Background

Increased levels of C-reactive protein (CRP), common in aging populations, are associated with higher risk for chronic diseases, including diabetes and coronary heart disease. The aim of this study was to investigate associations between lifestyle factors and high CRP among middleaged men living in Shanghai, China.

Recent studies have suggested that CRP may interfere with insulin signaling in skeletal muscle and endothelial cells. The aim of this study was to determine whether highly purified CRP increased the rate of glucose appearance in primary hepatocytes in the absence or presence of insulin. Primary rat hepatocytes were provided glucose-free media containing 10 mM lactate, 1mM pyruvate, 0, 1 or 10 nM insulin, and 0 or 10 μg/ml of purified CRP for 6h. Purified CRP did not increase glucose release in the absence of insulin and did not reduce the ability of insulin to suppress glucose release.

Background

Evaluation of metabolic syndrome (MetS) characteristics across an age spectrum from childhood to adulthood has been limited by a lack of consistent MetS criteria for children and adults and by a lack of adjustment for environmental factors. We used the pediatric and adult International Diabetes Federation (IDF) criteria to determine whether gender- and race-specific differences in MetS and its components are present in adolescents as in adults after adjustment for socioeconomic status (SES) and lifestyle factors.

Methods

Waist circumference, blood pressure, triglycerides, HDL cholesterol, and fasting glucose measures were obtained from 3,100 adolescent (12-19y) and 3,419 adult (20-69y) non-Hispanic white, non-Hispanic black, and Mexican-American participants of the 1999-2006 National Health and Nutrition Examination Surveys. We compared odds of having MetS and its components across racial/ethnic groups by age group, while adjusting for income, education, physical activity and diet quality.

Results

After adjusting for possible confounding influences of SES and lifestyle, non-Hispanic-black adolescent males exhibited a lower odds of MetS and multiple components (abdominal obesity, hypertriglyceridemia, low HDL, hyperglycemia) compared to non-Hispanic-white and Mexican-American adolescents. Compared to non-Hispanic white adolescent males, Mexican-American adolescent males had less hypertension. There were no differences in MetS prevalence among adolescent females, though non-Hispanic-black girls exhibited less hypertriglyceridemia.

Conclusion

Racial/ethnicity-specific differences in MetS and its components are present in both adolescence and adulthood, even after adjusting for environmental factors. These data help strengthen arguments for developing racial/ethnic-specific MetS criteria to better identify individuals at risk for future cardiovascular disease.

Background and Aims

Previously, we found significantly higher serum leptin in Japanese-Americans in Hawaii than Japanese in Japan. We investigated whether differences in dietary and other lifestyle factors explain higher serum leptin concentrations in Japanese living a Western lifestyle in Hawaii compared with Japanese in Japan.

Methods and Results

Serum leptin and nutrient intakes were examined by standardized methods in men and women ages 40 to 59 years from two population samples, one Japanese-American in Hawaii (88 men, 94 women), the other Japanese in central Japan (123 men, 111 women). Multiple linear regression models were used to assess role of dietary and other lifestyle traits in accounting for serum leptin difference between Hawaii and Japan. Mean leptin was significantly higher in Hawaii than Japan (7.2±6.8 vs 3.7±2.3 ng/ml in men, P<0.0001; 12.8±6.6 vs 8.5±5.0 in women <0.0001). In men, higher BMI in Hawaii explained over 90% of the difference in serum leptin; in women, only 47%. In multiple linear regression analyses in women, further adjustment for physical activity and dietary factors - - alcohol, dietary fiber, iron- - produced a further reduction in the coefficient for the difference, total reduction 70.7%; P value for the Hawaii-Japan difference became 0.126.

Conclusion

The significantly higher mean leptin concentration in Hawaii than Japan may be attributable largely to differences in BMI. Differences in nutrient intake in the two samples were associated with only modest relationship to the leptin difference.

Background and Aims

Heart failure (HF) remains a major public health issue. Red meat and dietary heme iron have been associated with an increased risk of coronary heart disease and hypertension, two major risk factors for HF. However, it is not known whether red meat intake influences the risk of HF. We therefore examined the association between red meat consumption and incident HF.

Methods and Results

We prospectively studied 21,120 apparently healthy men (mean age 54.6 y) from the Physicians’ Health Study (1982–2008). Red meat was assessed by an abbreviated food questionnaire and incident HF was ascertained through annual follow-up questionnaires. We used Cox proportional hazard models to estimate hazard ratios. In a multivariable model, there was a positive and graded relation between red meat consumption and HF [hazard ratio (95% CI) of 1.0 (reference), 1.02 (0.85–1.22), 1.08 (0.90–1.30), 1.17 (0.97–1.41), and 1.24 (1.03–1.48) from the lowest to the highest quintile of red meat, respectively (p for trend 0.007)]. This association was observed for HF with (p for trend 0. 035) and without (p for trend 0.038) antecedent myocardial infarction.

Conclusion

Our data suggest that higher intake of red meat is associated with an increased risk of HF.

Background and Aims

Metabolic syndrome (MetS) is a complex condition characterized by different phenotypes, according to combinations of risk factors and is associated with cardiovascular abnormalities. Whether control of MetS components by treatment produces improvement in the associated cardiovascular abnormalities is unknown. We investigated whether partial control of components of MetS was associated with less echocardiographic abnormalities than the complete presentation of MetS based on measured components.

Methods and Results

We evaluated markers of echocardiographic preclinical cardiovascular disease in MetS (ATPIII) defined by measured components or by history of treatment, in 1,421 African- American and 1,195 Caucasian non-diabetic HyperGEN participants, without prevalent cardiovascular disease or serum creatinine>2 mg/dL. Of 2,616 subjects, 512 subjects had MetS by measured components and 328 by history. Hypertension was found in 16% of participants without MetS, 6% of those with MetS by history and 42% of those with MetS by measured components. Obesity and central fat distribution had similar prevalence in both MetS groups (both p<0.0001 vs No-MetS). Blood pressure was similar in MetS by history and No-MetS, and lower than in MetS by measured components (p<0.0001). LV mass and midwall shortening, left atrial (LA) dimension and LA systolic force were similarly abnormal in both MetS groups (all p<0.0001 vs. No-MetS) without difference between them.

Conclusions

There is little impact of control by treatment of single components of MetS (namely hypertension) on echocardiographic abnormalities. Lower blood pressure in participants with MetS by history was not associated with substantially reduced alterations in cardiac geometry and function.

Background and Aims

The APOA1/C3/A4/A5 cluster encodes key regulators of plasma lipids. Interactions between dietary factors and single nucleotide polymorphisms (SNPs) in the cluster have been reported. Allostatic load, or physiological dysregulation in response to stress, has been implicated in shaping health disparities in ethnic groups. We aimed to determine the association between polymorphisms in the APOA1/C3/A4/A5 cluster with allostatic load parameters, alone, and in interaction with dietary fat intake in Puerto Ricans adults.

Methods and Results

Data on demographic and anthropometric measures, lifestyle behaviors, and medication use, as well as blood and urine samples for biomarker analysis, were obtained from participants of the Boston Puerto Rican Health Study (n=821, ages 45–75 y). The twelve polymorphisms analyzed were not associated with allostatic load parameters. Significant interactions were observed between dietary fat intake and APOA1 -75 in association with waist circumference (WC), (P=0.005), APOC3 -640 with diastolic blood pressure (DBP), (P=0.003), and APOA4 N147S and APOA5 S19W with systolic blood pressure (SBP), (P=0.001 and P=0.002, respectively). Puerto Ricans homozygous for the common allele of APOA1 -75, APOA4 N147S and APOA5 S19W had lower WC and SBP when consuming <31% of total fat from energy, than participants with the minor allele. Participants heterozygous for APOC3 -640 had lower DBP at total fat intake ≥ 31% from energy.

Conclusion

SNPs in APOA1/C3/A4/A5, as modulated by dietary fat intake, appear to influence allostatic load parameters in Puerto Ricans.

Background

Previous studies have shown that increased levels of C-reactive protein (CRP) predict cardiovascular events, including stroke, myocardial infarction and death from cardiovascular causes. Previous studies have also shown that increased levels of CRP are strong predictors of the progression of pre-existing carotid artery plaques. However, whether CRP is involved in the development of new plaques, that may or may not be associated with clinical events, in subjects with clean carotid arteries has been scarcely investigated

Methods

486 “InCHIANTI” Study participants (200 men and 286 women, 72% aged 65 years and over) free from carotid artery plaques at baseline, also underwent carotid artery scan three years later. We tested the association of baseline characteristics, cardiovascular risk factors and inflammatory markers with the development of new carotid artery plaques.

Results

Older participants were significantly more likely to develop new plaques. Independent of age, the relative risks of developing new plaques associated with heavy smoking and family history of atherosclerosis were 1.7 (95%CI 1.5-1.9) and 1.9 (95%CI 1.2-3.1), respectively. Participants with high (>3 microg/mL) and moderate (≥1 and ≤3 microg/mL) CRP levels had a relative risk of 2.2 (95%CI 1.9-2.6) and 1.9 (95%CI 1.6-2.3) respectively, when compared with subjects with low (<1 microg/mL) CRP levels. Surprisingly, risk factors such as hypertension, diabetes, dyslipidemia and overweight/obesity were not significantly predictors of the development of new carotid artery plaques.

Conclusions

High CRP levels independently predict the development of new plaques in older persons with carotid arteries free from atherosclerotic lesions.

Background

Modification of low density lipoprotein due to oxidative stress is essential in the development of coronary atherosclerosis. Data of specific carotenoids except β-carotene on cardioprotective effects in humans are limited.

Objective and methods

This study examined the associations between plasma concentrations of specific carotenoids and incidence of acute myocardial infarction. The study included 280 incident cases of acute myocardial infarction and 560 matched controls nested within the Singapore Chinese Health Study, a prospective cohort of 63,257 Chinese men and women aged 45 to 74 years old enrolled in 1993-1998 in Singapore. Retinol and carotenoids in prediagnostic plasma were quantified using high-performance liquid chromatography.

Results

High levels of plasma β-cryptoxanthin and lutein were associated with decreased risk of acute myocardial infarction after adjustment for multiple risk factors for coronary heart disease. For β-cryptoxanthin, the odds ratio (95% confidence interval) for the highest (Q5) versus the lowest (Q1) quintile was 0.67 (0.37-1.21) (P for trend = 0.03). For lutein, the odds ratios (95% confidence intervals) for Q2-Q3 and Q4-Q5 versus Q1 were 0.71 (0.45-1.12) and 0.58 (0.35-0.94) respectively (P for trend = 0.03). There was no statistically significant association between other carotenoids or retinol and risk of acute myocardial infarction.

Conclusions

High plasma levels of β-cryptoxanthin and lutein were associated with decreased risk of acute myocardial infarction. The findings of this study support a cardioprotective role of these two carotenoids in humans.

Background and Aims

Glycoprotein 6 (GP6) is a platelet-specific collagen receptor implicated in the thrombotic pathway to acute myocardial infarction (AMI), but a possible genetic relationship between GP6 and AMI is poorly understood. We tested for the genetic association between AMI and single nucleotide polymorphisms (SNPs) in 24 loci, including GP6.

Methods and Results

We conducted a case-control study of AMI and GP6 in a community-based population (n=652 cases, 625 controls). We also examined men and women separately and stratified the latter by use of hormone replacement therapy (HRT). Among both sexes, the strongest association was for a protective missense polymorphism (rs1163662) in the GP6 gene (OR=0.70; Bonferroni-adjusted p<0.05). SNPs in GP6 were also strongly associated with AMI among women who reported ever taking HRT, but not among women who never took HRT. Haplotype analyses were consistent with the single-SNP findings.

Conclusions

In this sample of white non-Hispanic men and women, several SNPs in GP6 were significantly related to risk of AMI. Development of pharmacologic therapy directed towards platelet activity and thrombosis may reduce the incidence of AMI among at-risk groups.

Background and Aims

The prevalence of insulin resistance and cardiovascular disease (CVD) increases with degree of obesity. Whether measurement of generalized or abdominal obesity differs in ability to predict changes associated with increased CVD risk is debated. We compared the prevalence of metabolic abnormalities in 275 women and 204 men stratified by categories of body mass index (BMI) and waist circumference (WC), and assessed the ability of these adiposity indices in combination with metabolic risk variables to predict insulin resistance.

Methods and Results

Healthy, non-diabetic volunteers underwent measurements of BMI, WC, blood pressure, fasting plasma glucose (FPG), lipoprotein concentrations, and direct quantification of insulin-mediated glucose uptake. Insulin resistance was defined as the top tertile of steady-state plasma glucose (SSPG) concentrations. BMI and WC were highly correlated (P <0.001) in both women and men. Abnormal SSPG and triglyceride concentrations were associated with increasing adiposity by either index in both genders. Among women, abnormal FPG and high density lipoprotein cholesterol (HDL-C) concentrations were associated with increasing BMI and WC. In men, abnormal HDL-C was associated with increasing BMI only. Elevated systolic blood pressure (SBP) was associated with increasing BMI in both genders. The odds of insulin resistance were greatest in women with elevated FPG and triglycerides (4.5-fold). In men, the best predictors were BMI and SBP, and WC and HDL-C (3-fold).

Conclusion

BMI is at least comparable to WC in stratifying individuals for prevalence of metabolic abnormalities associated with increased CVD risk and predicting insulin resistance.

Background and aims

There is little epidemiological evidence regarding the association of impaired glucose metabolism with recurrent cardiovascular events. We therefore examined potential sex differences in the effect of impaired fasting glucose (IFG) on recurrent cardiovascular disease (CVD) in a community-based study of survivors of a first acute myocardial infarction (MI).

Methods and results

This report focuses on 1,226 incident MI cases (28.4% women) discharged alive from area hospitals in the Western New York Acute MI Study (1996–2004). Deaths and underlying cause of death were determined via query of the National Death Index (Plus) Retrieval Program with follow-up through December 31, 2004. Outcomes reported included fatal or nonfatal coronary heart disease (CHD) or coronary revascularization surgery and total stroke. Traditional CHD risk factors and other explanatory variables were determined by clinical examination after the first acute event. Impaired fasting glucose was defined as fasting blood glucose between 100 and 125 mg/dl. During a mean follow-up of 4.5 years, there were 91 recurrent events (26.1%) in women and 173 recurrent events (19.7%) in men. After multivariable adjustment, the hazard ratios for recurrent cardiovascular events were 1.96 (95% CI: 1.15–3.16) and 2.59 (1.56–4.30) in women with IFG and with diabetes, respectively, compared to normoglycemic women. Among men, neither IFG nor diabetes was independently related to risk of recurrence.

Conclusions

In this study, IFG was a strong risk factor for recurrent cardiovascular events only among women. These results suggest that increased cardiovascular risk in MI survivors begins at lower glucose levels in women than men.

Background and Aims

Homocysteine (Hcy) is a sulfur-containing, non-protein amino acid produced in the metabolic pathway of methionine. Hyperhomocysteinemia is associated with cerebro- and cardiovascular disease in industrialized countries mostly resulting from protein rich diet and sedentary life style. Matrix metalloproteinases are involved in cardiac remodeling, leading to degradation of intercellular junctions, cardiac connexins and basement membranes. The study was designed to investigate the relationship between Hcy, cardiac remodeling, cardiac performance, and rhythm disturbances in an animal model of hyperhomocysteinemia. We tested the hypothesis that induction of matrix metalloproteinase-2 and matrix metalloproteinase-9 leads to connexin 40, connexin 43, connexin 45 expression changes contributing to decreased cardiac performance and disturbed atrioventricular conduction.

Methods and Results

Hcy was added to drinking water of male C57/BL6J mice to achieve moderate Hcy blood levels. ECG was monitored in conscious mice with a telemetric ECG device; echocardiography was used for assessment of left ventricular function. Immunoblotting was used to evaluate matrix metalloproteinase-2, matrix metalloproteinase-9, connexin 40, connexin 43, and connexin 45 expression in cardiac tissue. Animals fed Hcy showed significant prolongation of QRS, QTc, and PR intervals along with reduced left ventricular function. Western blotting showed increased expression of matrix metalloproteinase-2, matrix metalloproteinase-9 and decreased expression of connexin 40, 43, and 45.

Conclusion

Hcy has been identified as a nutritional factor contributing to cardiovascular disease. Cardiac remodelling induced by matrix metalloproteinase-2 and matrix metalloproteinase-9 and decreased expression of connexin 40, 43, and 45 appears to play a role in the pathomechansim of atrioventricular conduction delay and ventricular dilatation in hyperhomocysteinemia.

Background and aims

It was reported that high coffee consumption was related to decreased diabetes risk. The aim of this study is to examine the association between coffee consumption and the incidence of type 2 diabetes in persons with normal glucose tolerance in a population with a high incidence and prevalence of diabetes.

Methods and results

In a prospective cohort study, information about daily coffee consumption was collected at the baseline examination (1989-1992) in a population-based sample of American Indian men and women 45-74 years of age. Participants with normal glucose tolerance (N=1141) at the baseline examination were followed for an average of 7.6 years. The incidence of diabetes was compared across the categories of daily coffee consumption. The hazard ratios of diabetes related to coffee consumption were calculated using Cox proportional hazards models, adjusted for potential confounders.

Levels of coffee consumption were positively related to levels of current smoking and inversely related to body mass index, waist circumference, female gender, and hypertension. Compared to those who did not drink coffee, participants who drank 12 or more cups of coffee daily had 67% less risk of developing diabetes during the follow-up (hazard ratio: 0.33, 95% confidence interval: 0.13, 0.81).

Conclusion

In this population, a high level of coffee consumption was associated with a reduced risk of deterioration of glucose metabolism over an average 7.6 years of follow-up. More work is needed to understand whether there is a plausible biological mechanism for this observation.

BACKGROUND AND AIMS

Although dietary fats and cholesterol have previously been associated with risk of cardiovascular disease (CVD) in middle aged populations, less is known among older adults. The purpose of this study was to determine the association between dietary fats, cholesterol, and eggs and CVD risk among community-dwelling adults aged 70–79 in the Health, Aging and Body Composition Study.

METHODS AND RESULTS

Diet was assessed using an interviewer-administered 108-item food frequency questionnaire (n=1,941). CVD events were defined as a confirmed myocardial infarction, coronary death, or stroke. Relative rates of CVD over 9 years of follow-up were estimated using Cox proportional hazards models. During follow-up, there were 203 incident cases of CVD. There were no significant associations between dietary fats and CVD risk. Dietary cholesterol (HR (95% CI): 1.47 (0.93, 2.32) for the upper vs. lower tertile; P for trend, 0.10) and egg consumption (HR (95% CI): 1.68 (1.12, 2.51) for 3+/week vs. <1/week); P for trend, 0.01) were associated with increased CVD risk. However, in subgroup analyses, dietary cholesterol and egg consumption were associated with increased CVD risk only among older adults with type 2 diabetes (HR (95% CI): 3.66 (1.09, 12.29) and 5.02 (1.63, 15.52), respectively, for the upper vs. lower tertile/group).

CONCLUSIONS

Dietary cholesterol and egg consumption were associated with increased CVD risk among older, community-dwelling adults with type 2 diabetes. Further research on the biological mechanism(s) for the increased CVD risk with higher dietary cholesterol and frequent egg consumption among older adults with diabetes is warranted.

Background and Aims

Arterial stiffness is a prominent feature of vascular aging and a risk factor for cardiovascular disease (CVD). Fat around the heart and blood vessels (i.e. pericardial fat, Pfat) may contribute to arterial stiffness via a local paracrine effect of adipose tissue on the surrounding vasculature. Thus, we determined the association between Pfat and carotid stiffness in 5,770 participants (mean age 62 yrs, 53% female, 25% African American, 24% Hispanic, and 13% Chinese) from the Multi-Ethnic Study of Atherosclerosis.

Methods and Results

Pfat was measured by computed tomography, and ultrasonography of the common carotid artery was used to calculate the distensibility coefficient (DC) and young’s modulus (YM). Lower DC and higher YM values indicate stiffer arteries. Pfat quartile was highly associated with demographic, behavioral, anthropometric, hemodynamic, metabolic, and disease variables in both men and women. After adjusting for height, clinical site, CVD risk factors, and medications, a 1-standard deviation (41.91 cm3) increment in Pfat was associated with a 0.00007±0.00002 1/mmHg lower DC (p=0.0002) in men and a 48.1±15.1 mmHg/mm higher YM in women (p=0.002). Additional adjustment for C-reactive protein, coronary artery calcification, and carotid intima-media thickness had only modest effects. More importantly, adjusting for body mass index and waist circumference did not significantly change the overall results.

Conclusion

Higher Pfat is associated with higher carotid stiffness, independent of traditional CVD risk factors and obesity.

Macronutrient intakes and genetic variants have been shown to interact to alter the risk of insulin resistance, but replication of gene-nutrient interactions across independent populations may be difficult to achieve. Saturated fat and carbohydrate were previously shown to interact with genotype for insulin resistance for a variant of perilipin (PLIN), the major adipocyte-associated protein and a regulator of adipocyte metabolism. We investigated the same interaction for PLIN 11482G>A (rs894160) on insulin resistance in US men(n=462) and women(n=508) (mean ±SD, 49±16 years). In multivariate linear regression models, we found a significant (P<0.05) interaction between the ratio of saturated fat to carbohydrate intake as a continuous variable and PLIN 11482G>A for HOMA-IR (homeostasis model assessment of insulin resistance) in women. For carriers of the minor allele but not for non-carriers, as the ratio of saturated fat to carbohydrate intake increased, predicted HOMA-IR increased significantly (P=0.002). By dichotomizing the ratio of saturated fat to carbohydrate intake into high and low, we found significant interaction terms for insulin and HOMA-IR (P<0.05). When the ratio of saturated fat to carbohydrate was high, insulin and HOMA-IR were higher in minor allele carriers (P=0.004 and P=0.003, respectively), but did not differ when the ratio was low. Similar patterns or trends were observed when saturated fat and carbohydrate were dichotomized into high and low as individual macronutrients. Replication of the previously reported interaction between macronutrient intakes and PLIN genotype for insulin resistance reinforces the potential usefulness of applying genotype information in the dietary management of insulin resistance.

Background and Aims

Studies evaluating the effect of legume consumption on cholesterol have focused on soybeans, however non-soy legumes, such as a variety of beans, peas, and some seeds, are commonly consumed in Western countries. We conducted a meta-analysis of randomized controlled trials evaluating the effects of non-soy legume consumption on blood lipids.

Methods and Results

Studies were retrieved by searching MEDLINE (from January 1966 through July 2009), EMBASE (from January 1980 to July 2009), and the Cochrane Collaboration's Central Register of Controlled Clinical Trials using the following terms as medical subject headings and keywords: fabaceae not soybeans not isoflavones and diet or dietary fiber and cholesterol or hypercholesterolemia or triglycerides or cardiovascular diseases. Bibliographies of all retrieved articles were also searched. From 140 relevant reports, 10 randomized clinical trials were selected which compared a non-soy legume diet to control, had a minimum duration of 3 weeks, and reported blood lipid changes during intervention and control. Data on sample size, participant characteristics, study design, intervention methods, duration, and treatment results were independently abstracted by 2 investigators using a standardized protocol. Data from 10 trials representing 268 participants were examined using a random-effects model. Pooled mean net change in total cholesterol for those treated with a legume diet compared to control was −11.8 mg/dL (95% confidence interval [CI], −16.1 to −7.5); mean net change in low density lipoprotein cholesterol was −8.0 mg/dL (95% CI, −11.4 to −4.6).

Conclusion

These results indicate that a diet rich in legumes other than soy decreases total and LDL cholesterol.

Background and Aims

Vitamin D deficiency has been associated with the etiology and pathogenesis of heart disease including congestive heart failure. We previously observed cardiac hypertrophy in vitamin D deficient rats and vitamin D-receptor knockout mice. These studies indicate that the absence of vitamin D-mediated signal transduction and genomic activation results in increased sensitivity of the heart to ionotropic stimuli and cardiomyocyte hypertrophy. This study’s aim is to investigate the relationship between vitamin D status and the heart failure phenotype in the rat.

Methods and Results

Vitamin D status was assessed by measuring 25-hydroxyvitamin D levels and related to heart weight in young, middle-aged and aging spontaneously hypertensive, heart failure-prone (SHHF) rats. We also measured the effects of the vitamin D hormone,1,25(OH)2D3, on cardiac function in SHHF rats. Cardiac hypertrophy in this model of the failing heart increased with age and related to decreasing vitamin D status. Vitamin D deficiency presented after cardiac hypertrophy was first observed. Additionally, we found that 1,25(OH)2D3 treatment between 4.0–7.0 months of age prevented cardiac hypertrophy and permits decreased workload for the heart while allowing adequate blood perfusion and pressure, resulting in reduced cardiac index.

Conclusions

Our findings suggest that low vitamin D status is associated with the progression and final terminal phase of the heart failure phenotype and not with initial heart hypertrophy. Also, we report that in the vitamin D sufficient SHHF rat, 1,25(OH)2D3 treatment provided protection against the progression of the heart failure phenotype.

Background and aims

Atherosclerosis is known to be an inflammatory disease and there is increasing evidence that chylomicron remnants (CMR), the lipoproteins which carry dietary fats in the blood, cause macrophage foam cell formation and inflammation. In early atherosclerosis the frequency of activated monocytes in the peripheral circulation is increased, and clearance of CMR from blood may be delayed, however, whether CMR contribute directly to monocyte activation and subsequent egress into the arterial wall has not been established. Here, the contribution of CMR to activation of monocyte pro-inflammatory pathways was assessed using an in vitro model.

Methods and results

Primary human monocytes and CMR-like particles (CRLP) were used to measure several endpoints of monocyte activation. Treatment with CRLP caused rapid and prolonged generation of reactive oxygen species by monocytes. The pro-inflammatory chemokines MCP-1 and IL-8 were secreted in nanogram quantities by the cells in the absence of CRLP. IL-8 secretion was transiently increased after CRLP treatment, and CRLP maintained secretion in the presence of pharmacological inhibitors of IL-8 production. In contrast, exposure to CRLP significantly reduced MCP-1 secretion. Chemotaxis towards MCP-1 was increased in monocytes pre-exposed to CRLP and was reversed by addition of exogenous MCP-1.

Conclusion

Our findings indicate that CRLP activate human monocytes and augment their migration in vitro by reducing cellular MCP-1 expression. Our data support the current hypothesis that CMR contribute to the inflammatory milieu of the arterial wall in early atherosclerosis, and suggest that this may reflect direct interaction with circulating blood monocytes.

Background and aims

To examine whether the association between the -514C/T polymorphism of the hepatic lipase gene and myocardial infarction (MI) is modified by history of hypercholesterolemia and increased waist circumference.

Methods and results

1940 pairs of nonfatal MI cases and population-based controls were genotyped. Multiple conditional logistic regression was used for data analyses. The -514T variant was not associated with MI in the whole population. However, among people with history of hypercholesterolemia the T allele increased MI risk for heterozygous and homozygous carriers, respectively [OR=1.25 (95%CI=0.92-1.70) and OR=1.59 (95%CI=1.09-2.32). In contrast, the T allele decreased MI risk among people with no history of hypercholesterolemia [OR=0.85 (95%CI=0.70-1.03) and OR=0.76 (95%CI=0.60-0.97)], p for interaction=0.004. Among subjects with normal waist circumference there was no association between the -514T allele and MI for heterozygous and homozygous carriers, respectively [OR=1.04 (95%CI=0.86-1.25) and OR=0.96 (95%CI=0.77-1.21)], while among subjects with waist circumference above the limits of the metabolic syndrome definition there was a protective association [OR=0.63 (95%CI=0.45-0.90) and OR=0.81 (95%CI=0.53-1.25) p for interaction=0.04].

Conclusion

The -514 T allele is associated with MI in opposite directions depending on the background of the studied population. This could explain what seem like inconsistent results across studies.

Background and aims

IL-18 expression is up-regulated in atherosclerotic plaques, and higher levels are seen in obese and Type 2 Diabetic individuals. More recently, a possible role for IL-18 in glucose and energy homeostasis has been suggested.

Methods and results

We investigated variation within the IL18 gene and its association with measures of obesity and the metabolic syndrome. Five IL18 tagging single nucleotide polymorphisms (rs1946519, rs2043055, rs549908, rs360729, rs3882891) were selected and genotyped in the Gene-Diet Attica Investigation on childhood obesity (GENDAI) (age range 10–14 yrs); in young European men in the second European Atherosclerosis Research offspring Study (EARSII), an offspring study (age range 18–28 yrs) and in a group of healthy women from the Greek Obese Women study (GrOW) (age range 18–74 yrs). Six common haplotypes were observed. In GrOW, Hap6 (Frequency-2.6%) was associated with higher insulin levels (p < 0.0001), estimates of HOMA-Insulin Resistance (p < 0.0001) and HOMA-β-cell (p < 0.0001) compared to the common haplotype Hap1 (Frequency-33.2%). In EARSII, rs2043055 was associated with peak and area under the curve triglycerides (p = 0.001 and p = 0.002, respectively) after an oral fat tolerance test in ‘cases’ but not ‘controls’. None of the haplotypes were associated with measures of body fatness in any of the studies.

Conclusion

Association of IL18 variation with insulin levels and estimates of insulin resistance were only observed in our adult study, suggesting that the effects of IL-18 are only associated with increasing age. Taken together with the association of IL18 variants with post-prandial measures, this provides support for IL-18 as a metabolic factor.

Background and Aims

Although Eskimos were thought to be protected from cardiovascular disease (CVD), state health data show a large proportion of deaths from CVD, despite traditional lifestyles and high omega-3 fatty acid intake. This article explores CVD prevalence and its relation to risk factors in Alaska Eskimos.

Methods and Results

A population-based cohort of 499 Alaska Eskimos > age 45 from the Norton Sound region was examined in 2000-2004 for CVD and associated risk factors as part of the Genetics of Coronary Artery Disease in Alaska Natives study. CVD and atherosclerosis were evaluated and adjudicated using standardized methods. Average age was 58y; diabetes prevalence was low and high-density lipoprotein cholesterol (HDL-C) concentrations were high, but a large proportion smoked and had high pathogen burden. CVD was higher in men (12.6%) than in women (5.3%) (prevalence ratio 2.4, CI 1.3-4.4). Rates of stroke (6.1% in men, 1.8% in women) were similar to those for coronary heart disease (CHD) (6.1% men, 2.5% women). MI prevalence was low in both genders (1.9% and 0.7%). CVD was higher in men and in those >60 yrs. Hypertension, diabetes, high LDL-C, high apoB, and low HDL-C were all strong correlates (<.002) and albuminuria and CRP were also correlated with CVD (p<.05) after adjustment for age and gender. Carotid atherosclerosis was correlated with CVD (p=.0079) independent of other risk factors.

Conclusion

These data show high CHD and stroke prevalence in Alaska Eskimos, despite low average LDL-C and high HDL-C. Hypertension and high LDL-C were independent correlates; identifying these risk factors early and treating to target is recommended.

Background and aims

Several genes have been shown to individually affect plasma lipoprotein metabolism in humans. Studies on gene-gene interactions could offer more insight into how genes affect lipid metabolism and may be useful in predicting lipid concentrations. We tested for gene-gene interactions between TaqIB SNP in the cholesterol ester transfer protein (CETP) and three novel single nucleotide polymorphisms (SNPs), namely rs11774572, rs7819412 and rs6995374 for their effect on metabolic syndrome (MetS) components and related traits.

Methods and results

The aforementioned SNPs were genotyped in 1002 subjects who participated in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study. Lipids were measured by standard procedures and lipoprotein subfractions, by proton nuclear magnetic resonance spectroscopy. Polymorphism rs11774572 was significantly associated with MetS (P=0.020), mainly driven by the association of the C allele with lower HDL-C (P=0.043) and higher triglycerides (P=0.049) and insulin (P=0.040) concentrations than TT subjects. A significant interaction between SNPs rs11774572 and CETP-TaqIB SNPs was found for HDL-C concentrations (P=0.006) and for HDL (P=0.008) and LDL particle sizes (P=0.009), small LDL (P=0.004), and VLDL concentrations (P=0.021), in which TT homozygotes displayed higher HDL-C concentrations and for HDL and LDL particle sizes, and lower small LDL and VLDL concentrations than C carriers, if they were CETP B2 allele carriers (P values ranging from <0.001 to 0.001).

Conclusions

The rs11774572 polymorphism may play a role in the dyslipidemia that characterizes MetS. The interaction between rs11774572 and CETP-TaqIB SNPs on HDL-C concentrations provides some insights into the underlying mechanisms.

Background and aims

The increase in breast cancer incidence over recent decades has been accompanied by an increase in the frequency of metabolic syndrome. Several studies suggest that breast cancer risk is associated with the components of metabolic syndrome (high serum glucose and triglycerides, low HDL-cholesterol, high blood pressure, and abdominal obesity), but no prospective study has investigated risk in relation to the presence of explicitly defined metabolic syndrome. We investigated associations between metabolic syndrome, its components, and breast cancer risk in a nested case-control study on postmenopausal women of the ORDET cohort.

Methods and results

After a median follow-up of 13.5 years, 163 women developed breast cancer; metabolic syndrome was present in 29.8%. Four matched controls per case were selected by incidence density sampling, and rate ratios were estimated by conditional logistic regression. Metabolic syndrome (i.e. presence of three or more metabolic syndrome components) was significantly associated with breast cancer risk (rate ratio 1.58 [95% confidence interval 1.07–2.33]), with a significant risk increase for increasing number of components (P for trend 0.004). Among individual metabolic syndrome components, only low serum HDL-cholesterol and high triglycerides were significantly associated with increased risk.

Conclusions

This prospective study indicates that metabolic syndrome is an important risk factor for breast cancer in postmenopausal women. Although serum HDL-cholesterol and triglycerides had the strongest association with breast cancer, all components may contribute to increased risk by multiple interacting mechanisms. Prevention or reversal of metabolic syndrome by life-style changes may be effective in preventing breast cancer in postmenopausal women.