Serum total cholesterol (TC), HDL-cholesterol (HDL-C) and A1, A2 and B apoprotein levels were determined in a population of 967 adults aged 25 to 64 years representative of the general population of the Bas-Rhin region localized in North-Eastern France. Age and sex were found to have a significant influence on most parameters studied; however, HDL-cholesterol, Apo A1, and Apo A2 were independent from age in males. HDL-cholesterol levels were consistently found to be higher in females than in males. Cholesterol, HDL-cholesterol, Apo A1, Apo A2 and Apo B levels, but not the HDL-cholesterol/cholesterol ratio, were higher in females above 45 years of age. A cholesterol level indicating increased cardiovascular risk, i.e., above 5.1 mmol/l, was found in 55% of males and 53% of females; HDL-cholesterol was under 0.9 mmol/l in 46% of males and 29% of females. The close linear correlations seen between cholesterol and Apo B (r = 0.820) and between HDL-cholesterol and Apo A1 (r = 0.580) were used to estimate theoretical threshold levels of apoproteins indicating increased risk: the Apo B level was greater than 0.77 g/l in 60% of males and 45% of females and the Apo A1 level was smaller than 1.58 g/l in 42% of males and 28% of females. Apo A2 level seems less useful as marker of increased risk. In conclusion, increased vascular risk due to unfavorable lipid profiles was common in the studied population especially among males and among females above 45 years of age. Apoproteins A1 and B reliably reflect cholesterol and HDL-cholesterol levels and can help evaluate cardiovascular risk.

Among nutrients, the role of water-soluble vitamins as genetic expression modulators has not been exhaustively stu-died. Relevant information is shown herein on the present state of the art in this field. For example, vitamin C deficiency leads to a decrease in mRNA levels of apolipoprotein A1 (Apo A1) in liver. Biotin participates in the regulation, both at mRNA and protein level, of the enzymes that participate in its own metabolic cycle and of enzymes that contribute to glucose metabolism. Thiamine regulates the expression of some genes that code for enzymes using thiamine diphosphate as cofactor. Thiamine deficiency diminishes the mRNA levels of transketolase and pyruvate dehydrogenase. It has been shown in riboflavin-deficient rats that FAD regulates some acetyl CoA dehydrogenases, producing a marked increase in mRNA levels. Nicotinamide positively regulates glyceraldehyde-3-phosphate dehydrogenase when NADH is added. Vitamin B6 modulates the expression of a variety of genes that respond to hormones. Vitamin B12 increases concentrations of the enzymatic protein methionine synthetase and doe not affect mRNA levels, which implies that this protein is regulated by its cofactor post-transcriptionally. Most mechanisms involved in these regulation examples are not known, which opens new research areas for the future.

BACKGROUND

Diabetes Mellitus (DM) is always a multifactorial metabolic disorder having a wide range of abnormalities in carbohydrate, lipid and protein metabolism. Dyslipidemia is a natural process of DM causing abnormal variations of different lipoproteins and it is one of the significant risk factors for Cardiovascular Disorder (CVD). There is a need to closely evaluate newer approaches in case of DM because even if dyslipidemia is treated, there is always a risk of CVDs in DM patients because of the hyperglycemia itself. So, lipid abnormalities should be assessed aggressively and treated as part of diabetes care. Apolipoprotein B100 (Apo B100), Apolipoprotein A1 (Apo A1) and Lipoprotein (a) {Lp(a)} are newer markers which are always welcome and necessary as many of the reported cases with normal conventional lipid profile have developed cardiac events.

OBJECTIVE

Study the correlation between glycemic control and the levels of Apo A1, Apo B100 and Lp(a).

METHODS

Total 56 patients of (DM) diagnosed on the basis of American Diabetic Association guidelines were recruited, out of which 28 were identified as uncontrolled-diabetic patients and remaining 28 as controlled-diabetics on the basis of Glycosylated HbA1c (HbA1c). The control group consisted of normal healthy 28 individuals. Apo B100, Apo A1 and Lp(a) along with traditional lipid profile, Fasting Blood Sugar (FBS) and HbA1c were estimated in all the subjects.

RESULTS

Apo B100/Apo A1 ratio and Lp(a) levels showed highly significant difference (p-value <0.001) between uncontrolled diabetics, controlled diabetics and healthy Controls. Apo B100/Apo A1 ratio and Lp(a) showed significant positive correlations with HbA1c (r= 0.494, p <0.0001) and with each other.

CONCLUSIONS

Apo B100/Apo A1 ratio and Lp(a) show a highly significant positive relationship with glucose tolerance of the patients as reflected in the HbA1c values. If proper glycemic control is maintained, the levels of Apo B100/Apo A1 ratio and Lp(a) can be controlled as reflected by the lower levels of these parameters observed in controlled diabetics in comparison to uncontrolled diabetics.

BACKGROUND

Lipid-lowering drugs are extensively used in primary care to reduce the risk of cardiovascular disease (CVD). Apart from high total cholesterol (TC), several other clinical-chemical variables are associated with the risk of CVD. Magnesium-pyridoxal-5'-phosphate-glutamate (MPPG) has been found to have a positive influence on TC levels and other clinical-chemical values in some selected populations.

OBJECTIVE

To assess, in a general practice (GP) setting, the efficacy and clinical effectiveness of MPPG in the treatment of clinical-chemical risk factors for CVD.

METHODS

Randomised double-blind, placebo-controlled, clinical trial, lasting 12 months.

METHODS

Adults (25-66 years) in an average Dutch village population with serum cholesterol levels between 7.0 mmol/l and 9.9 mmol/l.

METHODS

Subjects were assigned at random to treatment with MPPG (3 x 150 mg daily) or placebo. Clinical-chemical parameters were assessed at 1, 3, 6, 9 and 12 months (t1, t2, t3, t4, t5). Efficacy was measured at t2. Long-term effect (clinical effectiveness) was measured by combining the results at t2, t3, t4 and t5 (t2-5).

METHODS

TC (primary), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides, apolipoprotein-A1 (Apo-A1), apolipoprotein-B100 (Apo-B), fibrinogen and lipoprotein a [Lp(a), secondary].

RESULTS

No statistically significant differences in the efficacy and effectiveness of TC were found between the MPPG group and the placebo group. The same was demonstrated for the other clinical-chemical values, except for LDL-C (effectiveness, P = 0.04).

CONCLUSIONS

Efficacy and effectiveness of MPPG are too poor to be of relevance for application as a lipid-lowering drug in GP.

The serum concentrations of apolipoproteins C-III, B, and A-I were determined in children with type I diabetes mellitus to establish whether they correlated with the level of glycosylated hemoglobin (Hb A1) and to determine whether these values differ between diabetic children and a population of normal children. Triglyceride (TG), total cholesterol (TC), and apolipoprotein (Apo) levels were studied in 95 children with type I diabetes; 51 of the children were attending a diabetes clinic and 44 were attending a diabetes summer camp. The level of Hb A1 correlated with Apo C-III (P less than .001) and TC (P less than .001) values in the clinic group, but not with Apo A-I or TG levels in either group. The Apo C-III level was higher in both groups of diabetic children (8.0 +/- 0.5 and 9.5 +/- 0.4 mg/dl) (P less than .01) than in normal subjects (6.1 +/- 0.2 mg/dl). We conclude that the Apo C-III level tends to be higher in diabetics than in normal subjects, even in the normotriglyceridemic camp group. The Apo C-III level correlated with both the TC level and Hb A1, suggesting that Apo C-III determinations in type I diabetic patients may permit early identification of atherosclerotic risk.

OBJECTIVE

To determine the burden of atherogenic apolipoprotein particles in early-onset type 2 diabetes (T2D) compared to those with later-onset disease during statin treatment.

METHODS

Early and later-onset T2D was defined as current age below and above 40 years respectively. Conventional lipid profile, LDL, non-HDL cholesterol, apolipoprotein B and A1 were determined in those without cardiovascular disease treated with simvastatin to achieve LDL cholesterol <2 mmol/l.

RESULTS

Fifty subjects were recruited (early-onset n=24 and later-onset n=26). The mean age was 34.5 and 59.6 years and mean age of diagnosis was 29.1 and 49.1 years for early and later-onset T2D respectively. Obesity, dyslipidaemia, microalbuminuria, glycaemic control and diabetes complication burden were similar in both cohorts. Early-onset subjects received non-significantly higher simvastatin dose (37.5 vs. 31.9 mg daily, p=NS). On-treatment LDL cholesterol was similar in both cohorts (early vs. later-onset; 2.12 vs. 1.97 mmol/l, p=NS). Fasting triglyceride, non-HDL, apo B and B/A1 ratio were significantly higher in early-onset cohort. There was no difference in apo A1, HDL and total cholesterol/HDL ratio. Apo B level remained significantly higher among early-onset subjects after adjustment for insulin treatment. Lower current age and age of diagnosis were significant predictors of higher apo B level.

CONCLUSIONS

The burden of atherogenic apolipoprotein particles was greater in early-onset T2D despite adequate statin treatment indicating an adverse phenotype for vascular disease.

OBJECTIVE

To study the three cycles effect on primary dysmenorrhea of the monophasic 24/4 estradiol/nomegestrol acetate (E2/NOMAC) and of the 21/7 ethinyl-estradiol/chlormadinone acetate (EE/CMA) oral contraceptive. The tolerability and the effect of both preparations on metabolism and health-related quality of life were also evaluated.

METHODS

Prospective observational cohort study.

METHODS

Tertiary gynecologic center for pelvic pain.

METHODS

Subjects with primary dysmenorrhea requiring an oral contraceptive, who spontaneously selected either E2/NOMAC (n = 20) or EE/CMA (n = 20).

METHODS

Visual Analogue Scale (VAS) score for dysmenorrhea, Short Form-36 questionnaire for health-related quality of life, lipoproteins and days of menstrual bleeding (withdrawal bleeding during oral contraceptive).

RESULTS

Mean age and body mass index (BMI) were similar between the two groups. The final analysis was performed on 34 women, 15 in E2/NOMAC and 19 in EE/CMA group. Compliance with treatment was significantly higher with EE/CMA (100%) than E2/NOMAC (75%) (p = 0.02). Both treatments significantly (p < 0.0001) reduced VAS of primary dysmenorrhea, similarly (E2/NOMAC by a mean of 74.7%, EE/CMA by a mean of 78.4%; p = 0.973). Only E2/NOMAC significantly increased SF-36 score (p = 0.001), both in physical (p = 0.001) and mental domains (p = 0.004). The mean number of days of menstrual bleeding was significantly reduced in E2/NOMAC group (from 4.86 ± 1.20 d to 2.64 ± 1.59 d, p = 0.0005 versus baseline, p = 0.007 versus EE/CMA group). BMI did not vary in either group. E2/NOMAC did not change lipoproteins and apoproteins while EE/CMA increased total cholesterol (p = 0.0114), HDL-cholesterol (p = 0.0008), triglycerides (p = 0.002), apoprotein-A1 (Apo-A1; p = 0.0006) and apopoprotein-B (Apo-B; p = 0.008), decreasing LDL/HDL ratio (p = 0.024).

CONCLUSIONS

Both oral contraceptives reduced similarly primary dysmenorrhea, with E2/NOMAC also reducing withdrawal bleedings and being neutral on lipid metabolism.

BACKGROUND

Lipoprotein (a) (Lp(a)) is a risk marker for the development of atherosclerotic coronary heart disease. Growth hormone (GH) administration to GH-deficient (GHD) adults increases serum Lp(a) concentrations, and the levels of Lp(a) and GH are correlated in patients with acromegaly. Studies in rats have demonstrated differential effects of constant and intermittent GH patterns on levels of certain lipoproteins. The aim of the present studies was to describe the impact of intermittent and continuous patterns of GH delivery to GHD patients on serum levels of Lp(a) and other lipoproteins.

METHODS

In one study (A) 10 GHD patients received in random order a fixed GH dose intravenously as: (1) continuous infusion; (2) eight bolus injections, and (3) a combination of 1 and 2. Each study lasted 36 h and was preceded by at least 4 weeks without GH. In another study (B) 13 GHD patients received GH in random order as: (1) continuous subcutaneous (s.c.) infusion, and (2) daily s.c. injections in the evening for 1 month each. The patients were studied during steady-state conditions at the end of each treatment period.

RESULTS

In study A Lp(a) levels increased significantly following continuous (p < 0.05) and combined patterns (p < 0.02) of GH administration to GH-deprived GHD patients, whereas the increase after GH bolus injections alone was not significant (p = 0.14). In study B significantly higher (p < 0.05) serum levels of Lp(a) were obtained after continuous s.c. infusion as compared with daily s.c. injections of GH. Concentrations of the high-density lipoprotein (HDL) cholesterol were significantly lower (p < 0.02) after the continuous GH pattern. Similarly, the HDL fraction Apo A-1 tended to be lower with constant GH delivery (p = 0. 052). Serum levels of total cholesterol, triglyceride and Apo B were similar on the two occasions.

CONCLUSIONS

Short-term GH administration to GH-deprived GHD patients increased serum Lp(a), but only significantly with continuous delivery. During more prolonged GH exposure, constant s.c. infusion of GH resulted in slightly raised Lp(a) levels and reduced HDL and Apo A1 levels as compared with intermittently administered GH. The findings are consistent with the more effective induction of serum IGF-I levels after continuous patterns of GH delivery previously reported in GHD patients. Longer-term data are needed before conclusions with respect to the impact of the pattern of GH administration on, e.g., the risk of developing coronary heart disease can be drawn.

This study is expected to investigate the association of ATP/GTP binding protein-like 4 (AGBL4), LDL receptor related protein 8 (LRP8) and proprotein convertase subtilisin/kexin type 9 (PCSK9) gene single nucleotide variants (SNVs) with lipid metabolism in 2,552 individuals (Jing, 1,272 and Han, 1,280). We identified 12 mutations in this motif. The genotype and allele frequencies of these variants were different between the two populations. Multiple-locus linkage disequilibrium (LD) elucidated the detected sites are not statistically independent. Possible integrative haplotypes and gene-by-gene (G × G) interactions, comprising mutations of the AGBL4, LRP8 and PCSK9 associated with total cholesterol (TC, AGBL4 G-G-A, PCSK9 C-G-A-A and G-G-A-A-C-A-T-T-T-G-G-A), triglyceride (TG, AGBL4 G-G-A, LRP8 G-A-G-C-C, PCSK9 C-A-A-G, A-A-G-G-A-G-C-C-C-A-A-G and A-A-G-G-A-G-C-C-C-G-A-A), HDL cholesterol (HDL-C, AGBL4 A-A-G and A-A-G-A-A-G-T-C-C-A-A-G) and the apolipoprotein(Apo)A1/ApoB ratio (A1/B, PCSK9 C-A-A-G) in Jing minority. However, in the Hans, with TG (AGBL4 G-G-A, LRP8 G-A-G-C-C, PCSK9 C-A-A-G, A-A-G-G-A-G-C-C-C-A-A-G and A-A-G-G-A-G-C-C-C-G-A-A), HDL-C (LRP8 A-A-G-T-C), LDL-C (LRP8 A-A-G-T-C and A-A-G-A-A-G-T-C-C-A-A-G) and A1/B (LRP8 A-C-A-T-T and PCSK9 C-A-A-G). Association analysis based on haplotype clusters and G × G interactions probably increased power over single-locus tests especially for TG.

Lipid peroxidation was assessed by measuring the concentrations of thiobarbituric acid-reactive substances in plasma from 204 Type 2 diabetic patients, relative to 107 controls. The concentrations obtained in diabetic patients (3.08 +/- 0.37 mumol/l) were significantly higher than in controls (2.80 +/- 0.34 mumol/l) (p < 0.0001). Values were also significantly increased in patients with macroangiopathy and/or microangiopathy (3.17 +/- 0.41 mumol/l), relative to patients void of vascular complications (2.92 +/- 0.34 mumol/l) (p < 0.001). Elevated concentrations were independent of the type of vascular complication and their possible associations. In patients without vascular affection, thiobarbituric acid-reactive substances were in significantly higher concentrations in hypertensive (3.07 +/- 0.36 mumol/l) than in normotensive (2.87 +/- 0.29 mumol/l) (p < 0.01) patients. There was a correlation between these values and those of total cholesterol (r = 0.46, p < 0.0001) and triglyceride (r = 0.45, p < 0.0001). Statistical analysis by multivariate logistical regression revealed that among the independent factors (TBARS, APO A1, hypertension, age), thiobarbituric acid-reactive substances constituted the parameter most strongly linked to the existence of vascular complications. This study has evidenced a lipid peroxidation disorder in non insulin- dependent diabetes mellitus, more marked in patients with vascular affection. Thiobarbituric acid-reactive substances appear to be an independent marker of vascular complications in Type 2 diabetes.

Apolipoprotein H (apo H), also known as beta-2-glycoprotein I, has recently become of considerable interest in the field of haemostasis. Because of the possible involvement of apo H in lipid pathways, we wished to test the hypothesis that the serum concentration of apo H was related to serum lipids and other apolipoproteins in normal individuals. One hundred and twenty-three healthy young subjects (67 women and 56 men) aged 22.7 +/- 0.70 years (mean +/- SD) were recruited. Serum level of apo H was higher in male subjects that in age-matched female subjects (167.6 +/- 47.5 mg/l versus 148.8 +/- 30.5 mg/l; P < 0.04). Serum levels of apo H were significantly correlated with serum concentration of cholesterol, but only in female subjects (r = 0.28, P < 0.02). No significant correlations were found between serum levels of apo H and triglycerides, high-density lipoprotein cholesterol, apo A1, apo B or lipoprotein (a) in either of the sexes.

OBJECTIVE

Studies into the role of LRP1 (low-density lipoprotein receptor-related protein 1) in human lipid metabolism are scarce. Although it is known that a common variant in LRP1 (rs116133520) is significantly associated with HDL-C (high-density lipoprotein cholesterol), the mechanism underlying this observation is unclear. In this study, we set out to study the functional effects of 2 rare LRP1 variants identified in subjects with extremely low HDL-C levels.

UNASSIGNED

In 2 subjects with HDL-C below the first percentile for age and sex and moderately elevated triglycerides, we identified 2 rare variants in LRP1: p.Val3244Ile and p.Glu3983Asp. Both variants decrease LRP1 expression and stability. We show in a series of translational experiments that these variants culminate in reduced trafficking of ABCA1 (ATP-binding cassette A1) to the cell membrane. This is accompanied by an increase in cell surface expression of SR-B1 (scavenger receptor class B type 1). Combined these effects may contribute to low HDL-C levels in our study subjects. Supporting these findings, we provide epidemiological evidence that rs116133520 is associated with apo (apolipoprotein) A1 but not with apoB levels.

CONCLUSIONS

This study provides the first evidence that rare variants in LRP1 are associated with changes in human lipid metabolism. Specifically, this study shows that LRP1 may affect HDL metabolism by virtue of its effect on both ABCA1 and SR-B1.

Since an elevated serum concentration of lipoprotein(a) [Lp(a)] associated with a positive family history of premature myocardial infarction (PMI), would support the hypothesis that Lp(a) is a genetic risk factor for atherosclerosis, we measured serum levels in subjects from families with a history of PMI and compared them to those in a group of healthy control subjects. Twenty-five males (average age 39 +/- 16 years) and 9 females (average age 42 +/- 14 years) who had at least one blood relative affected by PMI were included in the study; 20 males (average age 41 +/- 11 years) and 10 females (average age 37 +/- 13 years) served as control subjects. Serum cholesterol, triglyceride, HDL-cholesterol, apo A1, apo B100 and Lp(a) concentrations were measured in both groups. The statistically significant higher prevalence of elevated Lp(a) levels >> 30 mg/dL) in the PMI group (p < 0.05) is attributable to the higher prevalence of PMI males with elevated Lp(a) levels. Pedigree studies disclosed a family distribution of coronary heart disease compatible with the hypothesis of a segregation of a dominant character for PMI risk. Because serum Lp(a) concentration is inherited with a Mendelian codominant pattern, we conclude that our data strongly support the hypothesis of a correlation between excess Lp(a) and coronary atherosclerosis.

OBJECTIVE

To explore the relationship of cathepsin L (CatL) with coronary heart disease (CHD), severity of coronary stenosis and risk factors of CHD.

METHODS

A total of 137 CHD patients and 48 controls were included in the study, to determined the serum levels of CatL, high sensitive C reactive protein (hs-CRP), fasting glucose (FBS), total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1(Apo-A1) and apolipoprotein B. All the subjects were invited for a coronary angiography, using the sum of the Gensini scores to assess the severity of coronary artery stenosis.

RESULTS

Serum CatL levels were significantly higher in CHD patients (5.63 +/= 0.12 microg/L) than non-CHD subjects (3.93 +/= 0.22 microg/L, P<0.01). CatL was an independent risk factor of CHD in Logistic regression analysis [Exp(B)=2.341, 95%CI 1.567 approximately 3.496, P<0.01]. Serum CatL levels were associated positively with the Gensini scores(r=0.228, P<0.01); In fact, CatL was an independent correlator of Gensini scores (P<0.05). CatL inversely associated with HDL-C (r=-0.228, P<0.01) and ApoA1(r=-0.187, P<0.05), and positively with FBS(r=0.161, P<0.05).

CONCLUSIONS

CatL is involved in the pathogenesis of CHD. Serum CatL levels could reflect the severity of coronary luminal narrowings. CatL might participate in glucose and lipid metabolic disorders.

Cholesterol is a major component of atherosclerotic plaques. Cholesterol accumulation within the arterial intima and atherosclerotic plaques is determined by the difference of cellular cholesterol synthesis and/or influx from apo B-containing lipoproteins and cholesterol efflux. In humans, apo A-1 Milano infusion has led to rapid regression of atherosclerosis in coronary arteries. We hypothesised that a multifunctional plasma delipidation process (PDP) would lead to rapid regression of experimental atherosclerosis and probably impact on adipose tissue lipids. In hyperlipidemic animals, the plasma concentrations of cholesterol, triglyceride and phospholipid were, respectively, 6-, 157-, and 18-fold higher than control animals, which consequently resulted in atherosclerosis. PDP consisted of delipidation of plasma with a mixture of butanol-diisopropyl ether (DIPE). PDP removed considerably more lipid from the hyperlipidemic animals than in normolipidemic animals. PDP treatment of hyperlipidemic animals markedly reduced intensity of lipid staining materials in the arterial wall and led to dramatic reduction of lipid in the adipose tissue. Five PDP treatments increased apolipoprotein A1 concentrations in all animals. Biochemical and hematological parameters were unaffected during PDP treatment. These results show that five PDP treatments led to marked reduction in avian atherosclerosis and removal of lipid from adipose tissue. PDP is a highly effective method for rapid regression of atherosclerosis.

Diabetes mellitus is frequently associated with lipid metabolism abnormalities. In the present study the lipid and apolipoprotein profiles have been compared in type II diabetic subjects with (n = 30) and without (n = 30) coronary heart disease (CHD). All subjects were studied after good metabolic control had been achieved. Significant differences in plasma lipids and apolipoproteins were seen in diabetic patients with CHD in comparison with diabetics without CHD. Patients with CHD presented higher total cholesterol, triglyceride, LDL-cholesterol, apo B, apo CII and apo CIII levels and total cholesterol/HDL-cholesterol and LDL-cholesterol HDL-cholesterol ratios and lower HDL-cholesterol values and apo A1/apo B ratio than the patients without CHD. The same findings were found in females; while male subjects with CHD had significantly increased total cholesterol, LDL-cholesterol and apo B levels and total cholesterol/HDL-cholesterol and LDL-cholesterol/HDL-cholesterol ratios and significantly decreased apo A1/apo B ratio compared with males without CHD. These findings support the concept that the apolipoprotein profile plays a remarkable role as risk factor for CHD in type II diabetes mellitus.

The influence of a very-low-calorie diet (VLCD) on lipid pattern is controversial. To evaluate the long-term effect of semistarvation on lipid patterns, a group of severely obese patients [aged 37 +/- 12 y, body mass index (BMI) 40.0 +/- 0.9] underwent a VLCD for 8 wk. Total cholesterol (TC), LDL cholesterol (LDL-C), and HDL cholesterol (HDL-C), triglycerides (TGs), apolipoproteins A1 (apo A1) and B (apo B) were analyzed every week. TC (6.07 +/- 0.23 vs 5.53 +/- 0.25 mmol/L, P less than 0.0008), HDL-C (mmol/L 1.26 +/- 0.06 vs 1.04 +/- 0.05 mmol/L, P less than 0.0001), TGs (1.46 +/- 0.19 vs 1.06 +/- 0.10 mmol/L, P less than 0.0008), and apo A1 (1.57 +/- 0.06 vs 1.32 +/- 0.06 g/L, P less than 0.0002) decreased, whereas LDL-C and apo B showed a biphasic behavior: they significantly fell during the first 3 wk, but during the last weeks returned to their initial values.

SPT2 chromatin protein domain containing 1 gene (SPTY2D1) is a candidate gene for dyslipidemia. The single nucleotide polymorphism (SNP) of rs7934205 near SPTY2D1 locus was ethnic- and sex-specific associated with serum lipid levels in our previous study. Whether SPTY2D1 rs17579600 SNP and several environmental factors are associated with serum lipid profiles is unknown. A total of 712 participants of Han and 689 unrelated individuals of Mulao were included. The genotype and allele frequencies of SPTY2D1 rs17579600 SNP were different between the Han and Mulao populations (TT, 74.3% vs. 55.7%; TC, 17.6% vs. 31.2%, CC, 8.1% vs. 13.1%, P = 0.028; T, 83.1% vs. 71.3%; C, 16.9% vs. 28.7%, P = 0.044), and between males and females in the both ethnic groups. The levels of serum apolipoprotein (Apo) A1 in Han, triglyceride (TG) in Mulao, and total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), ApoA1 and ApoB in Mulao males were difference among the genotypes. The C allele carriers had higher ApoA1 in Han, lower TG in Mulao, and lower TC, LDL-C and ApoB and higher ApoA1 in Mulao males than the C allele non-carriers. Serum lipid parameters were also associated with several environmental factors in both ethnic groups. The differences suggesting there may be a racial/ethnic- and/or sex-specific association between the SPTY2D1 rs17579600 SNP and serum lipid parameters in some ethnic groups.

In a prospective, randomized, cross-over study, 14 postmenopausal women completed 9 months of treatment with conjugated equine oestrogens, 1.25 mg daily. Seven women added dydrogesterone 20 mg daily for 12 days during months 2, 3 and 4, and then 10 mg daily for an identical time in months 5, 6 and 7. The other seven women added the two dydrogesterone doses in reverse sequence. No dydrogesterone was taken during months 8 and 9. Lipids and lipoproteins were measured before treatment and at the end of months 4, 7 and 9. Lipids were also estimated in an untreated (reference) group of eight postmenopausal women on two occasions 6 months apart; these showed significant changes in HDL2- and HDL3-cholesterol. In the treatment group, HDL-cholesterol and apolipoprotein (apo) A1 were significantly higher and LDL-cholesterol and apo B were significantly lower at months 4, 7 and 9 compared with baseline values. Triglyceride levels were increased significantly over baseline values, but remained within the normal range. No significant differences between the two dydrogesterone doses were observed on any lipid and lipoprotein fraction, nor were there any differences between the oestrogen-only and oestrogen/dydrogesterone treatment phases. Dydrogesterone appears to cause little, if any, lipid and lipoprotein changes and assessment in a larger population of postmenopausal women is warranted.

BACKGROUND

There is great need for new drugs to reduce cholesterol in those patients who have not achieved target levels on statins as well as those who are statin intolerant.

METHODS

In this review, the authors discuss the new antisense oligotide inhibitor of apo B synthesis, mipomersen; pro-protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and cholesterol ester transport protein (CETP) inhibitors. Furthermore, the authors discuss cholesterol absorption and chylomicron synthesis with an emphasis on microsomal triglyceride transfer protein (MTP) inhibitors, which inhibit very-low-density lipoprotein production in the liver and chylomicron inhibition in the intestine. Finally, the authors also discuss Apo A1- and adenosine triphosphate-binding cassette transporter A1 (ABCA1)-promoting drugs. A literature review was performed through PubMed using the terms atherosclerosis, hypercholesterolemia, Apo B inhibition, PSCK9, CETP inhibitors, MTP inhibitors, apo A1 mimetics and ABCA1.

CONCLUSIONS

So far, research suggests that PCSK9 inhibitors will be successful with mipomersen being used for those patients who do not respond well or who are still not at target. However, it is difficult to see where CETP inhibitors will fit in except with patients who have very low high-density lipoprotein. The MTP inhibitor lomitapide is currently only licensed for familial homozygous hypercholesterolemia but the intestinal inhibitors may have a future, particularly in familial combined hyperlipidemia. The future will be most exciting.

OBJECTIVE

To study the short-term efficacy, tolerability and safety of the treatment with gemfibrozil 600 mg twice daily or placebo in male patients with established atherosclerosis, with a lipid profile matching the 'high triglyceride-low high-density lipoprotein (HDL) cholesterol trait'.

METHODS

Double-blind randomized placebo controlled prospective trial.

METHODS

Amsterdam Lipid Research Clinic at the Academic Medical Centre of the University of Amsterdam and the Slotervaart Training Hospital affiliated to the University of Amsterdam, Amsterdam, the Netherlands.

METHODS

Thirty-five male patients, age 30-70, with established atherosclerosis and the high triglyceride-low HDL cholesterol trait.

METHODS

Plasma total cholesterol, triglycerides, lipoproteins, apolipoproteins A1 and B100, clinical and laboratory safety parameters.

RESULTS

Seventeen patients in the gemfibrozil group and 16 patients in the placebo group completed the study period. Compliance was considered adequate. Mean (+/- standard deviation) plasma HDL cholesterol levels increased 20.3% (+/- 12.22) from 0.82 to 0.99 mmol L-1 in the gemfibrozil group against 9.9% (+/- 18.31) from 0.79 to 0.87 mmol L-1 in the placebo group (P = 0.001). Mean plasma triglyceride level fell 49.5% (+/- 14.27) from 3.65 to 1.82 mmol L-1 in the gemfibrozil group against an increase of 13.6% (+/- 40.31) from 3.62 to 4.01 mmol L-1 in the placebo group (P < 0.001). Although plasma HDL cholesterol and triglyceride levels improved in all patients, normalization of these lipoproteins was only observed in approximately half of them. Plasma total and low-density lipoprotein (LDL) cholesterol levels, as well as plasma levels of apolipoprotein (apo) A1, B100 and lipoprotein [Lp(a)], did not show significant alterations compared to the placebo. All safety parameters were comparable between the two groups and remained within the reference limits. Gemfibrozil was well tolerated during treatment. Minor inconveniences were equally distributed between the two treatment groups.

CONCLUSIONS

Gemfibrozil is an effective and safe drug in patients with coronary heart disease (CHD) and the high triglyceride-low HDL cholesterol trait.

OBJECTIVE

To test the hypothesis that an acute increase in plasma homocysteine concentration (Hcy) produced by methionine loading is associated with an acute decrease in brachial artery blood flow measured by flow-mediated dilatation (FMD) using forearm plesthysmography.

METHODS

A double-blind, cross-over, placebo controlled design was used and FMD of the brachial artery, plasma Hcy, plasma methionine, total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, plasma triglyceride, oxidised LDL, apolipoproteins (Apo) A1 and B and C reactive protein (CRP) were measured between 12 and 20 hours after methionine loading or placebo.

RESULTS

Between 12 and 20 hours, after a methionine loading test, acute hyperhomocysteinaemia had no significant effect on mean FMD compared to placebo (57.08+/-6.18ml/100ml/min versus 63.46+/-5.87ml/100ml/min, p<0.5). The mean age of the eight subjects was 71.5+/-6.9 years. Twelve hours after methionine, mean triglyceride concentration was significantly increased by 23.0% compared to placebo (1.51+/-0.47mmol/l versus 1.23+/-0.44mmol/l, p<0.02).

CONCLUSIONS

In elderly volunteers, acute hyperhomocysteinaemia induced by methionine loading resulted in no significant late impairment of endothelial function although further investigation is recommended. Acute hyperhomocysteinaemia resulted in a significant increase in plasma triglyceride concentration.

We examined the acute and long-term effects of coronary artery bypass (CABG) surgery on serum lipid, lipoprotein and apolipoprotein levels. One series of 34 patients having CABG surgery was studied pre-operatively and for six weeks afterwards, and another 22 patients were investigated before and two years after CABG surgery. None of the patients studied received any lipid-lowering drug therapy or specific dietary advice. In both groups, pre-operative serum lipoprotein (a) (Lp(a)) and serum triglyceride concentrations were raised and serum high-density lipoprotein (HDL) cholesterol and apolipoprotein AI (apo AI) were low compared to healthy people. Acutely, there were profound decreases of 40-60% in the serum levels of cholesterol (p < 0.001), low-density lipoprotein cholesterol (p < 0.05), triglycerides (p < 0.01), Lp(a) (p < 0.05) and apolipoprotein B (apo B) (p < 0.05). There was a small decrease in serum apo A1 (p < 0.05), and serum HDL cholesterol showed no change. All these variables regained their pre-operative values within six weeks. Two years postoperatively, serum Lpa was 40% less than its pre-operative concentration (p < 0.001) and HDL cholesterol had increased (p < 0.001). Triglyceride levels decreased (p < 0.02) when beta-blockade was withdrawn. The long-term decrease in Lp(a) following surgery is unlikely to be due either to stopping beta-blockers or to life-style changes. Myocardial ischaemia relieved by the operation may have been partially responsible for its previously raised concentration.

Atherosclerotic manifestations are more common and precocious in diabetics than in the general population. Due to the increased cardiovascular risk, a primary or secondary (to diabetes mellitus) lipoprotein disorder in diabetics has to be carefully considered. 27 diabetics (15 NIDDM and 12 IDDM) with dyslipidemia (14 type IV, 8 type IIa and 5 type IIb) were divided in 3 groups and treated with 3 different hypolipemic drugs (Group A: pantethine 600 mg/day; Group B: acipimox 500 mg/day; Group C: bezafibrate 600 mg/day) to test their efficacy and acceptancy. Body weight, Hb A1-c, serum lipoproteins have been measured before and during the 6 months treatment. A significant variation of lipidemic pattern was observed in Group C: a decrease of cholesterol (-20%), triglycerides (-40%), LDL (-24.4%) and apo B (-26.8%) with an increase of HDL (+23.6%). Pantethine and acipimox were more effective on triglycerides (-37.7% and -23.3% respectively). Cardiovascular risk (CT tot/CT HDL) was significantly reduced with acipimox and normalized with bezafibrate.