Pro-protein convertase subtilisin/kexin 9 concentrations correlate with coronary artery disease atheroma burden in a Pakistani cohort with chronic chest pain.

OBJECTIVE: To determine the relationship between proprotein convertase subtilisin kexin 9 (PCSK9) levels and atheroma burden in Pakistanis presenting to an ambulatory centre with chest pain. METHODS: A prospective matched case-control study of 400 patients selected for presence/absence of angiographic disease referred between 2001 and 2003. A comprehensive cardiovascular disease risk factor profile was assessed including demographics, environmental and biochemical risk factors including insulin resistance and PCSK-9 levels. Coronary atheroma burden was quantified by Gensini score. RESULTS: In this population, PCSK-9 levels were weakly correlated (r = 0.23) with male gender (p = 0.06) and number of diabetes years (p = 0.09), and inversely with log10 of lipoprotein (a) concentration (p = 0.07) but not LDL-C. In multiple regression analysis, Gensini score was associated with age (p = 0.002), established angina (p = 0.001), duration of diabetes (p = 0.05), low HDL-C (p < 0.001), lipoprotein (a) (p = 0.01), creatinine (p < 0.001), C-Reactive Protein (p = 0.02) and PSCK-9 (p = 0.05) concentrations. PCSK9 added to the regression model. Neither total cholesterol nor LDL-C were significant risk factors in this study. CONCLUSIONS: Proprotein convertase subtilisin kexin 9 concentrations are correlated with atheroma burden in Indian Asian populations from the sub-continent, not taking statin therapy, independent of LDL-C or other CVD risk factors.

The lipaemic index: clinical observations.

The lipaemic index can be used to assess whether or not blood samples are suitable for laboratory analysis. However, little is known about which patients have a raised lipaemic index. In this article we study patient demographics and serum lipid concentrations in samples showing a raised lipaemic index. Of the 4271 patient samples measured in the month of July 2014, a total of 310 had a lipaemic index 0.4. Blood samples showing a raised lipaemic index were studied in a retrospective patient case review of laboratory results. Overall, 7.3% of all samples measured had a raised lipaemic index 0.4. This study found that males were more likely to have a high lipaemic index (56%) and neonates were the group most frequently producing lipaemic samples (30.6%). The correlation between the lipaemic index and the triglyceride concentration showed an r2 value of only 0.37 (r = 0.61), and the correlation between cholesterol and lipaemic index showed an r2 value of 0.16 (r = -0.41). Male and neonatal samples were most likely to show a raised lipaemic index. There was a positive correlation between sample triglyceride and lipaemic index and an inverse correlation with cholesterol concentration and the lipaemic index, although this did not account for all the variance. Thus, other factors may also be important in the expression of the lipaemic index.

Angiographic coronary artery disease and high-sensitivity troponin-T in a native Pakistani cohort presenting with chronic chest pain.

OBJECTIVE: To determine the relationship between troponin-T levels and atheroma burden in Pakistanis presenting to an ambulatory centre with chest pain. METHODS: A prospective case-control study of 400 patients selected for presence/absence of angiographic disease referred between 2001 and 2003. A comprehensive cardiovascular disease (CVD) risk factor profile was assessed including demographics, environmental and biochemical risk factors including insulin resistance and troponin-T levels. Coronary atheroma burden was quantified by Gensini score. RESULTS: Clinically significant elevated troponin-T levels (> 30 pmol/l) were found in 40 patients (10%) with equal numbers in groups selected with or without angiographic disease. Troponin-T elevation (> 13 pmol/l) was present in 59 vs. 47 patients (30% vs. 24%; p = 0.04). Troponin-T levels did not correlate with any measured demographical, environmental, drug therapy or biochemical risk factor. No difference was found in concentrations of lipids, apolipoproteins, insulin resistance, C-reactive protein or sialic acid in cohorts stratified by troponin-T concentrations. In univariate analysis comparing patients with high (> 30 pmol/l) and low troponin-T levels (< 13 pmol/l) higher plasma total protein (91 g/l vs. 85 g/l; p = 0.01), increased immunoglobulin levels (41 g/l vs. 36 g/l; p = 0.02) and prevalence of hyperparathyroidism (40% vs. 21%; p = 0.04) were associated with higher troponin-T concentrations. CONCLUSIONS: This study shows that measurement of troponin-T is not an alternative to imaging in an Indian asian population, but that it does identify a separate potentially high-risk population that would not be identified by the use of imaging alone which is potentially at higher risk of CVD events.

The risks of absolute medical confidentiality.

Some ethicists argue that patient confidentiality is absolute and thus should never be broken. I examine these arguments that when critically scrutinised, become porous. I will explore the concept of patient confidentiality and argue that although, this is a very important medical and bioethical issue, this needs to be wisely delivered to reduce third party harm or even detriment to the patient. The argument for absolute confidentiality is particularly weak when it comes to genetic information and inherited disease.

A prospective case-controlled cohort study of endothelial function in patients with moderate to severe psoriasis.

BACKGROUND: There is well-documented evidence that patients with moderate and severe psoriasis have a significantly increased risk of cardiovascular disease (CVD). While this risk can, at least in part, be attributed to the high prevalence of traditional risk factors in the population with psoriasis, some epidemiological evidence suggests it may be independent of these. OBJECTIVES: This prospective, case-controlled study investigates whether psoriasis is a risk factor for CVD using two, validated, sensitive markers of CVD, endothelial dysfunction and high-sensitivity C-reactive protein (hsCRP). METHODS: Patients were recruited from a tertiary referral psoriasis clinic and exclusion criteria included established CVD and/or conventional risks for CVD. Preclinical CVD was assessed using flow-mediated brachial artery dilatation, which measures endothelial dysfunction, and hsCRP, a serological marker of atherosclerosis. RESULTS: Sixty-four patients (22%) out of a total of 285 consecutive patients attending the severe psoriasis clinic were entered into the study. One hundred and sixty-one (56%) were excluded following identification of cardiovascular risk; 39 of the 161 (24%) had at least two cardiovascular risk factors. A further 16 (6%) patients were excluded because of established CVD. No statistically significant difference in endothelial dysfunction was observed between patients with psoriasis (n = 60) and healthy controls (n = 117) (P = 0·508). The hsCRP level was, however, significantly elevated in the psoriasis group (2·828 mg L(-1), SEM 0·219; controls 0·728 mg L(-1), SEM 0·142; P < 0·05). CONCLUSION: This large, investigative study is the first to assess endothelial function in patients with psoriasis after exclusion of traditional risk factors for CVD. These data suggest that psoriasis per se is not a risk factor for CVD and that elevated hsCRP is possibly independent of atheroma risk. There was a high prevalence of traditional risk factors in our population with severe psoriasis.

Insulin resistance phenotypes and coronary artery disease in a native Pakistani cohort.

OBJECTIVE: To determine the relationship between insulin resistance (IR) and atheroma burden in Pakistanis. METHODS: A prospective case-control study of 400 patients selected for the presence/absence of angiographic disease. Coronary atheroma burden was quantified and IR and cardiovascular risk factors were measured. RESULTS: The patients were divided into two groups by QuickI score. Waist circumference (90 +/- 10 vs. 90 +/- 9 cm; p = 0.7) was similar but the groups differed in body mass index (26.5 +/- 3.7 vs. 24.2 +/- 3.5 kg/m(2); p < 0.001) and waist:hip ratio (0.94 +/- 0.09 vs. 0.90 +/- 0.06; p < 0.001). Lipid parameters showed similar high-density lipoprotein cholesterol (HDL-C) (0.77 +/- 0.23 vs. 0.82 +/- 0.22 mmol/l; p = 0.1) differences in triglycerides [1.32 (0.08-3.98) vs. 1.12 (0.37-3.61) mmol/l; p = 0.01], but no difference in low-density lipoprotein cholesterol (LDL-C) (2.75 +/- 1.00 vs. 2.90 +/- 0.94 mmol/l; p = 0.14). In insulin-resistant patients C-reactive protein (CRP) [6.8 (0.3-175.1) vs. 3.9 (0.2-57.9) mg/l: p < 0.001], sialic acid (82 +/- 14 vs. 77 +/- 15 mg/l; p < 0.001) aspartate transaminase [24 (7-171) vs. 21 (7-83) IU/l; p < 0.001] and gamma-glutamyl transferase [27 (8-482) vs. 21 (7-168) IU/l; p = 0.005] levels were increased. In insulin-resistant patients (n = 187), coronary artery disease (CAD) burden correlated (r = 0.55) with age (beta = 1.62; p < 0.001), HDL-C (beta = -53.2; p < 0.001), lipoprotein (a) (beta = 11.4; p = 0.007), smoking (beta = 7.98; p = 0.004), CRP (beta = 6.06; p = 0.03) and QuickI index (beta = -146; p = 0.04). In contrast in insulin-sensitive patients (n = 178) CAD burden (r = 0.46) correlated with LDL-C (beta = 10.0; p = 0.02), CRP (beta = 7.13; p = 0.03), HDL-C (beta = -38.1; p = 0.03), and weakly with age (beta = 0.73; p = 0.07) and smoking (beta = 5.52; p = 0.09). CONCLUSIONS: Indian Asians show a dichotomous insulin-resistance phenotype. Atheroma is associated with low HDL-C and inflammation associated in all but LDL-C is a factor in the insulin sensitive in contrast to age and extent of IR in the insulin resistant.

Elevated serum sialic acid concentration in NIDDM and its relationship to blood pressure and retinopathy.

OBJECTIVE: In view of the possible link between serum sialic acid and cardiovascular disease in the general population, we investigated whether serum total and lipid-associated sialic concentrations are elevated in NIDDM patients compared with normal subjects. We also investigated how sialic acid levels relate to glycemic control, blood pressure, microalbuminuria, retinopathy, and serum lipid levels. RESEARCH DESIGN AND METHODS: We selected 20 NIDDM patients at random and matched them for age and sex with 20 normal subjects. The patients also had a similar BMI as the control subjects. A first morning blood sample was taken for sialic acid, glucose, fructosamine, and lipid analysis, as was a first morning urine sample for assessment of microalbuminuria. Retinopathy was assessed by fundoscopy. RESULTS: Both total and lipid-associated sialic acid levels were elevated in the NIDDM patients compared with control subjects (mean +/- SD, total: 0.74 +/- 0.11 vs. 0.60 +/- 0.22 g/L, P < 0.02; lipid-associated: 0.18 +/- 0.04 vs 0.12 +/- 0.04 g/L, P < 0.001). Total serum sialic acid was correlated with systolic blood pressure (r = 0.58, P < 0.01) and diastolic blood pressure (r = 0.58, P < 0.02). There was no significant relationship of total sialic acid with age, duration of diabetes, BMI, microalbuminuria, serum triglyceride, blood glucose, or serum fructosamine. A relationship of lipid-associated sialic acid levels and systolic blood pressure did not reach significance (P = 0.09). In 9 patients with background retinopathy with or without maculopathy, the total serum sialic acid concentration was higher than in those without retinopathy (0.81 +/- 0.09 vs. 0.69 +/- 0.10 g/L, P < 0.008). Lipid-associated sialic acid levels were similar in those with and without retinopathy. (The conversion factor for standard units to SI units is 1 gL = 3.2 mM.) CONCLUSIONS: Total serum sialic acid levels were significantly elevated in a relatively small group of NIDDM patients and were correlated with hypertension and retinopathy. A larger study of circulating sialic acid concentrations as a risk factor for the development or marker of diabetic angiopathy is therefore justified.

Serum sialic acid, a risk factor for cardiovascular disease, is increased in IDDM patients with microalbuminuria and clinical proteinuria.

OBJECTIVE: An elevated serum sialic acid concentration has recently been shown to be a potent cardiovascular risk factor in the general population. Because clinical proteinuria is associated with a high frequency of cardiovascular disease, and because microalbuminuria predicts the development of renal and cardiovascular disease in diabetes, we investigated whether serum sialic acid levels are increased in insulin-dependent diabetes mellitus (IDDM) patients with microalbuminuria or clinical proteinuria. RESEARCH DESIGN AND METHODS: We studied 23 patients with IDDM who had a normal urinary albumin excretion rate, 23 patients who had microalbuminuria, and 23 patients with clinical proteinuria. The patients were matched for age, sex, duration of diabetes, GHb levels, and body mass index (BMI). Fasting blood samples were taken for measurement of sialic acid, cholesterol, triglyceride, creatinine, and GHb. RESULTS: Serum sialic acid was significantly higher in the microalbuminuric patients compared with the normoalbuminuric group (mean +/- SD: 1.93 +/- 0.26 vs. 1.76 +/- 0.27 mM, P < 0.01). Moreover, serum sialic acid was also significantly higher in the group with clinical proteinuria compared with the microalbuminuric patients (2.34 +/- 0.24 vs. 1.93 +/- 0.26 mM, P < 0.001). Serum sialic acid was not related independently to age, BMI, diabetes duration, GHb, blood pressure, serum cholesterol, triglyceride, or creatinine concentration in any of the diabetic groups. CONCLUSIONS: These observations suggest that the serum sialic acid concentration is raised in IDDM patients with both microalbuminuria and clinical proteinuria and may play a role as a cardiovascular risk factor or disease marker in these conditions.

Serum sialic acid concentration and coronary heart disease in NIDDM.

OBJECTIVE--To examine the association between serum sialic acid concentrations and coronary heart disease (CHD) in a cross-sectional study of non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS--NIDDM patients (n = 145) attending a diabetic clinic were studied. CHD status was assessed by questionnaire and electrocardiogram coding, and potential risk factor assessment included measurement of fasting serum lipid and lipoprotein concentrations, blood pressure, and urinary albumin excretion rate (AER). RESULTS--Male NIDDM patients with CHD had a higher serum sialic acid level than those without CHD: 2.56 (2.24, 2.72) mmol/l vs. 2.24 (2.18, 2.30) mmol/l, P = 0.01, mean (95% confidence interval). They were also older, had a longer duration of diabetes, had a higher AER, had higher total triglyceride, very-low-density lipoprotein triglyceride and cholesterol, and lipoprotein(a) concentrations, and had a lower apolipoprotein A1 concentration. In an age adjusted multiple lipoprotein(a), hypercholesterolemia, and hypertension were associated with CHD. In women, only hypertension treatment was associated with CHD. CONCLUSIONS--There is a strong univariate association between elevated serum sialic acid and CHD in men (but not women) with NIDDM.

Relationship between plasma sialic acid concentration and microvascular and macrovascular complications in type 1 diabetes: the EURODIAB Complications Study.

OBJECTIVE: To test the hypothesis that an increased plasma concentration of sialic acid, a marker of the acute-phase response, is related to the presence of diabetic micro- and macrovascular complications in type 1 diabetes. RESEARCH DESIGN AND METHODS: We investigated the relationship between plasma sialic acid concentration and nephropathy, retinopathy, neuropathy, and coronary heart disease (CHD) in a cross-sectional survey of 1,369 people with type 1 diabetes. Subjects were participants in the EURODIAB IDDM Complications Study, which involved 31 centers in 16 European countries. RESULTS: There was a significantly increasing trend of plasma sialic acid with severity of retinopathy (P < 0.001 in men) and with degree of urinary albumin excretion (P < 0.001 men, P < 0.01 women). Plasma sialic acid correlated with increasing plasma creatinine concentration (P < 0.009 men, P < 0.0002 women), and men with neuropathy had a higher plasma sialic acid concentration than those without (P < 0.006). There was no significant correlation between plasma sialic acid and CHD in either sex. Elevated plasma sialic acid concentrations were also associated with several risk factors for diabetic vascular disease: diabetes duration, HbA1c, plasma triglyceride and cholesterol concentrations, waist-to-hip ratio, hypertension and smoking (in men), and low physical exercise (in women). In multiple logistic regression analysis, plasma sialic acid was independently related to proliferative retinopathy and urinary albumin excretion rate in men. CONCLUSIONS: We conclude that an elevated plasma sialic concentration is strongly related to the presence of microvascular complications in type 1 diabetes, especially retinopathy and nephropathy. Further study of acute-phase response markers and mediators as indicators or predictors of diabetic microvascular complications is therefore justified.

Plasma sialic acid and coronary artery atheromatous load in patients with stable chest pain.

Serum or plasma sialic acid and C-reactive protein have recently been shown to be cardiovascular risk factors. Our aim was to determine whether plasma sialic acid or C-reactive protein concentration correlate with atheromatous load on coronary angiography. Plasma sialic acid concentration and plasma C-reactive protein concentration were determined in 128 consecutive patients attending day case coronary angiography. Patients were excluded for previous coronary angioplasty, coronary artery bypass grafting, recent myocardial infarction, acute or chronic inflammatory disease and proximal occlusions precluding analysis of distal coronary anatomy. Total cholesterol, triglyceride, HDL cholesterol and glucose concentrations were assayed on fasting samples of venous blood. Angiograms were graded according to a semisubjective scoring system. There was no significant correlation between plasma sialic acid (r = 0.19, P = 0.07), or C-reactive protein concentration (r = 0.17, P = 0.13) and atheromatous load. There was no significant correlation between sialic acid (P = 0.13), or C-reactive protein concentration (P = 0.32) and the number of diseased coronary vessels. The difference in plasma sialic acid concentration between those with normal coronary angiograms and those with coronary artery disease did not reach significance (P = 0.08). Plasma sialic acid concentration correlated with C-reactive protein (r = 0.58, P = 0.0001), serum triglyceride (r = 0.32, P = 0.002), and blood cholesterol concentration (r = 0.22, P = 0.04). Plasma sialic acid concentration does not correlate with atheromatous load on coronary angiography in patients with stable angina.

Influence of sialic acid content of low-density lipoprotein particles on endothelium-dependent vasorelaxation in rabbit aorta.

Low-density lipoprotein (LDL) concentration in plasma is an important predictor for atherosclerosis, and desialylated LDL has been proposed to be particularly atherogenic. Atherosclerosis is also associated with vascular endothelial dysfunction. We therefore wished to test the hypothesis that removal of sialic acid residues from LDL increases its ability to inhibit endothelium-dependent vasorelaxation. We studied vasorelaxant responses to acetylcholine (ACh) in isolated rabbit aortic rings as a model of endothelium-dependent relaxation, in the presence or absence of LDL treated either with saline or with neuraminidase, to cleave sialic acid residues. Vasorelaxant responses to ACh were inhibited by 300 microg protein per ml saline-treated LDL (E(max) 77.5+/-4.5 vs. 89.7+/-2.2% in the absence of LDL, P<0.05). This inhibitory effect was not altered by neuraminidase treatment of LDL. In contrast, 300 microg protein per ml LDL, either saline- or neuraminidase-treated, did not affect vasorelaxant responses to the endothelium-independent dilator sodium nitroprusside. We found no correlation between sialic acid content of saline-treated LDL and its ability to inhibit endothelium-dependent vasorelaxation, in rabbit aortic rings, at a concentration of 300 microg protein per ml. Our results therefore suggest that sialic acid content is not an important determinant of the effect of LDL on vascular endothelium-dependent relaxation.

High-density lipoprotein cholesterol and triglyceride response with simvastatin versus atorvastatin in familial hypercholesterolemia.

The clinical and biochemical determinants of high-density lipoprotein (HDL) and triglyceride response to simvastatin and atorvastatin were assessed in 150 patients with severe hyperlipidemia treated in a randomized open-trial format design. Triglyceride reduction was only dependent on HDL:apolipoprotein A1, change in apolipoprotein B, and dose response, whereas an increase in HDL was dependent on initial LDL, change in LDL or dose response, and therapy with simvastatin.

Fibrinogen response with simvastatin versus atorvastatin in familial hypercholesterolemia.

The clinical and biochemical determinants of the fibrinogen response to simvastatin or atorvastatin therapy were assessed in 130 patients with severe polygenic or familial hypercholesterolemia treated in a randomized open-trial format design. Hyperfibrinogenemia was associated with atorvastatin, baseline fibrinogen, and initial concentration and change in concentration of apolipoprotein B or low-density lipoprotein cholesterol.

Skin tags and the atherogenic lipid profile.

This report details four patients who had skin tags, mainly on their torso, neck, and axillae, and who also displayed an abnormal lipid profile. All showed an increased serum triglyceride (fasting > 1.70 mmol/litre) and a decreased high density lipoprotein (HDL) cholesterol (< 1.1 mmol/litre in women and 1.0 mmol/litre for men) concentration. The displayed lipid profile is also known as the atherogenic profile and is associated with insulin resistance, type 2 diabetes mellitus, and an increased risk of cardiovascular disease. Two of the patients had impaired glucose tolerance and one had type 2 diabetes mellitus. Three of the individuals had coronary artery disease. Skin tags might be a useful clinical sign that could alert clinicians to screen such individuals for abnormal lipids, type 2 diabetes mellitus, and cardiovascular disease.

A paradoxical severe decrease in serum HDL-cholesterol after treatment with a fibrate.

There have been a handful of reports in the literature of a paradoxical decrease in serum high density lipoprotein (HDL)-cholesterol in patients on fibrate drugs. The reason for this decline in cardioprotective HDL-cholesterol is not known and may have potential deleterious effects on the patient. This report describes a decrease in serum HDL-cholesterol in a patient on both simvastatin and bezafibrate. This patient also developed abnormal renal function, probably interstitial nephritis. In addition, the literature of fibrate induced serum HDL-cholesterol decline is reviewed and possible mechanisms for this phenomenon discussed.

Serum sialic acid as an indicator of change in coronary artery disease.

We measured serum levels of total sialic acid (TSA) by an enzymatic method in 74 men who completed the St Thomas' Atherosclerosis Regression Study (STARS). Coronary artery disease (CAD) was assessed as the change (delta) in mean absolute width of coronary segments (MAWS) over 3 years by a computerized technique. Delta TSA was significantly correlated with delta MAWS (r = -.50, P < .001) after adjusting for age, blood pressure, smoking status, and plasma low-density lipoprotein (LDL) cholesterol. The relative risk of progression of CAD for a delta TSA exceeding 10 mg/dL as compared with a delta TSA not exceeding 10 mg/dL was 4.6 (95% confidence interval, 2.4 to 8.7). We conclude that serial measurement of serum TSA levels may be a useful indicator of the progression of CAD.