34 (29.6%) men (p < 0.001). Total cholesterol (TC), triglycerides (TG) and non-HDL (high-density lipoprotein cholesterol) were higher in the NAFLD group (p < 0.001), whereas HDL-C was lower (p < 0.001). Conclusion: There is evidence of a high prevalence of asymptomatic NAFLD, possibly in combination with advanced liver damage, among UK-based Gujarati Indians living in London. NAFLD is emerging as an independent risk factor for CV disease. Screening programmes should be developed in order to decrease liver and CV mortality and morbidity in these high-risk patients.

Evaluation of the point of care Afinion AS100 analyser in a community setting

Background A ‘one stop shop’ model for multifactorial risk factor management in a culturally sensitive environment may improve cardiovascular disease and diabetes prevention. A full biochemical profile for cardiovascular disease risk assessment includes a lipid profile, glucose, glycated haemoglobin and urine albumin creatinine ratio measurements. This may require the use of more than one point of care testing instrument. Methods Individuals who attended a community cardiovascular disease risk screening or an audit programme of the diabetic care pathway in the community were sampled. Bland–Altman and Deming regression plots were used to assess agreement between methods for total cholesterol, high-density lipoprotein cholesterol, triglycerides, glycated haemoglobin and urine albumin creatinine ratio. Results There was good agreement between the Afinion AS100 analyser, Cholestech LDX and the laboratory methods for total cholesterol, high-density lipoprotein cholesterol and triglycerides (n = 232). The Afinion AS100 agreed well with the laboratory method for glycated haemoglobin (n = 255) and urine albumin creatinine ratio (n = 176). There was statistically significant bias (p = 0.03 to <0.0001) for several measurements. However, these were judged not to be clinically relevant. Specifically for the total cholesterol and high-density lipoprotein cholesterol values, we obtained good agreement (weighted kappa: 0.91 and 0.94 for the Afinion AS100 vs. Cholestech LDX and Afinion AS100 vs. laboratory method, respectively) for cardiovascular disease risk calculation using QRISK2. Conclusions Point of care testing can support a ‘one stop shop’ approach by providing rapid, reliable results. The Afinion AS100 analyser provides a multi-analyte platform and compares well with laboratory-based methods and another well-established point of care testing analyser.

HDL genetic defects.

High density lipoprotein cholesterol (HDL-C) and its related apolipoproteins form part of the reverse cholesterol transport system that removes excessive cholesterol from the periphery to the liver. Many transport proteins and enzymes that are involved in this process are susceptible to genetic defects that influence plasma HDL-C concentrations and HDL function. The HDL-C concentration in the blood may not be as important as the function of this lipid fraction. The genetic defects affecting plasma HDL-C concentrations do not always show a consistent relationship with atherosclerosis. Familial hypoalphalipoproteinaemia is associated with mutations in genes responsible for the transport proteins or the enzymes involved in the biogenesis of HDL-C. Inheritance of a Milano mutation of apolipoprotein A1 decreases the risk of atherosclerotic disease despite low circulating levels of HDL-C. Tangier disease and Fish Eye disease are caused by mutations in the ATP binding cassette A1 (ABCA1), a transport protein, and lecithin cholesterol acyl transferase (LCAT), an enzyme, involved in the esterification of cholesterol, respectively. Patients with these conditions have very low levels of HDL-C concentration. The association between both these conditions and the risk of cardiovascular disease (CVD) is variable and inconsistent. Understanding the molecular mechanism of HDL biogenesis not only helped in defining the pathophysiology of low and high HDL-C syndromes, but also in developing new treatment options to raise HDL-C levels.

Short-term abstinence from alcohol and changes in cardiovascular risk factors, liver function tests and cancer-related growth factors: a prospective observational study

Objective To assess changes in metabolic risk factors and cancer-related growth factors associated with short-term abstinence from alcohol. Design Prospective, observational study. Setting Single tertiary centre. Participants Healthy subjects were recruited based on intention to: (1) abstain from alcohol for 1 month (abstinence group), or (2) continue to drink alcohol (control group). Inclusion criteria were baseline alcohol consumption >64 g/week (men) or >48 g/week (women). Exclusion criteria were known liver disease or alcohol dependence. Primary and secondary outcome measures The primary outcome was change in insulin resistance (homeostatic model assessment (HOMA) score). Secondary outcomes were changes in weight, blood pressure (BP), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) and liver function tests. Primary and secondary outcomes were adjusted for changes in diet, exercise and cigarette smoking. Results The abstinence group comprised 94 participants (mean age 45.5 years, SD ±1.2) and the control group 47 participants (mean age 48.7 years, SD ±1.8). Baseline alcohol consumption in the abstinence group was 258.2 g/week, SD ±9.4, and in the control group 233.8 g, SD ±19.0. Significant reductions from baseline in the abstinence group (all p<0.001) were found in: HOMA score (−25.9%, IQR −48.6% to +0.3%), systolic BP (−6.6%, IQR −11.8% to 0.0%), diastolic BP (−6.3%, IQR −14.1% to +1.3%), weight (−1.5%, IQR −2.9% to −0.4%), VEGF (−41.8%, IQR −64.9% to −17.9%) and EGF (−73.9%, IQR −86.1% to −36.4%). None of these changes were associated with changes in diet, exercise or cigarette smoking. No significant changes from baseline in primary or secondary outcomes were noted in the control group. Conclusion These findings demonstrate that abstinence from alcohol in moderate–heavy drinkers improves insulin resistance, weight, BP and cancer-related growth factors. These data support an independent association of alcohol consumption with cancer risk, and suggest an increased risk of metabolic diseases such as type 2 diabetes and fatty liver disease.

Lipoprotein X in autoimmune liver disease causing interference in routine and specialist biochemical investigations

ABSTRACT Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are chronic, immune-mediated diseases which may be associated with the presence of lipoprotein X (LpX). This is an abnormal lipoprotein resulting in marked elevation of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) concentration. LpX is rich in free cholesterol (FC) and phospholipids (PL) and low in esterified cholesterol (CE). We describe two cases with florid lipid stigmata and presence of LpX. A patient with PBC presented with itching and palmar xanthomata. TC = 55.5 mmol/L, direct LDL-C = 14.9 mmol/L, high-density lipoprotein cholesterol (HDL-C) = 0.5 mmol and triglycerides (TG) = 11.3 mmol/L. Lipoprotein electrophoresis (LPE) showed the presence of LpX. An apolipoprotein E (Apo E) phenotype and genotype reported E2E3 and E3E3 isoforms, respectively. A patient with PSC presented with itchy eruptive xanthomata. TC = 22.8 mmol/L, calculated LDL-C = 21.7 mmol/L, HDL-C = 0.2 mmol/L and TG = 1.6 mmol/L. LPE was normal. Both Apo E phenotype and genotype showed E2E3 isoforms. Both patients were treated with statins and showed resolution of lipid stigmata and improvement of lipid parameters, including PL, FC and LpX. In the first case, Apo E phenotype showed an E3E3 phenotype like the genotype following the decrease in LpX. LpX can interfere with other routine biochemical measurements, falsely increase TC and LDL-C levels and in our patient with PBC, we believe that LpX interfered with Apo E phenotype analysis. This has not been previously described.