A cost-utility analysis of decompressive hemicraniectomy versus medical treatment in the management of space-occupying brain oedema post middle cerebral artery infarction.

BACKGROUND AND PURPOSE: Data from randomly controlled trials have indicated that a decompressive hemicraniectomy is more clinically effective than medical treatment in the management of space-occupying brain oedema post middle cerebral artery infarction. This economic evaluation compares the impact of the two options in the UK. No recent study has conducted an economic evaluation on this topic for the UK. METHOD: A cost-utility analysis over a time period of 1 year was used, measuring benefits in terms of quality adjusted life years (QALYs) and costs in pound sterling, discounted to 2015 prices. The evaluation was from the perspective of the National Health Service, the largest healthcare provider in the UK. RESULTS: The cost-utility analysis found an incremental cost effectiveness of £116 595.10 for every QALY gained if patients were offered a decompressive hemicraniectomy compared to the best medical treatment. DISCUSSION: This is above the National Institute for Health and Care Excellence (NICE) 'cost-effective' threshold of £20 000-£30 000 per QALY, but lower mortality rates associated with the surgical alternative raises ethical considerations for healthcare providers in the UK.

Apolipoprotein C3 SstI polymorphism in the risk assessment of CAD.

Various population studies have reported the association of rare S2 allele of apolipoprotein C3 (APOC3) SstI polymorphism with hypertriglyceridemia (HTG) and coronary artery disease (CAD). We were the first to report an association of S2 allele with high triglyceride (TG) levels in healthy volunteers from Northern India. Since HTG is suggested to be a predominant risk factor for CAD among Indians, we have elucidated the relationship of APOC3 SstI polymorphism with the lipid profile and CAD. A total of 158 patients with > or = 70% stenosis in one or more coronary artery (angiographically proven CAD patients), 35 subjects with < 70% stenosis (NCAD) and 151 normal controls (free of heart disease) from Northern plains of India were recruited in the study. DNA samples were analyzed by polymerase chain reaction (PCR) followed by SstI digestion. Lipid profile was estimated by enzymatic kit. We found a strong association of S2 allele with high TG levels, which was more significant in patients. Prevalence of S2 allele in normal controls and CAD patients were comparable, despite the fact that mean TG level was significantly higher in patients. A greater insight into this observation revealed that the prevalence of high TG, if not coupled with other risk factors (like high total cholesterol, low HDL), was comparable in patients and controls. Thus, our study reveals that rare S2 allele may be employed as a susceptibility marker for high TG. However, high TG or S2 allele alone may not contribute to the etiology of CAD.

Lipoprotein(a) as a marker of coronary artery disease and its association with dietary fat.

OBJECTIVE: The main objectives of the study were to evaluate the effect of dietary fat on plasma lipoprotein(a) [Lp(a)] levels and to study the potential of Lp(a) as a more reliable marker for CAD compared to other lipids and lipoproteins. METHODS: Twenty CAD patients and 20 healthy controls were recruited for the study. Their fasting plasma Lp(a) levels and complete lipid profile were assayed. The fat intake was calculated using 24 hours dietary recall method. The patients and controls were each divided into two subgroups: Group A consuming dietary fat > 30% and Group B consuming dietary fat < or = 30% of the total kilo-calories/day. RESULTS: Results indicated that plasma Lp(a), total serum cholesterol (TC), tryglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and LDL-C/HDL-C ratio of CAD patients were significantly higher than the controls. High fat intake was found to be associated with higher plasma Lp(a) levels (p<0.05) in patients only. No significant correlation was found between Lp(a) levels and other conventional lipoproteins. CONCLUSION: The lack of correlation between Lp(a) and other lipoproteins indicates its potential as an independent risk factor for CAD. High fat intake led to higher plasma Lp(a) levels in patients; hence it would be worthwhile to evaluate the effect of quality and quantity of fat intake on plasma Lp(a) levels in a larger sample size.

Study of apolipoproteinc3 Sstl polymorphism in healthy volunteers from Northern India.

Several studies including a small case-control (hypertriglyceridemic/normotriglyceridemic individuals) study by us revealed close association between rare S2 allele ofAPOC3 Sstl polymorphism and hypertriglyceridemia. With the understanding that Asian Indians are highly vulnerable to the adverse effects of hypertriglyceridemia, we extended the investigation and studied the frequency distribution of this polymorphism in 216 healthy volunteers from Northern plains of India. We found that more than 50% of the study population had one or two S2 allele. This may suggest that a larger fraction of this population is genetically predisposed to hypertriglyceridemia.

Apolipoprotein C3 SstI polymorphism and triglyceride levels in Asian Indians.

BACKGROUND: A close association between Sst I polymorphism in the 3' untranslated region of the apolipoproteinC3 (APOC3) gene and levels of plasma triglycerides (TG) had been reported by different investigators. Hypertriglyceridemia(HTG) is a known risk factor for coronary artery disease (CAD) in the context of Asian Indians. We conducted a study on the relationship between APOC3 SstI polymorphism (S1S1, S1S2 and S2S2 genotypes) and plasma TG levels in a group of 139 male healthy volunteers from Northern India. METHODS: DNA samples were analyzed by polymerase chain reaction (PCR) followed by SstI digestion. Digested PCR products were run on 3% agarose gel and visualized by ethidium bromide staining. RESULTS: Rare S2 allele was highly prevalent in our study population (0.313) as compared to the Caucasians (0.00-0.11). The genotypic distribution was in agreement with Hardy-Weinberg equilibrium. S2 allele was almost two times more prevalent in the HTG group (N = 34) as compared to NTG group (N = 105) (p = 0.001). Multiple logistic regression revealed S1S2 individuals had age-adjusted odds ratio of 2.43 (95%CI = 0.99-6.01, p = 0.054) and S2S2 had 9.9 (95%CI = 2.66-37.29, p = 0.0006) for developing HTG in comparison to S1S1 genotype. CONCLUSIONS: Our study shows a significant association between rare S2 allele and HTG in Asian Indians.

Polymorphism (C677T) in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene: A preliminary study on north Indian men.

An elevated level of plasma homocysteine, sulfur containing amino acid generated through demethylation of methionine has been widely accepted as a risk factor for cardiovascular disease (CVD). The increase can result from genetic and/or nutrient related disturbances in the remethylation or transsulfuration pathways for homocysteine metabolism. A common mutation (C677T) in the gene encoding for the enzyme 5, 10-methylenetetrahydrofolate reductase (MTHFR) or deficiency of the B vitamins namely folic acid, B(12), B(6) can lead to hyperhomocysteinemia.In the present study, we have investigated the incidence of the (C677T) MTHFR polymorphism in the North Indian males. 141 angiographically proven coronary artery disease (CAD) patients and 55 age and sex matched healthy volunteers were examined for the association between MTHFR gene polymorphism and CAD. The MTHFR genotyping was performed using polymerase chain reaction (PCR) followed by restriction-isotyping with Hinf 1 endonuclease. A trend for higher 'T' allele frequency (0.19) was observed in patients than in controls (0.16). However no significant association was found between C677T mutation and CAD severity. The lack of statistical significance could be due to the small sample size studied. Hence a larger study including various ethnic groups is warranted.

Apolipoprotein(a) polymorphism and its association with plasma lipoprotein(a) levels: a north Indian study.

Elevated levels of lipoprotein(a) has been regarded as an independent risk factor for coronary, peripheral and cerebral atherosclerosis. The enormous intra-personal variation in the plasma concentration of lipoprotein(a) is almost entirely controlled by the apolipoprotein(a) i.e. gene locus on the chromosome 6q 26-27. The apolipoprotein(a) molecule is highly polymorphic and is known to exist in multiple, genetically determined isoforms. These polymorphisms may be responsible for difference in promoter activity, variable size of apolipoprotein(a) and thereby variation in plasma lipoprotein(a) concentration. We studied the effect of two types of polymorphisms, (i) variation in length of the pentanucleotide repeat in the 5' flanking region starting -1373 bp upstream of AUG codon, and (ii) the Kringle-4 type 2 size polymorphism, on plasma lipoprotein(a) levels in North Indian population. The study group consisted of 88 angiographically assessed male coronary artery disease patients (age range 30-70 years) and 83 age- and sex-matched healthy controls. The pentanucleotide repeat polymorphism was analysed using polymerase chain reaction. In all, 8/11 pentanucleotide repeat isoforms were observed. Using SDS-agarose gel electrophoresis and immunoblotting isoforms having 12-50 Kringle-4 type 2 repeats were detected. Our study indicates a strong association of elevated plasma lipoprotein(a) concentration with coronary artery disease. An inverse correlation was seen between lipoprotein concentration and isoform size for both the pentanucleotide repeat polymorphism and the Kringle-4 type 2 polymorphisms; statistically significant difference (p = 0.001) was, however, observed only for the later.

Serum levels of lipoprotein (a) and other lipids in angiographically defined coronary artery disease patients and healthy blood bank donors.

Lipoprotein (a) (Lp(a)) and other lipid values have been correlated with angiographically defined [table: see text] coronary artery disease. To study this relationship in Indian patients, plasma levels of Lipoprotein (a) and other lipids were assessed in 74 patients undergoing Coronary arteriography and also in 53 age and sex matched healthy male blood bank donors who served as controls. Total cholesterol (mg/dl) (211 +/- 56 vs 186 +/- 43; p < 0.001), low density lipoprotein Cholesterol (mg/dl) (117 +/- 40 vs 88 +/- 29; p > 0.001) and low density lipoprotein/high density lipoprotein cholesterol ratio (2.6 +/- 0.8 vs 2.2 +/- 0.9; p < .001) were significantly higher in patients than controls. High density lipoprotein-cholesterol (mg/dl) (43.5 +/- 6 vs 42.1 +/- 7; p-ns) very low density lipoprotein-cholesterol (mg/dl) (49.7 +/- 17 vs 56.1 +/- 25; p-ns) and triglycerides (mg/dl) (155 +/- 101 vs 167 +/- 88; p-ns) were not statistically different in two groups. Lipoprotein (a) levels showed highly skewed distribution. Patients (n = 74) showed almost five fold higher lipoprotein (a) levels (mg/dl) as compared to controls (n = 53) [105 +/- 565 vs 23 +/- 76]. Patients with very high lipoprotein (a) levels [values of more than 40 mg/dl] (n = 18) had high density lipoprotein cholesterol and total cholesterol significantly lower than rest of the patient group. [high density lipoprotein cholesterol (mg/dl) 41.00 +/- 3.7 vs 44 +/- 6.4; p < 0.01 and total cholesterol (mg/dl) 192 +/- 34 vs 217 +/- 53; p < 0.05].

Interrelationship between angiographically defined coronary artery disease, plasma insulin levels and lipids in Indian patients.

We investigated the interrelationship between plasma insulin levels, various lipoproteins and coronary artery disease. No significant differences were observed on comparing patients with controls for plasma insulin, high density lipoprotein cholesterol, fasting blood sugar levels and triglyceride levels. However patients showed significantly higher levels of total cholesterol and low density lipoprotein cholesterol compared with controls. No significant differences were observed on comparing patients of multivessel disease with single vessel disease in serum insulin or various lipid subfractions. In addition, there was no correlation between serum insulin quartiles and various biochemical parameters. In conclusion, in this cross-sectional study plasma insulin levels failed to show any significant association with severity and extent of coronary artery disease. Further there was no correlation of various lipid parameters with insulin quartiles.

LP(a) phenotypes and levels in angiographically proven coronary heart disease patients and controls.

Lipoprotein Lp(a) excess has been identified as a powerful predictor of premature atherosclerotic vascular diseases. To evaluate this in a North-Indian population, 130 CAD patients and 130 controls were analyzed. The size of the apo(a) phenotypic isoforms was inversely proportional to Lp(a) concentrations. The mean concentration of Lp(a) in the CAD patients was 42±34 mg/dl whereas in the normal subjects it was much lower, 27±27 mg/dl. 157 subjects out of the total 260 subjects showed plasma levels of >20mg/dl. The frequency of high Lp(a) levels was much higher in patients(73%) than controls (43%). These data suggest (1) that there is heterogeneity of the Lp(a) polymorphism, (2) Higher Lp(a) levels were found in patients than in the controls, (3) Patients showed 1.5 fold increase in Lp(a) levels as compared to the controls. We conclude that low molecular weight apo(a) isoforms are significantly associated with increased risk of CAD in the North-Indian population.

Influence of two apo A4 polymorphisms at codons 347 and 360 on non-fasting plasma lipoprotein-lipids and apolipoproteins in Asian Indians.

Apolipoprotein A-IV (apo A-IV, protein; apo A4, gene) is a major constituent of triglyceride-rich and high-density lipoprotein particles and may, therefore, play an important role in lipid metabolism. We studied the distribution of two apo A4 polymorphisms at codons 347 (alleles A and T) and 360 (alleles 1 and 2) in relation to plasma lipoprotein-lipid and apolipoprotein levels in 176 non-fasting male blood donors from New Delhi, Northern India. The frequencies of the T allele at codon 347 and the 2 allele at codon 360 were 0.12 and 0.03 respectively. Carriers of the T allele (AT and TT genotypes) had significantly lower plasma total cholesterol (P = 0.04) and low density lipoprotein (LDL)-cholesterol (P = 0.02) levels than individuals homozygous for the A allele (AA genotype). The codon 347 polymorphism explained 2.2 and 2.6% of the phenotypic variation in total cholesterol and LDL-cholesterol, respectively. The 2 allele at codon 360 was associated with marginally reduced plasma LDL-cholesterol (P = 0.09) and increased triglyceride (P = 0.05) levels compared to the 1 allele. To further elucidate the combined effects of the two polymorphism we constructed two-site haplotypes. The haplotype data showed a stronger influence and explained 3.0 and 5.2% of the phenotypic variation in total cholesterol and LDL-cholesterol, respectively. The two uncommon haplotypes, T1 and A2, were associated with 24.2 and 23.5 mg/dl lower total cholesterol and 22.5 and 42.0 mg/dl lower LDL-cholesterol levels, respectively. The accentuated effect of apo A4 polymorphisms on non-fasting plasma cholesterol suggest that apo A-IV may play an important role in regulating the postprandial metabolism of lipoproteins.

Correlation of lipoprotein (a) to angiographically defined coronary artery disease in Indians.

Lipoprotein (a) [Lp(a)] levels have been correlated with angiographically defined coronary artery disease (CAD). Pattern of Lp(a) distribution in various racial groups is different. To study this relationship in Indian patients, plasma levels of Lp(a) and other lipid values were assessed in 101 patients undergoing coronary arteriography. Lp(a) concentration was higher in CAD group (n = 77) compared to normal coronary artery group (n = 24) (26.83 +/- 22.09 mg/dl vs. 15.07 +/- 14.61 mg/dl, P < 0.05). Lp(a) values had graded association with CAD. In Lp(a) quartile of < 5 mg/dl, 66.7% patients had CAD; in Lp(a) quartile of 5-25 mg/dl, 69.0% had CAD; Lp(a) quartile of 26-75 mg/dl, 87.5% had CAD; and in Lp(a) quartile of > or = 76 mg/dl, all patients had CAD. High density lipoprotein (HDL) cholesterol was higher in the normal coronary artery group as compared to CAD group (45.25 +/- 8.26 mg/dl vs. 41.83 +/- 16.47 mg/dl; NS). In HDL quartile of < 35 mg/l, 88.9% patients had angiographically defined CAD. Plasma values of total cholesterol, triglycerides (TG), apolipoprotein-A1 (Apo-A1), apolipoprotein-B (Apo-B), low density lipoprotein (LDL) cholesterol, LDL/HDL cholesterol ratio and Apo A1/B ratio were not significantly different in the groups with normal coronary arteries and CAD. Our results indicate that the measurement of Lp(a) provides a better marker for predicting the presence of angiographically defined CAD as compared to traditional measures.

Distribution of apolipoprotein E genotypes in Asian Indians, Hungarians, and Papua New Guineans.

We report here the distribution of apo E genotypes and allele frequencies in Asian Indians, Hungarians, and Papua New Guineans using the DNA based analysis. Frequency of the apo E4 allele was thrice as high in Papua New Guineans as compared to the Caucasians. The rare apo E2 allele was also present in higher frequency in the Papuas as compared to other populations.

Effect of MaxEPA (fish oil) on lipoproteins and its receptors in hypercholesterolemic rabbits.

The effect of dietary MaxEPA (fish oil) supplementation on cholesterol induced hypercholesterolemia in rabbits was investigated. Rabbits were fed 0.1% cholesterol enriched diet for one month and randomly divided into two groups (I and II). Group I was continued on a 0.1% cholesterol rich diet whereas group II in addition to cholesterol supplementation received MaxEPA (2.5 g/kg body weight) per day for a period of two months. B-VLDL-C, LDL-C and total serum peroxide levels (TBARS) were significantly higher in group II animals as compared to group I. No statistical difference was found in the number of hepatic B-VLDL binding sites between group I and II. Microscopic examination of the aorta showed an increase in the number of intimal foam cells in MaxEPA treated group, a result that may be linked to increase in total cholesterol, plasma TBARS and with simultaneous reduced hepatic uptake of B-VLDL.

Relation between alcohol intake, lipoproteins and coronary heart disease: the interest continues.

This paper reviews the much discussed association between alcohol intake, lipoproteins and coronary heart disease (CHD). Epidemiological studies have consistently shown an inverse trend between low to moderate alcohol consumption and CHD. Such a protective effect of alcohol against atherosclerosis has been associated with the elevated concentration of HDL-cholesterol induced by alcohol. However, the underlying mechanisms whereby alcohol drinking enhances HDL-cholesterol levels are not yet fully clear. Various lifestyle variables, namely diet, smoking, hypertension, body mass index and exercise, can affect the lipoprotein status in both users and non-users of alcohol.

Effect of alcohol on serum lipids & lipoproteins in male drinkers.

The evaluation of the effect of moderate and high doses of ethanol on the serum levels of triglyceride (TG), total cholesterol (TC), cholesterol content of very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL), HDL2, HDL3 subfractions and apoproteins: apo-AI and apo-B was undertaken in 45 (25 controls, 10 moderate and 10 high dose drinkers) healthy males. The results of this preliminary study showed a significant rise in total HDL-cholesterol and apo-AI levels of alcoholics of both the groups. Out of the two subfractions, HDL2 appeared to be induced more. Increased levels of atherogenic lipids (TG, VLDL-chol., LDL-chol. and apo-B) were found in high as well as moderate drinkers. Our results suggest that the benefit of alcohol intake need to be weighed carefully against its considerable risks.