Stefania Lamon-fava | Tufts University (original) (raw)

Papers by Stefania Lamon-fava

Research paper thumbnail of Comparing fluorescence-based cell-free assays for the assessment of antioxidative capacity of high-density lipoproteins

Lipids in health and disease, Jan 22, 2016

Population studies have shown an inverse association between high-density lipoprotein (HDL) chole... more Population studies have shown an inverse association between high-density lipoprotein (HDL) cholesterol levels and risk of coronary heart disease (CHD). HDL has different functions, including the ability to protect biological molecules from oxidation. Our aim was to evaluate the performance of two fluorescence-based assays in assessing the antioxidative capacity of HDL. We compared the antioxidative capacity of HDL with the phospholipid 2',7'-dichlorodihydrofluorescein (DCF) assay and the dihydrorhodamine 123 (DHR) assay in controls and in subjects at increased risk of CHD, including subjects with established CHD, and subjects with elevated plasma triglycerides (TG), serum amyloid A (SAA), or myeloperoxidase (MPO) levels. The antioxidative capacity of HDL, as measured by the DCF assay, was significantly lower in both CHD and high-TG patients than in controls (p < 0.001 and p = 0.004, respectively). Interestingly, the mean antioxidative capacity of HDL in high-SAA subjects...

Research paper thumbnail of Effects of oral eicosapentaenoic acid versus docosahexaenoic acid on human peripheral blood mononuclear cell gene expression

Atherosclerosis, Jan 19, 2015

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have beneficial effects on inflammatio... more Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have beneficial effects on inflammation and cardiovascular disease (CVD). Our aim was to assess the effect of a six-week supplementation with either olive oil, EPA, or DHA on gene expression in peripheral blood mononuclear cells (PBMC). Subjects were sampled at baseline and six weeks after receiving either: olive oil 6.0 g/day (n = 16), EPA 1.8 g/day (n = 16), or DHA 1.8 g/day (n = 18). PBMC were subjected to gene expression analysis by microarray with key findings confirmed by quantitative real-time polymerase chain reaction (Q-PCR). Plasma phospholipid EPA increased 3 fold in the EPA group, and DHA increased 63% in the DHA group (both p < 0.01), while no effects were observed in the olive oil group. Microarray analysis indicated that EPA but not DHA or olive oil significantly affected the gene expression in the following pathways: 1) interferon signaling, 2) receptor recognition of bacteria and viruses, 3) G protein sig...

Research paper thumbnail of Gene-Environment Interactions of Circadian-Related Genes for Cardiometabolic Traits

Diabetes care, Jan 17, 2015

Common circadian-related gene variants associate with increased risk for metabolic alterations in... more Common circadian-related gene variants associate with increased risk for metabolic alterations including type 2 diabetes. However, little is known about whether diet and sleep could modify associations between circadian-related variants (CLOCK-rs1801260, CRY2-rs11605924, MTNR1B-rs1387153, MTNR1B-rs10830963, NR1D1-rs2314339) and cardiometabolic traits (fasting glucose [FG], HOMA-insulin resistance, BMI, waist circumference, and HDL-cholesterol) to facilitate personalized recommendations. We conducted inverse-variance weighted, fixed-effect meta-analyses of results of adjusted associations and interactions between dietary intake/sleep duration and selected variants on cardiometabolic traits from 15 cohort studies including up to 28,190 participants of European descent from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We observed significant associations between relative macronutrient intakes and glycemic traits and short sleep duration (<7 h...

Research paper thumbnail of Clock Genes Explain a Large Proportion of Phenotypic Variance in Systolic Blood Pressure and This Control Is Not Modified by Environmental Temperature

American journal of hypertension, Jan 4, 2015

Diurnal variation in blood pressure (BP) is regulated, in part, by an endogenous circadian clock;... more Diurnal variation in blood pressure (BP) is regulated, in part, by an endogenous circadian clock; however, few human studies have identified associations between clock genes and BP. Accounting for environmental temperature may be necessary to correct for seasonal bias. We examined whether environmental temperature on the day of participants' assessment was associated with BP, using adjusted linear regression models in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) (n = 819) and the Boston Puerto Rican Health Study (BPRHS) (n = 1,248) cohorts. We estimated phenotypic variance in BP by 18 clock genes and examined individual single-nucleotide polymorphism (SNP) associations with BP using an additive genetic model, with further consideration of environmental temperature. In GOLDN, each additional 1 °C increase in environmental temperature was associated with 0.18mm Hg lower systolic BP [SBP; β ± SE = -0.18±0.05mm Hg; P = 0.0001] and 0.10mm Hg lower diastolic BP [DBP; ...

Research paper thumbnail of Docosahexaenoic acid differentially affects TNFα and IL-6 expression in LPS-stimulated RAW 264.7 murine macrophages

Prostaglandins, Leukotrienes and Essential Fatty Acids (PLEFA), 2015

Docosahexaenoic acid (DHA) is generally reported to have anti-inflammatory properties, however, p... more Docosahexaenoic acid (DHA) is generally reported to have anti-inflammatory properties, however, prior work has documented differential effects on individual pro-inflammatory cytokines: reduced IL-6, but not TNFα, mRNA expression in macrophages. To elucidate the mechanism, the roles of prostaglandin E 2 (PGE 2 ), cyclic AMP response element-binding protein (CREB), and NFκB were examined in RAW 264.7 macrophages. DHA did not influence CREB activity, but significantly reduced PGE 2 production by 41% and NFκB activity by 32%. Exogenous PGE 2 inhibited TNFα mRNA expression dose dependently. Unexpectedly, inhibiting PGE 2 production with NS-398 also decreased TNFα mRNA expression, suggesting a concentration-dependent dual role of PGE 2 in regulating TNFα expression. IL-6 expression was unaffected by endogenous or exogenous PGE 2 . Partial block of NFκB activation (SN50; 46%, or, BAY-11-7082; 41%) lowered IL-6 to a greater extent than TNFα mRNA expression. The differential effect of DHA on TNFα and IL-6 mRNA expression may be mediated via reduction in NFκB activity.

Research paper thumbnail of Association between statin use and serum cholesterol concentrations is modified by whole-grain consumption: NHANES 2003-2006

The American journal of clinical nutrition, 2014

Statins are used to lower cardiovascular disease risk in part because of their effects on plasma ... more Statins are used to lower cardiovascular disease risk in part because of their effects on plasma lipid profiles. Dietary whole grains have been reported to improve plasma lipid profiles. Little is known about potential interactions between statins and whole grains. We aimed to assess the interaction between statin use and whole-grain intake in relation to serum lipid concentrations in adults. In this cross-sectional study, we used data from 4284 adults aged ≥45 y with reliable and complete dietary data who were participating in the NHANES 2003-2006. Usual whole-grain intake was estimated from two 24-h diet recalls by using the MyPyramid Equivalents Database. Participants self-reported statin use. Total cholesterol and HDL-cholesterol concentrations were measured in all adult participants. The non-HDL-cholesterol concentration and total cholesterol:HDL-cholesterol ratio were calculated. Multiple linear and logistic regression models were used for analyses. Statin usage was 24.9% in a...

Research paper thumbnail of Serotonin transporter polymorphisms and adverse effects with fluoxetine treatment

The short (S) allele of the serotonin transporter gene-linked polymorphic region (5HTTLPR) has be... more The short (S) allele of the serotonin transporter gene-linked polymorphic region (5HTTLPR) has been associated with poorer antidepressant response in major depressive disorder (MDD) and with antidepressant-induced mania. This study investigated a possible association with treatment-emergent insomnia or agitation. Methods: Thirty-six outpatients with MDD were genotyped at 5HTTLPR and treated with open-label fluoxetine up to 60 mg/day. Treatment-emergent adverse effects were assessed at each study visit. Results: Of nine subjects homozygous for the "S" allele, seven (78%) developed new or worsening insomnia, versus 6 of 27 (22%) non-"S"-homozygous subjects (Fisher's exact p ϭ .005). Similarly, six of nine subjects homozygous for the "S" allele (67%) developed agitation, versus 2 of 27 (7%) of non-"S"-homozygous subjects (Fisher's exact p ϭ .001). Conclusions: The "S" allele of the 5HTTLPR may identify patients at risk for developing insomnia or agitation with fluoxetine treatment. This preliminary result requires confirmation in larger samples.

Research paper thumbnail of Dietary modulators of statin efficacy in cardiovascular disease and cognition

Molecular Aspects of Medicine, 2014

Research paper thumbnail of Buspirone Therapy for Type A Behavior, Hostility, and Perceived Stress in Cardiac Patients

Psychotherapy and Psychosomatics, 1993

Hostility is considered to be a risk factor for coronary artery disease. Despite the findings of ... more Hostility is considered to be a risk factor for coronary artery disease. Despite the findings of reduced serotonergic function and effectiveness of treatment with serotonergic agents in similar symptom complexes, there have been no attempts at using serotonergic psychopharmacologic agents to treat this population. We conducted an 8-week open trial of 10 type A, irritable men with coronary artery disease and no diagnosable psychiatric (axis I) condition to examine the effects of buspirone on these subjects. Buspirone appears to significantly reduce type A behavior, hostility, anxiety, impatience, and perceived stress.

Research paper thumbnail of Effects of estrogen replacement on plasma lipoproteins and apolipoproteins in postmenopausal, dyslipidemic women

Metabolism, 1992

The effects of oral estrogen replacement (ethinyl estradiol 0.02 mg/d) on plasma triglyceride, to... more The effects of oral estrogen replacement (ethinyl estradiol 0.02 mg/d) on plasma triglyceride, total cholesterol, very-lowdensity lipoprotein (VLDL) cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and apolipoprotein (apo) A-l and B levels and LDL particle size were assessed in 20 postmenopausal women with a previous hysterectomy and various forms of dyslipidemia (LDL cholesterol L 4.14 mmol/L [160 mg/dL] and/or HDL cholesterol s 1.03 mmol/L (40 mg/dL]). All subjects were studied while on a standard cholesterol-lowering diet, and were sampled in the fasting state before beginning estrogen therapy and after a mean of 13 weeks of estrogen therapy. Lipids were measured by standardized enzymatic techniques, apos were measured by enzyme-linked immunoassays, and LDL particle size was measured by gradient gel electrophoresis. Mean values for plasma lipid parameters (mmol/L) at baseline and during estrogen replacement were as follows: triglyceride, 2.11 and 2.75 (30% increase); total cholesterol, 7.45 and 6.52 (13% decrease); VLDL cholesterol, 1.09 and 1.22 (12% increase); LDL cholesterol, 5.09 and 3.70 (27% decrease); and HDL cholesterol, 1.27 and 1.56 (24% increase). Mean values for apo A-l were 163 and 254 mg/dL (56% increase), and for apo B they were 170 and 148 mg/dL (13% decrease). The LDL particle score was 4.09 and 4.52 (11% smaller). Changes in all parameters were statistically significant (P = .05) except for VLDL cholesterol. These data indicate that estrogen replacement is effective in decreasing LDL cholesterol and apo B concentrations and increasing HDL cholesterol and apo A-l concentrations in dyslipidemic postmenopausal women, but it should not be used in patients with baseline fasting triglyceride levels higher than 2.82 mmol/ L (250 mg/dL) unless it is accompanied by a progestin. Our data indicate that this form of estrogen replacement could lower the risk of coronary artery disease (CAD) by more than 50% in these women, based on favorable alterations in plasma lipoproteins.

Research paper thumbnail of Physiologic benefits of a stress reduction program for healthy middle-aged army officers

Journal of Psychosomatic Research, 1993

Stress reduction programs (SRPs) can reduce morbidity and mortality in patients with coronary art... more Stress reduction programs (SRPs) can reduce morbidity and mortality in patients with coronary artery disease (CAD). This study evaluated the effect of an SRP on metabolic and hormonal risk factors for CAD. Twenty army officers participating in an SRP, Group I, and a comparison group of seventeen SRP nonparticipants, Group C, volunteered to undergo measurement of dehydroepiandrosterone-sulfate (DHEA-S), cortisol, DHEA-S/cortisol ratio, testosterone, apolipoprotein-A1, apolipoprotein-B, triglycerides, cholesterol, fibrinogen, and leukocyte count both before and after the SRP period. No differences in the changes in biochemical risk factors for CAD were found between participant and nonparticipant except for DHEA-S. While Group C had a marked reduction in DHEA-S levels, Group I had a small increase. Previous studies indicate DHEA-S is inversely associated with extent of CAD and age-adjusted DHEA-S levels below 3.78 mumol/l confer an increased risk for CAD mortality. SRP participation appears to effect DHEA-S levels, possibly partially accounting for the benefits observed in SRPs among CAD patients.

Research paper thumbnail of Association of polymorphisms in genes involved in lipoprotein metabolism with plasma concentrations of remnant lipoproteins and HDL subpopulations before and after hormone therapy in postmenopausal women

Clinical Endocrinology, 2010

Objective-A high degree of inter-individual variability in plasma lipid level response to hormone... more Objective-A high degree of inter-individual variability in plasma lipid level response to hormone therapy (HT) has been reported. Variations in the oestrogen receptor α gene (ESR1) and in genes involved in lipid metabolism may explain some of the variability in response to HT.

Research paper thumbnail of Adiponectin: An independent risk factor for coronary heart disease in men in the Framingham offspring Study

Atherosclerosis, 2011

Objective: Our aim was to determine whether plasma adiponectin levels were an independent predict... more Objective: Our aim was to determine whether plasma adiponectin levels were an independent predictor of coronary heart disease (CHD) risk. Methods and results: Plasma adiponectin levels were measured in 3188 male and female participants from cycle 6 of the Framingham offspring Study (mean age: 57 years in both men and women; BMI: 28.5 kg/m 2 in men and 27.3 kg/m 2 in women), using a novel fully automated assay. Plasma adiponectin levels (median [25th percentile, 75th percentile]) were significantly higher in female than in male CHDfree subjects (14.8 [10.7,20.5] g/ml versus 9.0 [7.0,12.2] g/ml, p < 0.001). Participants were followed for a mean of 7.5 years. After adjustment for age, BMI, smoking status, systolic blood pressure, treatment for hypertension, diabetes, use of cholesterol-lowering medication, total cholesterol level, high-density lipoprotein cholesterol level, and C-reactive protein levels, a higher plasma adiponectin level was a significant predictor of lower risk of future CHD events (n = 117) in men (HR 0.49, p < 0.0022). A similar trend was observed in women, but was no longer significant after multivariate adjustments. Conclusions: Our data indicate that plasma adiponectin levels are an independent predictor of CHD in Caucasian men initially free of CHD.

Research paper thumbnail of Apolipoprotein B metabolism in humans: studies with stable isotope-labeled amino acid precursors

Atherosclerosis, 2002

This article reviews the literature from 1986 to early 2001 relating to apoB100 and apoB48 kineti... more This article reviews the literature from 1986 to early 2001 relating to apoB100 and apoB48 kinetics in humans using amino acid precursors labeled with stable isotopes. The following subjects are reviewed: (1) methodology; (2) normal individuals and the effects of aging; (3) diet; (4) hereditary dyslipidemias: familial hypercholesterolemia, familial combined hyperlipidemia, cholesteryl ester storage disease, cholesteryl ester transfer protein deficiency, lipoprotein lipase deficiency, familial hypobetalipoproteinemia, and truncated forms of apoB; (5) hormonal perturbations: estrogen, insulin, diabetes, obesity, and growth hormone; (6) the nephrotic syndrome; and (7) the effects of the statin class of drugs. Because of the advances which have been made in mass spectrometry techniques, the advantages of using non-radioactive tracers in humans have made stable isotope kinetic studies the present day standard in this area of research.

Research paper thumbnail of Plasma Phosphatidylcholine Docosahexaenoic Acid Content and Risk of Dementia and Alzheimer Disease

Archives of Neurology, 2006

Docosahexaenoic acid (DHA) is an abundant fatty acid in the brain. In the diet, DHA is found most... more Docosahexaenoic acid (DHA) is an abundant fatty acid in the brain. In the diet, DHA is found mostly in fatty fish. The content of DHA has been shown to be decreased in the brain and plasma of patients with dementia. To determine whether plasma phosphatidylcholine (PC) DHA content is associated with the risk of developing dementia. A prospective follow-up study in 899 men and women who were free of dementia at baseline, had a median age of 76.0 years, and were followed up for a mean of 9.1 years for the development of all-cause dementia and Alzheimer disease. Plasma PC fatty acid levels were measured at baseline. Cox proportional regression analysis was used to assess relative risks of all-cause dementia and Alzheimer disease according to baseline plasma levels. Ninety-nine new cases of dementia (including 71 of Alzheimer disease) occurred during the follow-up. After adjustment for age, sex, apolipoprotein E epsilon4 allele, plasma homocysteine concentration, and education level, subjects in the upper quartile of baseline plasma PC DHA levels, compared with subjects in the lower 3 quartiles, had a relative risk of 0.53 of developing all-cause dementia (95% confidence interval, 0.29-0.97; P=.04) and 0.61 of developing Alzheimer disease (95% confidence interval, 0.31-1.18; P=.14). Subjects in the upper quartile of plasma PC DHA levels had a mean DHA intake of 0.18 g/d and a mean fish intake of 3.0 servings per week (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.001) in a subset of 488 participants. We found no other significant associations. The top quartile of plasma PC DHA level was associated with a significant 47% reduction in the risk of developing all-cause dementia in the Framingham Heart Study.

Research paper thumbnail of Habitual sleep duration is associated with BMI and macronutrient intake and may be modified by CLOCK genetic variants

by Rozenn Lemaitre, Hassan Dashti, Paul Jacques, Stefania Lamon-fava, Leena Kovanen, Traci Bartz, Mia-maria Perälä, Loukianos Rallidis, Vera Mikkilä, W. Johnson, and Sina Gharib

The American journal of clinical nutrition, 2015

Short sleep duration has been associated with greater risks of obesity, hypertension, diabetes, a... more Short sleep duration has been associated with greater risks of obesity, hypertension, diabetes, and cardiovascular disease. Also, common genetic variants in the human Circadian Locomotor Output Cycles Kaput (CLOCK) show associations with ghrelin and total energy intake. We examined associations between habitual sleep duration, body mass index (BMI), and macronutrient intake and assessed whether CLOCK variants modify these associations. We conducted inverse-variance weighted, fixed-effect meta-analyses of results of adjusted associations of sleep duration and BMI and macronutrient intake as percentages of total energy as well as interactions with CLOCK variants from 9 cohort studies including up to 14,906 participants of European descent from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. We observed a significant association between sleep duration and lower BMI (β ± SE = 0.16 ± 0.04, P < 0.0001) in the overall sample; however, associations between sl...

Research paper thumbnail of Comparing fluorescence-based cell-free assays for the assessment of antioxidative capacity of high-density lipoproteins

Lipids in health and disease, Jan 22, 2016

Population studies have shown an inverse association between high-density lipoprotein (HDL) chole... more Population studies have shown an inverse association between high-density lipoprotein (HDL) cholesterol levels and risk of coronary heart disease (CHD). HDL has different functions, including the ability to protect biological molecules from oxidation. Our aim was to evaluate the performance of two fluorescence-based assays in assessing the antioxidative capacity of HDL. We compared the antioxidative capacity of HDL with the phospholipid 2',7'-dichlorodihydrofluorescein (DCF) assay and the dihydrorhodamine 123 (DHR) assay in controls and in subjects at increased risk of CHD, including subjects with established CHD, and subjects with elevated plasma triglycerides (TG), serum amyloid A (SAA), or myeloperoxidase (MPO) levels. The antioxidative capacity of HDL, as measured by the DCF assay, was significantly lower in both CHD and high-TG patients than in controls (p < 0.001 and p = 0.004, respectively). Interestingly, the mean antioxidative capacity of HDL in high-SAA subjects...

Research paper thumbnail of Effects of oral eicosapentaenoic acid versus docosahexaenoic acid on human peripheral blood mononuclear cell gene expression

Atherosclerosis, Jan 19, 2015

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have beneficial effects on inflammatio... more Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have beneficial effects on inflammation and cardiovascular disease (CVD). Our aim was to assess the effect of a six-week supplementation with either olive oil, EPA, or DHA on gene expression in peripheral blood mononuclear cells (PBMC). Subjects were sampled at baseline and six weeks after receiving either: olive oil 6.0 g/day (n = 16), EPA 1.8 g/day (n = 16), or DHA 1.8 g/day (n = 18). PBMC were subjected to gene expression analysis by microarray with key findings confirmed by quantitative real-time polymerase chain reaction (Q-PCR). Plasma phospholipid EPA increased 3 fold in the EPA group, and DHA increased 63% in the DHA group (both p < 0.01), while no effects were observed in the olive oil group. Microarray analysis indicated that EPA but not DHA or olive oil significantly affected the gene expression in the following pathways: 1) interferon signaling, 2) receptor recognition of bacteria and viruses, 3) G protein sig...

Research paper thumbnail of Gene-Environment Interactions of Circadian-Related Genes for Cardiometabolic Traits

Diabetes care, Jan 17, 2015

Common circadian-related gene variants associate with increased risk for metabolic alterations in... more Common circadian-related gene variants associate with increased risk for metabolic alterations including type 2 diabetes. However, little is known about whether diet and sleep could modify associations between circadian-related variants (CLOCK-rs1801260, CRY2-rs11605924, MTNR1B-rs1387153, MTNR1B-rs10830963, NR1D1-rs2314339) and cardiometabolic traits (fasting glucose [FG], HOMA-insulin resistance, BMI, waist circumference, and HDL-cholesterol) to facilitate personalized recommendations. We conducted inverse-variance weighted, fixed-effect meta-analyses of results of adjusted associations and interactions between dietary intake/sleep duration and selected variants on cardiometabolic traits from 15 cohort studies including up to 28,190 participants of European descent from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We observed significant associations between relative macronutrient intakes and glycemic traits and short sleep duration (<7 h...

Research paper thumbnail of Clock Genes Explain a Large Proportion of Phenotypic Variance in Systolic Blood Pressure and This Control Is Not Modified by Environmental Temperature

American journal of hypertension, Jan 4, 2015

Diurnal variation in blood pressure (BP) is regulated, in part, by an endogenous circadian clock;... more Diurnal variation in blood pressure (BP) is regulated, in part, by an endogenous circadian clock; however, few human studies have identified associations between clock genes and BP. Accounting for environmental temperature may be necessary to correct for seasonal bias. We examined whether environmental temperature on the day of participants' assessment was associated with BP, using adjusted linear regression models in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) (n = 819) and the Boston Puerto Rican Health Study (BPRHS) (n = 1,248) cohorts. We estimated phenotypic variance in BP by 18 clock genes and examined individual single-nucleotide polymorphism (SNP) associations with BP using an additive genetic model, with further consideration of environmental temperature. In GOLDN, each additional 1 °C increase in environmental temperature was associated with 0.18mm Hg lower systolic BP [SBP; β ± SE = -0.18±0.05mm Hg; P = 0.0001] and 0.10mm Hg lower diastolic BP [DBP; ...

Research paper thumbnail of Docosahexaenoic acid differentially affects TNFα and IL-6 expression in LPS-stimulated RAW 264.7 murine macrophages

Prostaglandins, Leukotrienes and Essential Fatty Acids (PLEFA), 2015

Docosahexaenoic acid (DHA) is generally reported to have anti-inflammatory properties, however, p... more Docosahexaenoic acid (DHA) is generally reported to have anti-inflammatory properties, however, prior work has documented differential effects on individual pro-inflammatory cytokines: reduced IL-6, but not TNFα, mRNA expression in macrophages. To elucidate the mechanism, the roles of prostaglandin E 2 (PGE 2 ), cyclic AMP response element-binding protein (CREB), and NFκB were examined in RAW 264.7 macrophages. DHA did not influence CREB activity, but significantly reduced PGE 2 production by 41% and NFκB activity by 32%. Exogenous PGE 2 inhibited TNFα mRNA expression dose dependently. Unexpectedly, inhibiting PGE 2 production with NS-398 also decreased TNFα mRNA expression, suggesting a concentration-dependent dual role of PGE 2 in regulating TNFα expression. IL-6 expression was unaffected by endogenous or exogenous PGE 2 . Partial block of NFκB activation (SN50; 46%, or, BAY-11-7082; 41%) lowered IL-6 to a greater extent than TNFα mRNA expression. The differential effect of DHA on TNFα and IL-6 mRNA expression may be mediated via reduction in NFκB activity.

Research paper thumbnail of Association between statin use and serum cholesterol concentrations is modified by whole-grain consumption: NHANES 2003-2006

The American journal of clinical nutrition, 2014

Statins are used to lower cardiovascular disease risk in part because of their effects on plasma ... more Statins are used to lower cardiovascular disease risk in part because of their effects on plasma lipid profiles. Dietary whole grains have been reported to improve plasma lipid profiles. Little is known about potential interactions between statins and whole grains. We aimed to assess the interaction between statin use and whole-grain intake in relation to serum lipid concentrations in adults. In this cross-sectional study, we used data from 4284 adults aged ≥45 y with reliable and complete dietary data who were participating in the NHANES 2003-2006. Usual whole-grain intake was estimated from two 24-h diet recalls by using the MyPyramid Equivalents Database. Participants self-reported statin use. Total cholesterol and HDL-cholesterol concentrations were measured in all adult participants. The non-HDL-cholesterol concentration and total cholesterol:HDL-cholesterol ratio were calculated. Multiple linear and logistic regression models were used for analyses. Statin usage was 24.9% in a...

Research paper thumbnail of Serotonin transporter polymorphisms and adverse effects with fluoxetine treatment

The short (S) allele of the serotonin transporter gene-linked polymorphic region (5HTTLPR) has be... more The short (S) allele of the serotonin transporter gene-linked polymorphic region (5HTTLPR) has been associated with poorer antidepressant response in major depressive disorder (MDD) and with antidepressant-induced mania. This study investigated a possible association with treatment-emergent insomnia or agitation. Methods: Thirty-six outpatients with MDD were genotyped at 5HTTLPR and treated with open-label fluoxetine up to 60 mg/day. Treatment-emergent adverse effects were assessed at each study visit. Results: Of nine subjects homozygous for the "S" allele, seven (78%) developed new or worsening insomnia, versus 6 of 27 (22%) non-"S"-homozygous subjects (Fisher's exact p ϭ .005). Similarly, six of nine subjects homozygous for the "S" allele (67%) developed agitation, versus 2 of 27 (7%) of non-"S"-homozygous subjects (Fisher's exact p ϭ .001). Conclusions: The "S" allele of the 5HTTLPR may identify patients at risk for developing insomnia or agitation with fluoxetine treatment. This preliminary result requires confirmation in larger samples.

Research paper thumbnail of Dietary modulators of statin efficacy in cardiovascular disease and cognition

Molecular Aspects of Medicine, 2014

Research paper thumbnail of Buspirone Therapy for Type A Behavior, Hostility, and Perceived Stress in Cardiac Patients

Psychotherapy and Psychosomatics, 1993

Hostility is considered to be a risk factor for coronary artery disease. Despite the findings of ... more Hostility is considered to be a risk factor for coronary artery disease. Despite the findings of reduced serotonergic function and effectiveness of treatment with serotonergic agents in similar symptom complexes, there have been no attempts at using serotonergic psychopharmacologic agents to treat this population. We conducted an 8-week open trial of 10 type A, irritable men with coronary artery disease and no diagnosable psychiatric (axis I) condition to examine the effects of buspirone on these subjects. Buspirone appears to significantly reduce type A behavior, hostility, anxiety, impatience, and perceived stress.

Research paper thumbnail of Effects of estrogen replacement on plasma lipoproteins and apolipoproteins in postmenopausal, dyslipidemic women

Metabolism, 1992

The effects of oral estrogen replacement (ethinyl estradiol 0.02 mg/d) on plasma triglyceride, to... more The effects of oral estrogen replacement (ethinyl estradiol 0.02 mg/d) on plasma triglyceride, total cholesterol, very-lowdensity lipoprotein (VLDL) cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and apolipoprotein (apo) A-l and B levels and LDL particle size were assessed in 20 postmenopausal women with a previous hysterectomy and various forms of dyslipidemia (LDL cholesterol L 4.14 mmol/L [160 mg/dL] and/or HDL cholesterol s 1.03 mmol/L (40 mg/dL]). All subjects were studied while on a standard cholesterol-lowering diet, and were sampled in the fasting state before beginning estrogen therapy and after a mean of 13 weeks of estrogen therapy. Lipids were measured by standardized enzymatic techniques, apos were measured by enzyme-linked immunoassays, and LDL particle size was measured by gradient gel electrophoresis. Mean values for plasma lipid parameters (mmol/L) at baseline and during estrogen replacement were as follows: triglyceride, 2.11 and 2.75 (30% increase); total cholesterol, 7.45 and 6.52 (13% decrease); VLDL cholesterol, 1.09 and 1.22 (12% increase); LDL cholesterol, 5.09 and 3.70 (27% decrease); and HDL cholesterol, 1.27 and 1.56 (24% increase). Mean values for apo A-l were 163 and 254 mg/dL (56% increase), and for apo B they were 170 and 148 mg/dL (13% decrease). The LDL particle score was 4.09 and 4.52 (11% smaller). Changes in all parameters were statistically significant (P = .05) except for VLDL cholesterol. These data indicate that estrogen replacement is effective in decreasing LDL cholesterol and apo B concentrations and increasing HDL cholesterol and apo A-l concentrations in dyslipidemic postmenopausal women, but it should not be used in patients with baseline fasting triglyceride levels higher than 2.82 mmol/ L (250 mg/dL) unless it is accompanied by a progestin. Our data indicate that this form of estrogen replacement could lower the risk of coronary artery disease (CAD) by more than 50% in these women, based on favorable alterations in plasma lipoproteins.

Research paper thumbnail of Physiologic benefits of a stress reduction program for healthy middle-aged army officers

Journal of Psychosomatic Research, 1993

Stress reduction programs (SRPs) can reduce morbidity and mortality in patients with coronary art... more Stress reduction programs (SRPs) can reduce morbidity and mortality in patients with coronary artery disease (CAD). This study evaluated the effect of an SRP on metabolic and hormonal risk factors for CAD. Twenty army officers participating in an SRP, Group I, and a comparison group of seventeen SRP nonparticipants, Group C, volunteered to undergo measurement of dehydroepiandrosterone-sulfate (DHEA-S), cortisol, DHEA-S/cortisol ratio, testosterone, apolipoprotein-A1, apolipoprotein-B, triglycerides, cholesterol, fibrinogen, and leukocyte count both before and after the SRP period. No differences in the changes in biochemical risk factors for CAD were found between participant and nonparticipant except for DHEA-S. While Group C had a marked reduction in DHEA-S levels, Group I had a small increase. Previous studies indicate DHEA-S is inversely associated with extent of CAD and age-adjusted DHEA-S levels below 3.78 mumol/l confer an increased risk for CAD mortality. SRP participation appears to effect DHEA-S levels, possibly partially accounting for the benefits observed in SRPs among CAD patients.

Research paper thumbnail of Association of polymorphisms in genes involved in lipoprotein metabolism with plasma concentrations of remnant lipoproteins and HDL subpopulations before and after hormone therapy in postmenopausal women

Clinical Endocrinology, 2010

Objective-A high degree of inter-individual variability in plasma lipid level response to hormone... more Objective-A high degree of inter-individual variability in plasma lipid level response to hormone therapy (HT) has been reported. Variations in the oestrogen receptor α gene (ESR1) and in genes involved in lipid metabolism may explain some of the variability in response to HT.

Research paper thumbnail of Adiponectin: An independent risk factor for coronary heart disease in men in the Framingham offspring Study

Atherosclerosis, 2011

Objective: Our aim was to determine whether plasma adiponectin levels were an independent predict... more Objective: Our aim was to determine whether plasma adiponectin levels were an independent predictor of coronary heart disease (CHD) risk. Methods and results: Plasma adiponectin levels were measured in 3188 male and female participants from cycle 6 of the Framingham offspring Study (mean age: 57 years in both men and women; BMI: 28.5 kg/m 2 in men and 27.3 kg/m 2 in women), using a novel fully automated assay. Plasma adiponectin levels (median [25th percentile, 75th percentile]) were significantly higher in female than in male CHDfree subjects (14.8 [10.7,20.5] g/ml versus 9.0 [7.0,12.2] g/ml, p < 0.001). Participants were followed for a mean of 7.5 years. After adjustment for age, BMI, smoking status, systolic blood pressure, treatment for hypertension, diabetes, use of cholesterol-lowering medication, total cholesterol level, high-density lipoprotein cholesterol level, and C-reactive protein levels, a higher plasma adiponectin level was a significant predictor of lower risk of future CHD events (n = 117) in men (HR 0.49, p < 0.0022). A similar trend was observed in women, but was no longer significant after multivariate adjustments. Conclusions: Our data indicate that plasma adiponectin levels are an independent predictor of CHD in Caucasian men initially free of CHD.

Research paper thumbnail of Apolipoprotein B metabolism in humans: studies with stable isotope-labeled amino acid precursors

Atherosclerosis, 2002

This article reviews the literature from 1986 to early 2001 relating to apoB100 and apoB48 kineti... more This article reviews the literature from 1986 to early 2001 relating to apoB100 and apoB48 kinetics in humans using amino acid precursors labeled with stable isotopes. The following subjects are reviewed: (1) methodology; (2) normal individuals and the effects of aging; (3) diet; (4) hereditary dyslipidemias: familial hypercholesterolemia, familial combined hyperlipidemia, cholesteryl ester storage disease, cholesteryl ester transfer protein deficiency, lipoprotein lipase deficiency, familial hypobetalipoproteinemia, and truncated forms of apoB; (5) hormonal perturbations: estrogen, insulin, diabetes, obesity, and growth hormone; (6) the nephrotic syndrome; and (7) the effects of the statin class of drugs. Because of the advances which have been made in mass spectrometry techniques, the advantages of using non-radioactive tracers in humans have made stable isotope kinetic studies the present day standard in this area of research.

Research paper thumbnail of Plasma Phosphatidylcholine Docosahexaenoic Acid Content and Risk of Dementia and Alzheimer Disease

Archives of Neurology, 2006

Docosahexaenoic acid (DHA) is an abundant fatty acid in the brain. In the diet, DHA is found most... more Docosahexaenoic acid (DHA) is an abundant fatty acid in the brain. In the diet, DHA is found mostly in fatty fish. The content of DHA has been shown to be decreased in the brain and plasma of patients with dementia. To determine whether plasma phosphatidylcholine (PC) DHA content is associated with the risk of developing dementia. A prospective follow-up study in 899 men and women who were free of dementia at baseline, had a median age of 76.0 years, and were followed up for a mean of 9.1 years for the development of all-cause dementia and Alzheimer disease. Plasma PC fatty acid levels were measured at baseline. Cox proportional regression analysis was used to assess relative risks of all-cause dementia and Alzheimer disease according to baseline plasma levels. Ninety-nine new cases of dementia (including 71 of Alzheimer disease) occurred during the follow-up. After adjustment for age, sex, apolipoprotein E epsilon4 allele, plasma homocysteine concentration, and education level, subjects in the upper quartile of baseline plasma PC DHA levels, compared with subjects in the lower 3 quartiles, had a relative risk of 0.53 of developing all-cause dementia (95% confidence interval, 0.29-0.97; P=.04) and 0.61 of developing Alzheimer disease (95% confidence interval, 0.31-1.18; P=.14). Subjects in the upper quartile of plasma PC DHA levels had a mean DHA intake of 0.18 g/d and a mean fish intake of 3.0 servings per week (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.001) in a subset of 488 participants. We found no other significant associations. The top quartile of plasma PC DHA level was associated with a significant 47% reduction in the risk of developing all-cause dementia in the Framingham Heart Study.

Research paper thumbnail of Habitual sleep duration is associated with BMI and macronutrient intake and may be modified by CLOCK genetic variants

by Rozenn Lemaitre, Hassan Dashti, Paul Jacques, Stefania Lamon-fava, Leena Kovanen, Traci Bartz, Mia-maria Perälä, Loukianos Rallidis, Vera Mikkilä, W. Johnson, and Sina Gharib

The American journal of clinical nutrition, 2015

Short sleep duration has been associated with greater risks of obesity, hypertension, diabetes, a... more Short sleep duration has been associated with greater risks of obesity, hypertension, diabetes, and cardiovascular disease. Also, common genetic variants in the human Circadian Locomotor Output Cycles Kaput (CLOCK) show associations with ghrelin and total energy intake. We examined associations between habitual sleep duration, body mass index (BMI), and macronutrient intake and assessed whether CLOCK variants modify these associations. We conducted inverse-variance weighted, fixed-effect meta-analyses of results of adjusted associations of sleep duration and BMI and macronutrient intake as percentages of total energy as well as interactions with CLOCK variants from 9 cohort studies including up to 14,906 participants of European descent from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. We observed a significant association between sleep duration and lower BMI (β ± SE = 0.16 ± 0.04, P < 0.0001) in the overall sample; however, associations between sl...