HIV infection and lipids.

PURPOSE OF REVIEW: We comment on the role of dyslipidaemia in cardiovascular disease (CVD) in HIV-infected patients. We have discussed various risk factors, including traditional CVD risk factors, HIV-related risk factors and antiretroviral therapy (ART)-induced dyslipidaemia. RECENT FINDINGS: HIV-infected individuals are prone to lipid and lipoprotein abnormalities as a result of the infection itself and the effect of ART. The older drugs used for the treatment of HIV were associated with an increased risk of these abnormalities. New therapies used to treat HIV are lipid friendly. Calculating CVD risk in the HIV population is complex due to the infection itself and the ART-related factors. The advancement in ART has helped to increase the life expectancy of HIV patients. As a result, a growing number of patients die of non-HIV related complications such as CVD, hepatic and renal disease. Outcome studies with intervention for dyslipidaemia in HIV are underway. SUMMARY: The implications of the above findings suggest that all patients with HIV should undergo a CVD risk assessment before starting ART. Appropriate lipid-friendly ART regimen should be initiated along with intervention for associated CVD risk factors (e.g. lipids, hypertension and smoking).

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.

Assessment of non-alcoholic fatty liver disease (NAFLD) severity with novel serum-based markers: A pilot study.

BACKGROUND/AIMS: Non-alcoholic fatty liver disease (NAFLD) represents a significant public health issue. Identifying patients with simple steatosis from those with non-alcoholic steatohepatitis (NASH) is crucial since NASH is correlated with increased morbidity and mortality. Serum-based markers, including adipokines and cytokines, are important in the pathogenesis and progression of NAFLD. Here we assessed the usefulness of such markers in patients with NAFLD. METHODS: This prospective, cross-sectional study included 105 adult patients with varying severity of NAFLD. Twelve serum-based markers were measured by 3 biochip platforms and 2 enzyme-linked immunosorbent assay (ELISA) methods. We also developed a NAFLD individual fibrosis index (NIFI) using the serum-based markers mostly correlated with fibrosis severity. RESULTS: Sixty-one out of 105 patients were male (58.1%) with mean age was 53.5 years. Higher Interleukin-6 (IL-6) increased (p = 0.0321) and lower Matrix Metalloproteinase-9 (MMP-9) serum levels (p = 0.0031) were associated with higher fibrosis as measured by Fibroscan® in multivariable regression analysis. Using receiver-operating characteristic (ROC) curve analysis for the NIFI, area under the curve for predicting Fibroscan values ≥ 7.2 kPa was 0.77 (95%CI: 0.67, 0.88, p<0.001), with sensitivity of 89.3%, specificity of 57.9% and a positive likelihood ratio of 2.8. CONCLUSIONS: Increasing fibrosis severity in NAFLD is associated with differential expression of IL-6 and MMP-9. NIFI could be valuable for the prediction of advanced NAFLD fibrosis and potentially help avoid unnecessary interventions such as liver biopsy in low-risk patients.

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.

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.

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.

Telomeres are shorter in myocardial infarction patients compared to healthy subjects: correlation with environmental risk factors.

Shorter telomeres have been reported in premature myocardial infarction (MI) patients. Our work aimed at confirming the association of shorter telomere with MI in two case-control studies and in familial hypercholesterolemia (FH) patients with coronary heart disease (CHD). The HIFMECH study compared 598 white male patients (<60 years) who survived a first MI and 653 age-matched controls from North and South Europe. Additionally, from the UK, 413 coronary artery bypass graft (CABG) patients and two groups of 367 and 94 FH patients, of whom 145 and 17 respectively had premature CHD, were recruited. Leukocyte telomere length (LTL) was measured using a real-time polymerase chain reaction-based method. In HIFMECH, LTL was significantly shorter in subjects from the North (7.99 kb, SD 4.51) compared to the South (8.27 kb, SD 4.14; p = 0.02) and in cases (7.85 kb, SD 4.01) compared to controls (8.04 kb, SD 4.46; p = 0.04). In the CABG study, LTL was significantly shorter (6.89 kb, SD 4.14) compared to the HIFMECH UK controls (7.53, SD 5.29; p = 0.007). In both samples of FH patients, LTL was shorter in those with CHD (overall 8.68 kb, SD 4.65) compared to the non-CHD subjects (9.23 kb, SD 4.83; p = 0.012). Apart from a consistent negative correlation with age, LTL was not associated across studies with any measured CHD risk factors. The present data confirms that subjects with CHD have shorter telomeres than controls and extends this to those with monogenic and polygenic forms of CHD.