Plasma levels of plant sterols and the risk of coronary artery disease: the prospective EPIC-Norfolk Population Study

Some studies have suggested that a modest increase of plant sterol levels is a risk factor for coronary artery disease (CAD). We studied the relationship between plant sterol levels and CAD risk in a prospective nested case-control study consisting of 373 cases and 758 controls. Sitosterol and campesterol concentrations did not differ between cases and controls [sitosterol, 0.21 vs. 0.21 mg/dl (P = 0.1); campesterol, 0.31 vs. 0.32 mg/dl (P = 0.5)]. The sitosterol-to-cholesterol ratio was significantly lower in cases than in controls (1.19 vs. 1.29 microg/mg; P = 0.008), whereas the campesterol-to-cholesterol ratio did not differ significantly (1.78 vs. 1.88 microg/mg; P = 0.1). Plant sterol concentrations correlated positively with cholesterol levels and inversely with body mass index and triglyceride and lathosterol concentrations. Among individuals in the highest tertile of the sitosterol concentration, the unadjusted odds ratio (OR) for future CAD was 0.75 [95% confidence interval (CI) = 0.56-1.01]. After adjustment for traditional risk factors, the OR was 0.79 (95% CI = 0.56-1.13). For the campesterol concentration, the unadjusted OR was 0.95 (95% CI = 0.71-1.29) and the adjusted OR was 0.97 (95% CI = 0.68-1.39). In this large prospective study, higher levels of plant sterols, at least in the physiological range, do not appear to be adversely related to CAD in apparently healthy individuals.     

Effect of apolipoprotein E genotype and saturated fat intake on plasma lipids and myocardial infarction in the Central Valley of Costa Rica

We assessed the effect of APOE polymorphisms -491 A/T, C112R (APOE*4), and R158C (APOE*2) and saturated fat intake on plasma lipid levels and risk of myocardial infarction (MI) in 1,927 case subjects and 1,927 population-based control subjects matched for age, sex, and residence, all living in the Central Valley of Costa Rica. A significant gene-diet interaction (p = 0.0157) was observed. High saturated fat intake was associated with a 49% increased risk of MI (OR = 1.49; 95% CI, 1.16-1.92) among wildtype subjects. In contrast, high saturated fat intake was associated with a 2.2-fold increased risk of MI among carriers of APOE*2 (OR = 3.17; 95% CI, 1.58-6.36) and with a 1.6-fold increase among carriers of the -491T and APOE*4 variants together (OR = 2.59; 95% CI, 1.38-4.87). Consistently, a high fat diet elicited a greater response in LDL cholesterol among carriers of APOE*2 (+ 17%) and APOE*4 (+ 14%) compared to noncarriers (+6%). The frequency of APOE variants was similar in case and control subjects, although APOE*4 homozygotes were at increased risk of MI compared to noncarriers (OR = 2.26; 95% CI, 1.03-4.98). This study supports the hypothesis that the APOE*2 and APOE*4 variants increase susceptibility to MI in the presence of high saturated fat and could explain inconsistent findings on the effects of these variants on MI in various populations.     

Association of circulating selenium concentration with dyslipidemia: Results from the NHANES

BackgroundObservational studies have suggested that selenium levels might associate with the risk of cardio-metabolic diseases, but how circulating selenium is related to dyslipidemia remains inconclusive.ObjectivesTo investigate the association of circulating selenium levels with lipid profiles and dyslipidemia among US adults.MethodsUsing the data collected from the National Health and Nutrition Examination Survey (NHANES 1999–2006), we performed multivariate logistic regression to examine the association of circulating selenium levels (in quartiles) with total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and atherogenic index (AI).ResultsWe included 2903 adults (49.3 % male) (average age: 61.9) for analysis. Circulating selenium had non-linear association with TC, LDL-C, HDL-C, and AI (all p < 0.05). When comparing with the lowest quartile, subjects with the highest quartile of circulating selenium (>147.00 μg/L) had the higher odds of elevated TG (OR: 1.75, 95% CI = 1.14, 2.68), TC (OR: 2.47, 95% CI = 1.62, 3.76), LDL-C (OR: 2.52, 95% CI = 1.60, 3.96), non-HDL-C (OR: 2.17, 95% CI = 1.41, 3.33), AI (OR: 1.20, 95% CI = 0.73, 1.97) and low-HDL-C (OR: 2.10, 95% CI = 1.19, 3.72). Similar patterns were observed in subgroup analysis.ConclusionsHigher circulating selenium levels had non-linear association with lipid profiles and the increased odds of dyslipidemia.     

Relations between particle size of HDL and LDL lipoproteins and cholesterol esterification rate

Particle size of low density (LDL) and high density (HDL) lipoproteins and cholesterol esterification rate in HDL plasma (FER(HDL)) are important independent predictors of coronary artery diseases (CAD). In this study we assessed the interrelations between these indicators and routinely examined plasma lipid parameters and plasma glucose concentrations. In 141 men, healthy volunteers, we examined plasma total cholesterol (TC), triglycerides (TG), HDL and LDL cholesterol (HDL-C, LDL-C) and HDL unesterified cholesterol (HDL-UC). Particle size distribution in HDL and LDL was assessed by gradient gel electrophoresis and FER(HDL) was estimated by radioassay. An effect of particle size and FER(HDL) on atherogenic indexes as the Log(TG/HDL-C) and TC/HDL-C was evaluated. Subjects in the study had plasma concentrations (mean +/- S.D.) of TC 5.2+/-0.9 mmol/l, HDL-C 1.2+/-0.3 mmol/l, TG 2.1+/-1.7 mmol/l, glucose 5+/-0.8 mmol/l. Relative concentration of HDL(2b) was 17.6+/-11.5 % and 14.6+/-11.8 % of HDL(3b,c). The mean diameter of LDL particles was 25.8+/-1.5 nm. The increase in FER(HDL) significantly correlated with the decrease in HDL(2b) and LDL particle size (r = -0.537 and -0.583, respectively, P<0.01) and the increase in HDL(3b,c) (0.473, P<0.01). Strong interrelations among TG and HDL-C or HDL-UC and FER(HDL) and particle size were found, but TC or LDL-C did not have such an effect. Atherogenic indexes Log(TG/HDL-C) and TC/HDL-C correlated with FER(HDL) (0.827 and 0.750, respectively, P<0.0001) and with HDL and LDL particle size.     

Influence of lipid metabolism disorders on venous thrombosis risk

Background: To investigate the influence of lipid metabolism disorders on the risk of deep vein thrombosis. Methods: A total of 200 subjects participated in the study, 100 of whom experienced DVT with or without PTE, and 100 healthy subjects representing the control group. We classified patients and controls in terms of serum concentrations of chylomicrons, LDL, IDL, VLDL, and HDL particles, as those with or without hyperlipoproteinemia and in terms of serum Lp (a) lipoprotein levels, as those with hyperLp (a) lipoproteinemia (serum Lp (a) values >0.3 g/L) and those without hyperLp (a) lipoproteinemia (serum Lp (a) values <0.3 g/L). Based on the modified and supplemented Fredrickson classification, participants with verified existences of hyperlipoproteinemia were classified into subgroups based on the type of hyperlipoproteinemia. Unconditional logistic regression was used to calculate ORs with 95% CIS as a measure of the relative risks for venous thrombosis in participants with hyperlipoproteinemia compared with those without hyperlipoproteinemia. The analysis was adjusted for all potential confounders (age, sex, obesity) related to the functionality of the lipid metabolism, and at the same time, may have an impact on the risk of venous thrombosis. Results: The results of the comparison of the mean values of individual lipid status parameters between the patient group and the control group clearly indicate higher concentrations of total cholesterol (5.93 mmol/L vs. 5.52 mmol/L), total triglycerides (1.58 mmol/L vs. 1.50 mmol/L), and LDL-cholesterol (3.83 mmol/L vs. 3.44 mmol/L) in the patient group relative to the control group, with a statistically significant difference observed only in the case of LDL-cholesterol concentrations. We have found that type IIa hyperlipoproteinemia is associated with a nearly double increased risk for deep vein thrombosis (OR 1.99; Cl 1.01-3.90), while type IIb, IV, or hyperLp (a) lipoproteinemia did not influence the risk (OR 1.22; 95% Cl 0.79-1.84; OR 0.89; 95% Cl 0.52-1.54 OR 1.85; 95% CI 0.84-4.04). Conclusions: Hypercholesterolemia doubles the risk of deep vein thrombosis development.     

Modification of the coronary artery disease risk associated with the presence of traditional risk factors by insertion/deletion polymorphism of the ACE gene

Cigarette smoking, hypercholesterolemia, and obesity influence the renin-angiotensin system (RAS) functions including an increased synthesis of the angiotensin I converting enzyme (ACE). Thus in the present work we explore the interactions of the ACE gene insertion/deletion (I/D) polymorphism and traditional risk factors. The study cohort included 341 subjects composed of 172 patients with angiographically confirmed CAD and 169 blood donors without a history of cardiovascular diseases. The I/D polymorphism was genotyped using polymerase chain reaction (PCR) methodology. To determine the interactions between the ACE genotypes and traditional risk factors the epidemiologic approach was used (4 x 2 tables and the synergy measures). The frequency of the DD genotype was significantly higher in patients than in controls (33.7% versus 21.3%, odds ratio [OR] = 1.88, 95% CI; 1.13-3.15, p = 0.010), but greater differences were found in males (35.7% versus 20.5%, OR = 2.15, 95% CI: 1.14-4.04, p = 0.010). We found a synergy of the DD genotype with smoking (SI = 1.88, SIM = 1.22), total cholesterol > or =5 mmol/l (SI = 2.12, SIM = 1.31) and elevated low density lipoprotein (LDL) cholesterol level (> or =3 mmol/l) (SI = 1.78, SIM = 1.14). The presence of the D allele (DD + ID subjects) also increased the risk of coronary artery disease (CAD) associated with the presence of elevated total cholesterol and LDL cholesterol (SI = 1.69, SIM = 1.18, in both cases), elevated level (> or =1.7 mmol/l) of triacylglycerols (SI = 1.81, SIM = 1.18) and overweight/obesity (SI = 4.25, SIM = 2.36). In each case the estimated CAD risk was greater than that predicted by assuming the additivity of effects (the risk increased from 69% for the D allele - total cholesterol interaction to 325% for the D allele - overweight/obesity). The statistical significance was also confirmed by a multiplicative model of synergy. The DD genotype/D allele of the ACE gene increases the risk of CAD associated with the presence of traditional risk factors.     

Apolipoprotein B and non-high density lipoprotein cholesterol and the risk of coronary heart disease in Chinese

The aim of our study was to compare apolipoprotein B (apoB), non-high density lipoprotein cholesterol (nonHDL-C), low density lipoprotein cholesterol (LDL-C), and other lipid markers as predictors of coronary heart disease (CHD) in Chinese. Overall, 122 individuals developed CHD during a median 13.6 years of follow-up in 3,568 adult participants from a community-based cohort. The multivariate relative risk of CHD in the highest quintile compared with the lowest quintile was 2.74 [95% confidence interval (CI), 1.45-5.19] for apoB, 1.98 (95% CI, 1.00-3.92) for nonHDL-C, and 1.86 (95% CI, 1.00-3.49) for LDL-C (all tests for trend, P < 0.05). ApoB also had the highest receiver operator characteristic curve area (0.63; 95% CI, 0.58-0.68) in predicting CHD. When apoB and nonHDL-C were mutually adjusted, only apoB was predictive; the relative risk was 2.80 (95% CI, 1.31-5.96; P = 0.001) compared with 1.09 (95% CI, 0.49-2.40; P = 0.75) for nonHDL-C. Compared with the lowest risk, participants with the highest apoB and total cholesterol/HDL-C had a 3-fold increased risk of developing CHD (relative risk = 3.21; 95% CI, 1.45-7.14). These data provide strong evidence that apoB concentration was a better predictor of CHD than other lipid markers in Chinese.     

Maternal vitamin B-6 and folate status and risk of oral cleft birth defects in the Philippines

BACKGROUND: Vitamin deficiencies induce oral clefts in animal experiments, but the role of specific nutrients in human oral clefts is uncertain. METHODS: Associations between maternal vitamin B-6 and folate status and risk of nonsyndromic cleft lip, with or without cleft palate (CL/P), were examined in case-control studies at two sites in the Philippines--Negros Occidental and Davao. Cases were mothers of affected children and control mothers were those who had no children with oral clefts. RESULTS: The risk of having a CL/P-affected child increased with increasing tertile of vitamin B-6 deficiency in both Negros Occidental and Davao (odds ratios [ORs] and 95% confidence intervals [CIs] for sites combined = 1.0 [reference], OR, 2.94; 95% CI, 1.51-5.73; OR, 4.98; 95% CI, 2.56-9.67). Poor B-6 status had a stronger association with CL/P among mothers with lower versus higher plasma folate levels. Increasing tertiles of plasma folate were marginally associated with an increased risk of clefts in both sites combined (1.0 [reference]; OR, 1.58; 95% CI, 0.93-2.68; OR, 1.59; 95% CI, 0.94-2.70). Increasing tertiles of erythrocyte folate were associated with a decreased risk of CL/P in Negros Occidental (1.0 [reference]; OR, 0.34; 95% CI, 0.13-0.90; OR, 0.46; 95% CI, 0.20-1.09) and an increased risk in Davao (1.0 [reference]; OR, 1.23; 95% CI, 0.54-2.81; OR, 4.85; 95% CI, 2.24-10.50). The inconsistent associations between folate status and CL/P risk appeared to be a result of statistical interaction between folate, vitamin B-6, and case-control status that produced different results in study areas of higher versus lower prevalence of vitamin B-6 deficiency. CONCLUSIONS: Poor maternal vitamin B-6 status was consistently associated with an increased risk of CL/P at two sites in the Philippines. Folate-CL/P associations were inconsistent and may be related to the vitamin B-6 status or other characteristics of the populations under study.     

HbA1c Alone Is a Poor Indicator of Cardiometabolic Risk in Middle-Aged Subjects with Pre-Diabetes but Is Suitable for Type 2 Diabetes Diagnosis: A Cross-Sectional Study

Objectives

Glycated haemoglobin A_1c (HbA_1c) measurement is recommended as an alternative to fasting plasma glucose (FPG) for the diagnosis of pre-diabetes and type 2 diabetes. However, evidence suggests discordance between HbA_1c and FPG. In this study we examine a range of metabolic risk features, pro-inflammatory cytokines, acute-phase response proteins, coagulation factors and white blood cell counts to determine which assay more accurately identifies individuals at increased cardiometabolic risk.

Materials and Methods

This was a cross-sectional study involving a random sample of 2,047 men and women aged 46-73 years. Binary and multinomial logistic regression were employed to examine risk feature associations with pre-diabetes [either HbA_1c levels 5.7-6.4% (39-46 mmol/mol) or impaired FPG levels 5.6-6.9 mmol/l] and type 2 diabetes [either HbA_1c levels >6.5% (>48 mmol/mol) or FPG levels >7.0 mmol/l]. Receiver operating characteristic curve analysis was used to evaluate the ability of HbA_1c to discriminate pre-diabetes and diabetes defined by FPG.

Results

Stronger associations with diabetes-related phenotypes were observed in pre-diabetic subjects diagnosed by FPG compared to those detected by HbA_1c. Individuals with type 2 diabetes exhibited cardiometabolic profiles that were broadly similar according to diagnosis by either assay. Pre-diabetic participants classified by both assays displayed a more pro-inflammatory, pro-atherogenic, hypertensive and insulin resistant profile. Odds ratios of having three or more metabolic syndrome features were also noticeably increased (OR: 4.0, 95% CI: 2.8-5.8) when compared to subjects diagnosed by either HbA_1c (OR: 1.4, 95% CI: 1.2-1.8) or FPG (OR: 3.0, 95% CI: 1.7-5.1) separately.

Conclusions

In middle-aged Caucasian-Europeans, HbA_1c alone is a poor indicator of cardiometabolic risk but is suitable for diagnosing diabetes. Combined use of HbA_1c and FPG may be of additional benefit for detecting individuals at highest odds of type 2 diabetes development.     

Both Serum Apolipoprotein B and the Apolipoprotein B/Apolipoprotein A-I Ratio Are Associated with Carotid Intima-Media Thickness

Background

Previous studies indicated that apolipoprotein measurements predicted cardiovascular disease (CVD) risk; however, associations between apolipoproteins and carotid intima-media thickness (CIMT) were less explored.

Methodology and Principal Findings

The cross-sectional study included 6069 participants aged 40 years or older with NGT from Shanghai, China. Serum fasting traditional lipids (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C] and triglycerides [TG]), apoA-I and apoB were assessed. A high-resolution B-mode ultrasonography was performed to measure CIMT. We found CIMT increased progressively across the quartiles of serum apoB (p for trend <0.0001). In logistic regression, concentrations of apoB (odds ratio [OR] 1.27, 95% confidence interval [CI] 1.18–1.36), TC (OR 1.23, 95% CI 1.14–1.32), LDL-C (OR 1.25, 95% CI 1.16–1.34) and TG (OR 1.11, 95% CI 1.04–1.20) were significantly related to elevated CIMT after adjusted for age and sex. Meanwhile, the apoB/apoA-I ratio (OR 1.25, 95% CI 1.17–1.34) related to elevated CIMT. ApoB (OR 1.23, 95% CI 1.00–1.51) and the apoB/apoA-I ratio (OR 1.19, 95% CI 1.04–1.36) remained significantly associated with elevated CIMT, after adjusted for the traditional CVD risk factors including traditional lipids.

Conclusions and Significance

There were significant associations between serum apoB, the apoB/apoA-I ratio and elevated CIMT. Serum apoB and the apoB/apoA-I ratio might be independent predictors of early atherosclerosis in NGT.     

Plasma protein carbonyl levels and breast cancer risk

To study the role of oxidative stress in breast cancer risk, we analysed plasma levels of protein carbonyls in 1050 cases and 1107 controls. We found a statistically significant trend in breast cancer risk in relation to increasing quartiles of plasma protein carbonyl levels (OR = 1.2, 95% CI = 0.9-1.5; OR = 1.5, 95% CI = 1.2-2.0; OR = 1.6, 95% CI = 1.2-2.1, for the 2(nd), 3(rd) and 4(th) quartile relative to the lowest quartile, respectively, P for trend = 0.0001). The increase in risk was similar for younger (<50 years) and older women, more pronounced among women with higher physical activity levels (0.7 hrs/week for 4(th) quartile versus lowest quartile OR = 2.0, 95% CI = 1.4-3.0), higher alcohol consumption (> or = 15 grams/day for 4(th) quartile versus lowest quartile OR = 2.3, 95% CI = 1.1-4.7), and hormone replacement therapy use (HRT, OR = 2.6, 95% CI = 1.6-4.4 for 4(th) quartile versus lowest quartile). The multiplicative interaction terms were statistically significant only for physical activity and HRT. The positive association between plasma protein carbonyl levels and breast cancer risk was also observed when the analysis was restricted to women who had not received chemotherapy or radiation therapy prior to blood collection. Among controls, oxidized protein levels significantly increased with cigarette smoking and higher fruit and vegetable consumption, and decreased with alcohol consumption >30 grams per day. Women with higher levels of plasma protein carbonyl and urinary 15F(2t)-isoprostane had an 80% increase in breast cancer risk (OR = 1.8, 95% CI = 1.2-2.6) compared to women with levels below the median for both markers of oxidative stress. In summary, our results suggest that increased plasma protein carbonyl levels may be associated with breast cancer risk.     

Serum cholesterol concentration and death from suicide in men: Paris prospective study I.

OBJECTIVE: To investigate whether low serum cholesterol concentration or changing serum cholesterol concentration is associated with risk of suicide in men. DESIGN: Cohort study with annual repeat measurements of serum cholesterol concentration (for up to four years). SETTING: Paris, France. SUBJECTS: 6393 working men, aged 43-52 in 1967-72, who had at least three measurements of serum cholesterol concentration. MAIN OUTCOME MEASURES: Individual change over time in serum cholesterol concentration (estimated using within person linear regression method); death from suicide during average of 17 years'' follow up after last examination. RESULTS: 32 men committed suicide during follow up. After adjustment for age and other factors, relative risk of suicide for men with low average serum cholesterol concentration (< 4.78 mmol/l) compared with those with average serum cholesterol concentration of 4.78-6.21 mmol/l was 3.16 (95% confidence interval 1.38 to 7.22, P = 0.007). Men whose serum cholesterol concentration decreased by more than 0.13 mmol/l a year had multivariate adjusted relative risk of 2.17 (0.97 to 4.84, P = 0.056) compared with those whose cholesterol remained stable (change of < or = 0.13 mmol/l a year). CONCLUSION: Both low serum cholesterol concentration and declining cholesterol concentration were associated with increased risk of death from suicide in men. Although there is some evidence in favour of a concomitant rather than a causal effect for interpreting these associations, long term surveillance of subjects included in trials of lipid lowering treatments seems warranted.     

Association of excision repair cross-complimentary group 1 gene polymorphisms with breast and ovarian cancer susceptibility

The role of excision repair cross-complimentary group 1 (ERCC1) gene polymorphisms in breast and ovarian cancer development has long been controversial and existing data were inconsistent. Here, we conducted a comprehensive meta-analysis to better clarify the association. Case-control studies published from December 2008 to November 2018 were assessed. The statistical analyses of the pooled odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were calculated. Fifteen articles with 24 case-control studies and 3 ERCC1 polymorphisms were enrolled. A total of 20 923 participants including 9896 cases and 11 027 controls were analyzed. The results showed that C to T variation in the ERCC1 rs11615 (C/T) polymorphisms was correlated with breast cancer susceptibility (T vs C: OR = 1.19, 95% CI = 1.02-1.38; TT + CT vs CC: OR = 1.24, 95% CI = 1.12-1.36). ERCC1 rs3212986 (C/A) polymorphisms posed an increased risk for breast and ovarian cancer as whole (A vs C: OR = 1.12, 95% CI = 1.01-1.25; AA + CA vs CC: OR = 1.11, 95% CI = 1.02-1.22), and presented especially higher risk for ovarian cancer (A vs C: OR = 1.31, 95% CI = 1.05-1.63; AA vs CA + CC: OR = 1.66, 95% CI = 1.12-2.47; AA vs CC: OR = 1.72, 95% CI = 1.12-2.64). Meanwhile, neither overall group analyses nor stratified analyses displayed any association of ERCC1 rs2298881 (A/C) polymorphisms in breast and ovarian cancer susceptibility. This meta-analysis suggested that ERCC1 rs11615 (C/T) polymorphisms were associated with breast cancer susceptibility and rs3212986 (C/A) polymorphisms were especially correlated with ovarian cancer risk. More case-control studies with well-adjusted data and diverse populations are essential for validation of our conclusion.     

The Role of Genetic Risk Score in Predicting the Risk of Hypertension in the Korean population: Korean Genome and Epidemiology Study

Hypertension is regarded as a multifactorial disease with a modest contribution of genetic factors and strongly affected by environmental factors. Recent genome-wide association studies have identified specific loci associated with high blood pressure (BP) and hypertension. This study aimed to examine the association between the genetic risk score (GRS), a linear function of multiple single nucleotide polymorphisms (SNPs) associated with hypertension, and high BP and prevalent hypertension at baseline examination and to evaluate the efficacy of the GRS for predicting incident hypertension with longitudinal data in Korean subjects. Data for 8,556 participants, aged 40 to 69, in a community-based cohort study were analyzed. Unweighted GRS (cGRS) and weighted GRS (wGRS) were constructed from 4 SNPs related to high BP or hypertension in previous genome-wide association and its replication studies for the Korean middle-aged population. Cross-sectional analysis (n=8,556) revealed that cGRS was significantly associated with prevalent hypertension (odds ratio=1.15 per risk allele; 95%CI, 1.09-1.20). Additionally, the odds ratios (ORs) of prevalent hypertension for those who in medium and the highest tertile compared with those who in the lowest tertile of wGRS were 1.31 (95% CI, 1.15-1.50) and 1.59 (95%CI, 1.38-1.82), respectively. In a longitudinal analysis (n=5,632), participants in the highest tertile of wGRS had a 1.22-fold (OR=1.22, 95%CI, 1.02‒1.46) greater risk of incident hypertension relative to those in the lowest tertile, after adjusting for a number of confounding factors. However, wGRS topped with traditional risk factors had no significant effect on discrimination ability (c-statistics with and without wGRS were 0.811 and 0.810, P=0.1057). But, reclassification analysis showed that the addition of GRS to the model with conventional risk factors led to about 9% significant increment in category-free net reclassification improvement. GRSs based on 4 SNPs were independently associated with hypertension and may provide a statistically significant improvement over the existing model for prediction of incident hypertension.     

Prevalence and associated factors of dyslipidemia in the adult Chinese population

To determine the prevalence, associated factors, awareness and control of dyslipidemia in Chinese living in Greater Beijing, we measured the serum cholesterol concentration in 3251 Chinese adults (age: 45 to 89 years) as participants of the population-based Beijing Eye Study 2006. Additional information on treatment of dyslipidemia was obtained using a standard questionnaire. The mean concentrations of total, HDL cholesterol, LDL cholesterol and triglycerides were 4.92±1.01 mmol/L, 1.61±0.36 mmol/L, 2.88±0.85 mmol/L, and 1.76±1.29 mmol/L, respectively. Prevalence of dyslipidemia was 56.1±0.9%%. Presence of dyslipidemia was significantly associated with increasing age (odds ratio (OR):1.02; 95% confidence interval (CI): 1.01, 1.03), female gender (OR:1.51; 95%CI: 1.25, 1.83), urban region (OR:1.82; 95%CI: 1.30, 2.55), body mass index (OR:1.13; 95%CI: 1.10, 1.15), income (OR:1.11; 95%CI:1.02, 1.21), blood glucose concentration (OR:1.10; 95%CI:1.05, 1.16), diastolic blood pressure (OR:1.02; 95%CI: 1.01, 1.03), and smoking (OR:1.23; 1.01, 1.51). Among those who had dyslipidemia, the proportion of subjects who were aware, treated and controlled was 50.9%, 23.8%, and 39.91%, respectively. The awareness rate was associated with urban region (P = 0.001; OR: 6.50), body mass index (P = 0.001; OR:1.06), and income (P = 0.02; OR:1.14). The data suggest that dyslipidemia may be present in about 56% of the population aged 45+ years in Greater Beijing. Factors likely associated with dyslipidemia were higher age, female gender, urban region, higher body mass index, higher income, higher blood concentration of glucose, higher diastolic blood pressure, and smoking. In the examined study population, treatment rate was 24% with about 60% of the treated subjects still having uncontrolled dyslipidemia.     

Serum Lipids and Breast Cancer Risk: A Meta-Analysis of Prospective Cohort Studies

Purpose

Epidemiologic studies exploring causal associations between serum lipids and breast cancer risk have reported contradictory results. We conducted a meta-analysis of prospective cohort studies to evaluate these associations.

Methods

Relevant studies were identified by searching PubMed and EMBASE through April 2015. We included prospective cohort studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the associations of specific lipid components (i.e., total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], and triglycerides [TG]) with breast cancer risk. Either a fixed- or a random-effects model was used to calculate pooled RRs.

Results

Fifteen prospective cohort studies involving 1,189,635 participants and 23,369 breast cancer cases were included in the meta-analysis. The pooled RRs of breast cancer for the highest versus lowest categories were 0.96 (95% CI: 0.86–1.07) for TC, 0.92 (95% CI: 0.73–1.16) for HDL-C, 0.90 (95% CI: 0.77–1.06) for LDL-C, and 0.93 (95% CI: 0.86–1.00) for TG. Notably, for HDL-C, a significant reduction of breast cancer risk was observed among postmenopausal women (RR = 0.77, 95% CI: 0.64–0.93) but not among premenopausal women. Similar trends of the associations were observed in the dose-response analysis.

Conclusions

Our findings suggest that serum levels of TG but not TC and LDL-C may be inversely associated with breast cancer risk. Serum HDL-C may also protect against breast carcinogenesis among postmenopausal women.     

Two polymorphisms of the FVII gene and their impact on the risk of myocardial infarction in poles under 45 years of age

High levels of coagulation factor VII (FVII) in plasma have been associated with the increased risk of myocardial infarction (MI) in some studies. Both environmental and genetic factors are responsible for different levels of FVII in plasma. In the FVII gene there are two common polymorphisms (−323A1/A2 and IVS7) which are related to the level of FVII. The purpose of this study was to evaluate the influence of these polymorphisms on the risk of acute myocardial infarction in Poles under 45 years of age. We performed a case-control study of 266 patients with the history of MI. All patients had the first incidence of MI before 45 years of age. The control group consisted of 137 healthy individuals older than 45 years. Carriers of the A2 allele (−323A1/A2 polymorphism) have a lower risk of MI than non-carriers (OR = 0.40, 95% CI = 0.20−0.80). The IVS7 polymorphism was shown not to be related to MI in this study. Our findings suggest that the −323A1/A2 polymorphism of the FVII gene is related to the risk of MI in Polish individuals. We pointed that plasma cholesterol (OR = 1.11, 95% CI = 1.03−1.18), arterial hypertension (OR = 3.84, 95% CI = 1.99−7.43) and family history (OR = 2.72, 95% CI = 1.57−4.73) are significant predictors of acute myocardial infarction.     

Alcohol consumption and its relation to cardiovascular risk factors in British women.

OBJECTIVE--To examine the relation between alcohol consumption and risk factors for coronary heart disease in women. DESIGN--Cross sectional study of a stratified random sample of the population grouped into five categories of habitual alcohol consumption. SETTING--People registered with general practitioners at two large health centres in east Bristol, England. SUBJECTS--1048 women aged 25-69 years. MAIN OUTCOME MEASURES--Fasting plasma concentrations of insulin, total cholesterol, total triglycerides, and high density lipoprotein cholesterol, including its subfractions HDL2 and HDL3, and body mass index. RESULTS--Compared with non-drinkers women consuming a moderate amount of alcohol (1-20 g/day) had lower plasma concentrations of triglycerides, by 0.19 mmol/l (95% confidence interval 0.07 to 0.35); cholesterol, by 0.4 mmol/l (0.19 to 0.61); and insulin, by 1.4 mU/l (0.43 to 1.97) and a lower body mass index, by 1.2 kg/m2 (0.43 to 1.97). They also had higher concentrations of high density lipoprotein cholesterol, by 0.09 mmol/l (0.03 to 0.15); HDL2 cholesterol by 0.05 mmol/l (-0.02 to 0.10) and HDL3 cholesterol, by 0.06 mmol/l (0.06 to 0.11). All these were independent of body mass index, smoking habits, and taking oral contraceptives. CONCLUSIONS--Moderate alcohol consumption is associated with lower levels of cardiovascular risk factors in women. Insulin may have a central role.     

Gender differences in plasma levels of lipoprotein (a) in patients with angiographically proven coronary artery disease

The objective of the study was to assess the association between plasma levels of lipoprotein(a) [Lp(a)] and the presence of angiographically defined coronary artery disease (aCAD). Patients (346 men and 184 women) undergoing selective coronary angiography (SCA) were classified into groups with positive [aCAD(+)] and negative [aCAD(-)] findings and their age, body mass index (BMI), waist circumference, blood pressure, smoking, plasma total, LDL-, HDL-cholesterol (TC, LDL-C, HDL-C), triglycerides (TG), apolipoprotein B (apoB), Log(TG/HDL-C) and TC/HDL-C were determined. Concentration of plasma Lp(a) was estimated using the commercial solid phase two-side immunoradiometric assay of apolipoprotein apo(a). The plasma Lp(a) was significantly higher in both women and men with aCAD(+) compared to those with aCAD(-). While there was no significant difference in the Lp(a) level between men and women with aCAD(-) (median 138 vs. 145 units/l), the women with aCAD(+) had almost twice as high Lp(a) levels as men (median 442 vs. 274 units/l, p<0.001). Women with aCAD(+) had also significantly lower HDL cholesterol levels (1.09 vs. 1.20 mmol/l, p<0.05), higher triglycerides (1.82 vs. 1.46 mmol/l, p<0.05) and Log(TG/HDL-C) than women with aCAD(-). The differences in Lp(a) between positive and negative findings remained highly significant (p<0.001 in women, p<0.05 in men) after the adjustment for age, plasma HDL- and LDL-cholesterol and triglycerides in logistic regression analyses. In logistic regression model the Lp(a) and Log(TG/HDL-C) and smoking in women but smoking and age in men were the most powerful predictors of positive aCAD findings. Our findings suggest that Lp(a) is more strongly associated with aCAD+ in women than in men.     

Compound heterozygosity at the sphingomyelin phosphodiesterase-1 (SMPD1) gene is associated with low HDL cholesterol

Type A and B forms of Niemann-Pick disease (NPD) are lipid storage disorders caused by deficient activity of the enzyme acid sphingomyelinase (aSMase) and the resulting accumulation of sphingomyelin in tissues. In the present study, we investigated two family members who had been diagnosed with Type B NPD and who had a severe decrease in plasma high density lipoprotein cholesterol (HDL-C). The proband (a 48-year-old male) had an HDL-C of 0.30 mmol/l (12 mg/dl) and his sister had values of 0.45 mmol/l (17 mg/dl) with severe premature coronary artery disease (CAD). Hypertriglyceridemia was found in both cases. aSMase activity measured in skin fibroblasts appeared markedly depressed. The SMPD1 gene, coding for aSMase, was sequenced in affected subjects and all family members. Compound heterozygosity (DeltaR608 and R441X) was identified in both affected patients. Carriers of the DeltaR608 mutation tended to have moderately to severe decreased HDL-C levels, whereas carriers of the R441X mutation, although present only in young subjects (<20 years of age) had normal HDL-C levels. To investigate the cause of the low HDL-C level in these patients, we studied apoA-I-mediated cellular cholesterol efflux in fibroblasts. Unlike patients with Tangier disease, cholesterol efflux was found to be normal under the experimental conditions used in the present study. On the other hand, we observed a significant increase in the free cholesterol:esterified cholesterol ratio in HDL fraction from these patients and a decrease in endogenous lecithin-cholesterol acyltransferase (LCAT) activity, as determined by the fractional esterification rate. Taken together, these results suggest that (1) compound heterozygosity at the SMPD1 gene causes a severe decrease in aSMase activity and in HDL-C and increases the risk of CAD, (2) this lipoprotein abnormality is not attributable to defective cellular cholesterol efflux, (3) abnormal HDL composition might cause a decrease in LCAT activity and a lack of HDL maturation.