Higher Baseline Cholesterol Research Articles

Lipophilic statins in cognitively normal subjects: Associations with conversion to mild cognitive impairment in a long‐term longitudinal multi‐center study

AbstractBackgroundStudies of the relationship between the use of statins (HMG‐CoA reductase inhibitors) and subsequent cognitive performance have been variously reported to demonstrate beneficial, harmful, or no significant effects. We aimed to help clarify the relationship between statin use and long‐term trajectory in subjects cognitively normal at baseline, comparing users of statins with known moderate (atorvastatin) or high (simvastatin) lipophilicity and blood‐brain barrier penetrance (LS), to non‐users (nonS), or users of other statins (OS).MethodFrom a consecutive series of 2305 subjects enrolled in the Alzheimer’s Disease Neuroimaging Initiative, 69 were excluded for taking combination statin drugs. Excluding statin users with less than 66 months of usage resulted in 340 CN subjects ( 189 nonS, 121 LS, and 30 OS) who were further studied. Subjects were stratified into groups with low (<175mg/dl), medium (175‐207mg/dl), or high ( ≥207mg/dl) baseline cholesterol levels. The significance of differential conversion rates was assessed by Chi‐Squared tests for homogeneity. Survival trajectories were created using the Kaplan‐Meier method, where an event was defined as conversion to mild cognitive impairment (MCI), and the significance of difference was assessed by the log‐rank test.ResultWhile serum cholesterol levels at baseline ranged widely (112‐174 mg/dl), among 112 subjects with low baseline cholesterol, levels did not significantly differ between those who did convert to MCI within 72 months (157 mg/dl) vs. those who did not (155 mg/dl), but their rates of conversion to MCI significantly differed according to LS use: 39.5% among LS vs. 14.8% among nonS+OS converted (p=0.025). The 6‐year event‐free survival of the nonS+OS group (88.7%; 95% CI 0.785‐1) and the LS group (64.0%; 95% CI 0.519‐0.789) also differed significantly (p=0.019). LS usage was associated with an increased absolute (+24.7%) and relative (+167%) risk.ConclusionLipophilic statin use was associated with more than double the risk of declining to MCI over 72 months of follow‐up in cognitively normal patients with low baseline cholesterol. In separate analyses, no such risk was observed among other statin users, nor among subjects with medium or high baseline cholesterol levels.

Association of dietary lipid intake with low-density lipoprotein cholesterol levels: analysis of two independent population-based studies.

Serum low-density lipoprotein cholesterol (LDL-C) concentration is associated with the risk of cardiovascular disease. However, whether cholesterol and fat intake independently affect serum LDL-C levels remains controversial. We aimed to explore the differential effects of dietary cholesterol and fats on blood lipid profiles according to the presence of dyslipidemia. A cross-sectional study was conducted based on data from the sixth Korean National Health and Nutrition Examination Survey (2013-2015), and a prospective cohort study was conducted using data from the Korean Genome Epidemiology Study. The analyses used data from 10,068 adults and from 9652 adults, respectively. Adjusted mean values of blood lipids were calculated according to cholesterol and fat intake using analysis of covariance. A repeated-measures covariance pattern linear mixed model with unstructured covariance within participants was used to examine longitudinal associations between cholesterol intake and serum concentrations of total cholesterol and LDL-C. Substitutional analysis was conducted to estimate carbohydrate substitution with saturated fat or unsaturated fat. Serum LDL-C level was significantly higher in dyslipidemic subjects who consumed more than 300mg cholesterol per day than in those who consumed less than 300mg cholesterol per day. At a mean 9-year follow-up, levels of total cholesterol and LDL-C were significantly higher in dyslipidemic individuals with higher baseline cholesterol intake after adjustment for potential confounders. In regard to dietary fats, replacing carbohydrate with unsaturated fat was associated with lower level of LDL-C in subjects with dyslipidemia. Serum LDL-C is associated with the intake of dietary cholesterol, especially in individuals with dyslipidemia.

Impact of Foods and Dietary Supplements Containing Hydroxycinnamic Acids on Cardiometabolic Biomarkers: A Systematic Review to Explore Inter-Individual Variability.

Plant-based diets rich in bioactive compounds such as polyphenols have been shown to positively modulate the risk of cardiometabolic (CM) diseases. The inter-individual variability in the response to these bioactives may affect the findings. This systematic review aimed to summarize findings from existing randomized clinical trials (RCTs) evaluating the effect of hydroxycinnamic acids (HCAs) on markers of CM health in humans. Literature searches were performed in PubMed and the Web of Science. RCTs on acute and chronic supplementation of HCA-rich foods/extracts on CM biomarkers were included. Forty-four RCTs (21 acute and 23 chronic) met inclusion criteria. Comparisons were made between RCTs, including assessments based on population health status. Of the 44 RCTs, only seven performed analyses on a factor exploring inter-individual response to HCA consumption. Results demonstrated that health status is a potentially important effect modifier as RCTs with higher baseline cholesterol, blood pressure and glycaemia demonstrated greater overall effectiveness, which was also found in studies where specific subgroup analyses were performed. Thus, the effect of HCAs on CM risk factors may be greater in individuals at higher CM risk, although future studies in these populations are needed, including those on other potential determinants of inter-individual variability. PROSPERO, registration number CRD42016050790.

Efficacy and tolerability of lamivudine plus dolutegravir compared with lamivudine plus boosted PIs in HIV-1 positive individuals with virologic suppression: a retrospective study from the clinical practice

BackgroundDirect comparisons between lamivudine plus bPIs and lamivudine plus dolutegravir as maintenance strategies in virologically-suppressed HIV positive patients are lacking.MethodsTime to treatment discontinuation (TD) and virological failure (VF) were compared in a cohort of HIV+ patients on a virologically-effective ART starting lamivudine with either darunavir/r, atazanavir/r or dolutegravir. Changes in laboratory parameters were also evaluated.ResultsFour-hundred-ninety-four patients were analyzed (170 switching to darunavir/r, 141 to atazanavir/r, 183 to dolutegravir): median age was 49 years, with 8 years since ART start. Groups differed for age, HIV-risk factor, time since HIV-diagnosis and on ART, previous therapy and reasons for switching.Estimated proportions free from TD at week 48 and 96 were 79.8 and 48.3% of patients with darunavir/r, 87.0 and 70.9% with atazanavir/r, and 88.2 and 82.6% with dolutegravir, respectively (p < 0.001). Calendar years, HIV-risk factor, higher baseline cholesterol and an InSTI-based previous regimen predicted TD, whereas lamivudine+dolutegravir therapy and previous tenofovir use were protective. VF was the cause of TD in 6/123 cases with darunavir/r, 4/97 with atazanavir/r and 3/21 with dolutegravir. Other main reasons for TD were: toxicity (43.1% with darunavir/r, 39.2% with atazanavir/r, 52.4% with dolutegravir), further simplification (36.6% with darunavir/r, 30.9% with atazanavir/r, 14.3% with dolutegravir). Incidence of VF did not differ among study groups (p = 0.747). No factor could predict VF.Lipid profile improved in the dolutegravir group, whereas renal function improved in the bPIs groups.ConclusionsIn real practice, a switch to lamivudine+dolutegravir showed similar efficacy but longer durability than a switch to lamivudine+bPIs.

Addition of milk fat globule membrane-enriched supplement to a high-fat meal attenuates insulin secretion and induction of soluble epoxide hydrolase gene expression in the postprandial state in overweight and obese subjects.

CVD and associated metabolic diseases are linked to chronic inflammation, which can be modified by diet. The objective of the present study was to determine whether there is a difference in inflammatory markers, blood metabolic and lipid panels and lymphocyte gene expression in response to a high-fat dairy food challenge with or without milk fat globule membrane (MFGM). Participants consumed a dairy product-based meal containing whipping cream (WC) high in saturated fat with or without the addition of MFGM, following a 12 h fasting blood draw. Inflammatory markers including IL-6 and C-reactive protein, lipid and metabolic panels and lymphocyte gene expression fold changes were measured using multiplex assays, clinical laboratory services and TaqMan real-time RT-PCR, respectively. Fold changes in gene expression were determined using the Pfaffl method. Response variables were converted into incremental AUC, tested for differences, and corrected for multiple comparisons. The postprandial insulin response was significantly lower following the meal containing MFGM (P < 0·01). The gene encoding soluble epoxide hydrolase (EPHX2) was shown to be more up-regulated in the absence of MFGM (P = 0·009). Secondary analyses showed that participants with higher baseline cholesterol:HDL-cholesterol ratio (Chol:HDL) had a greater reduction in gene expression of cluster of differentiation 14 (CD14) and lymphotoxin β receptor (LTBR) with the WC+MFGM meal. The protein and lipid composition of MFGM is thought to be anti-inflammatory. These exploratory analyses suggest that addition of MFGM to a high-saturated fat meal modifies postprandial insulin response and offers a protective role for those individuals with higher baseline Chol:HDL.

Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment.

Familial hypercholesterolaemia (FH) is a common genetic cause of premature coronary heart disease (CHD). Globally, one baby is born with FH every minute. If diagnosed and treated early in childhood, individuals with FH can have normal life expectancy. This consensus paper aims to improve awareness of the need for early detection and management of FH children. Familial hypercholesterolaemia is diagnosed either on phenotypic criteria, i.e. an elevated low-density lipoprotein cholesterol (LDL-C) level plus a family history of elevated LDL-C, premature coronary artery disease and/or genetic diagnosis, or positive genetic testing. Childhood is the optimal period for discrimination between FH and non-FH using LDL-C screening. An LDL-C ≥5 mmol/L (190 mg/dL), or an LDL-C ≥4 mmol/L (160 mg/dL) with family history of premature CHD and/or high baseline cholesterol in one parent, make the phenotypic diagnosis. If a parent has a genetic defect, the LDL-C cut-off for the child is ≥3.5 mmol/L (130 mg/dL). We recommend cascade screening of families using a combined phenotypic and genotypic strategy. In children, testing is recommended from age 5 years, or earlier if homozygous FH is suspected. A healthy lifestyle and statin treatment (from age 8 to 10 years) are the cornerstones of management of heterozygous FH. Target LDL-C is <3.5 mmol/L (130 mg/dL) if >10 years, or ideally 50% reduction from baseline if 8–10 years, especially with very high LDL-C, elevated lipoprotein(a), a family history of premature CHD or other cardiovascular risk factors, balanced against the long-term risk of treatment side effects. Identifying FH early and optimally lowering LDL-C over the lifespan reduces cumulative LDL-C burden and offers health and socioeconomic benefits. To drive policy change for timely detection and management, we call for further studies in the young. Increased awareness, early identification, and optimal treatment from childhood are critical to adding decades of healthy life for children and adolescents with FH.

Incidence, Impact, and Predictors of Cranial Nerve Palsy and Haematoma Following Carotid Endarterectomy in the International Carotid Stenting Study

ObjectiveCranial nerve palsy (CNP) and neck haematoma are complications of carotid endarterectomy (CEA). The effects of patient factors and surgical technique were analysed on the risk, and impact on disability, of CNP or haematoma in the surgical arm of the International Carotid Stenting Study (ICSS), a randomized controlled clinical trial of stenting versus CEA in patients with symptomatic carotid stenosis.Materials and methodsA per-protocol analysis of early outcome in patients receiving CEA in ICSS is reported. Haematoma was defined by the surgeon. CNP was confirmed by an independent neurologist. Factors associated with the risk of CNP and haematoma were investigated in a binomial regression analysis.ResultsOf the patients undergoing CEA, 45/821 (5.5%) developed CNP, one of which was disabling (modified Rankin score = 3 at 1 month). Twenty-eight (3.4%) developed severe haematoma. Twelve patients with haematoma also had CNP, a significant association (p < .01). Independent risk factors modifying the risk of CNP were cardiac failure (risk ratio [RR] 2.66, 95% CI 1.11 to 6.40), female sex (RR 1.80, 95% CI 1.02 to 3.20), the degree of contralateral carotid stenosis, and time from randomization to treatment >14 days (RR 3.33, 95% CI 1.05 to 10.57). The risk of haematoma was increased in women, by the prescription of anticoagulant drugs pre-procedure and in patients with atrial fibrillation, and was decreased in patients in whom a shunt was used and in those with a higher baseline cholesterol level.ConclusionsCNP remains relatively common after CEA, but is rarely disabling. Women should be warned about an increased risk. Attention to haemostasis might reduce the incidence of CNP. ICSS is a registered clinical trial: ISRCTN 25337470.

The impact of maternal obesity and gestational weight gain on early and mid‐pregnancy lipid profiles

ObjectiveWe evaluated the impact of maternal overweight/obesity and excessive weight gain on maternal serum lipids in the first and second trimester of pregnancy.Design and MethodsProspective data were collected for 225 women. Maternal serum lipids and fatty acids were measured at <13 weeks and between 24–28 weeks. Analyses were stratified by normal weight versus overweight/obese status and excessive vs. non-excessive weight gain.ResultsOverweight/obese women had higher baseline cholesterol (161.3±29.6 vs 149.4±26.8 mg/dL, p<0.01), LDL (80.0±19.9 vs 72.9 ±18.8 mg/dL, p<0.01) and triglycerides ( 81.7±47.2 vs 69.7±40.3 mg/dL, p=0.05) when compared to normal weight women, while HDL (43.6 ±10.4 47.6±11.5 mg/dL, p<0.01) was lower. However, cholesterol and LDL increased at a higher weekly rate in normal weight women, resulting in higher total cholesterol in normal weight women (184.1±28.1 vs. 176.0 ±32.1 mg/dL, p=0.05) at 24–28 weeks. Excessive weight gain did not affect the rate of change in lipid profiles in either group. Overweight/obese women had higher levels of arachidonic acid at both time points.ConclusionsOverweight/obese women have significantly more atherogenic lipid profiles than normal weight women during the period of early pregnancy, delineating one physiologic pathway that could explain differences in pregnancy outcomes between normal weight and overweight/obese women.

The markers predicting response to Hepatitis C virus treatment and evaluation of treatment responses

Objectives: Currently pegylated interferon alpha (peg-IFN) and ribavirin treatment is recommended for chronic hepatitis C treatment. The aim of treatment is to provide sustained viral response (SVR). Material and methods: A total of 125 patients, who have been treated for chronic hepatitis C diagnosis and are followed up until 6 months after treatment, were enrolled into the study. Markers, which have indicated treatment response against hepatitis C virus treatment, treatment responses according to peg-IFNα type used, and experienced side effects in patients have been compared. Results: Of patients, 103 were (82.4%) female and 22 were (17.6%) male and mean of age was 54.74±7.93 years. Markers indicating SVR in our study were calculated as rapid viral response (RVR) (p 2) (p<0.034). Predictive parameters for EVR in our study were defined as absence of diabetes in patients, high baseline lymphocyte numbers (2024.74±625.93) and high baseline cho lesterol level (in EVR positive patients 180.47±32.77 mg/dl; in EVR negatives 152.00±24.56). There was no statistical difference between peg-IFN type in patients and RVR, EVR and SVR. Also there was no statistical difference in hematological side effects (neutropenia, anemia, and thrombocytopenia) in both treatment groups. Conclusions: As the efficacy of treatment against HCV is defined, predictive markers for the treatment response are becoming more significant. Therefore, it is concluded that these factors should also be considered in patient treatment plans. J Microbiol Infect Dis 2012; 2(3): 100-108

Cholesterinhomöostase und kardiovaskuläres Risiko

Hypercholesterolemia is a major risk factor for cardiovascular diseases. Serumcholesterol concentrations are regulated by enteral absorption and hepatic synthesis. Statins inhibit the rate-limiting enzyme of endogenous cholesterol synthesis, HMG-CoA-reductase and reduce serum cholesterol concentrations as well as cardiovascular morbidity. Indirect evidence from smaller studies shows, that patients with high baseline cholesterol absorption may show only a small response to statin treatment in terms of cholesterol lowering. Moreover, evidence from recent clinical studies suggests that increased cholesterol absorption and decreased hepatic cholesterol synthesis is associated with an increased cardiovascular risk. This article reviews the current literature on this issue and suggests prospective clinical studies to analyze whether determination of the baseline relation of cholesterol synthesis and absorption may facilitate an individualized lipid lowering therapy to further reduce cardiovascular risk.

Homocysteine-Lowering Therapy and Stroke Risk, Severity, and Disability

Elevated total homocysteine is associated with a higher risk of cerebrovascular disease. It is not known whether lowering homocysteine impacts on stroke risk, both in terms of severity and ischemic vs hemorrhagic stroke subtypes. Our aim was to determine whether vitamin therapy reduces the risk of ischemic and hemorrhagic stroke, as well as stroke-related disability. We analyzed stroke outcomes among participants of the Heart Outcomes Prevention Evaluation 2 (HOPE 2) trial that randomized 5522 adults with known cardiovascular disease to a daily combination of 2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12, or matching placebo, for 5 years. Among 5522 participants, stroke occurred in 258 (4.7%) individuals during a mean of 5 years of follow-up. The geometric mean homocysteine concentration decreased by 2.2 micromol/L in the vitamin therapy group and increased by 0.80 micromol/L in the placebo group. The incidence rate of stroke was 0.88 per 100 person-years in the vitamin therapy group and 1.15 per 100 person-years in the placebo group (hazard ratio [HR], 0.75; 95% CI, 0.59-0.97). Vitamin therapy also reduced the risk of nonfatal stroke (HR, 0.72; 95% CI, 0.54-0.95) but did not impact on neurological deficit at 24 hours (P=0.45) or functional dependence at discharge or at 7 days (OR, 0.95; 95% CI, 0.57-1.56). In subgroup analysis, patients aged younger than 69 years, from regions without folic acid food fortification, with higher baseline cholesterol and homocysteine levels, and those not receiving antiplatelet or lipid-lowering drugs at enrollment had a larger treatment benefit. Lowering of homocysteine with folic acid and vitamins B6 and B12 did reduce the risk of overall stroke, but not stroke severity or disability.

Statins: established indications and controversial subgroups

Statins are, to date, the most powerful cholesterol lowering drugs. In brief, they inhibit 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, which is a key enzyme in the initial chain of the steroid...

The efficacy of vitamin C supplementation on reducing total serum cholesterol in human subjects: a review and analysis of 51 experimental trials

Objective Observational studies in humans have shown an inverse relationship between plasma vitamin C concentration and total serum cholesterol. However, experimental studies have shown inconsistent results regarding the ability of vitamin C to reduce total serum cholesterol. Methods Published reports of trials studying the effects of vitamin C on serum lipids were identified by a search of Medline from 1966 to 2004. Data from 51 experimental studies comprising of 1666 pooled subjects were selected for analysis. Results A very strong negative association was observed between baseline total serum cholesterol and the percent change in cholesterol (r = −0.585, p<0.001). When subjects were divided into 4 groups based on their baseline total serum cholesterol levels, the following weighted mean percent changes in cholesterol from baseline were observed: normal cholesterol (<199mg/dl): 0.91±6.8% (n=508); borderline high cholesterol (200–239mg/dl): 3.90±5.78% (n=605); high cholesterol (240–279mg/dl): 11.40±7.96% (n=300); severe cholesterol (>280mg/dl): 14.30±8.36% (n=253). A significant inverse relationship was found between the baseline plasma vitamin C concentrations and mean percent change in total cholesterol from baseline (r = −0.500, p<0.005). It was also observed that the high and severe baseline cholesterol groups possessed lower baseline plasma vitamin C concentrations than those in the normal cholesterol groups (0.79 and 0.55 versus 1.24 mg/dl respectively). Conclusion This finding strengthens the hypothesis that the cholesterol lowering and cardio-protective benefit of vitamin C supplementation may be in its ability to elevate plasma vitamin C concentrations in those patients who initially possess lower than normal vitamin C plasma concentrations.

Beyond LDL lowering: the role of dyslipidaemia and inflammation

This edition of the British Journal of Diabetes and Vascular Disease is focused on dyslipidaemia, an emerging area of clinical management that is beyond low density lipoprotein (LDL) lowering. The importance of dyslipidaemia as a metabolic feature of type 2 diabetes and the metabolic syndrome may be a key therapeutic target in the future management of patients at high cardiovascular risk. Additionally, two intriguing observations are also discussed in this issue. Firstly, the finding of stroke reduction in the lipid-lowering trials which is presented by Buckley in the review of Lipids and Stroke (see pages 170‐6). The second, covering the emerging role of inflammation in the atherosclerotic process which is covered by Schachter in Lipid lowering drugs, inflammation and cardiovascular disease (see pages 178‐82). Since the 1970s ‐ the era of the first major lipid-lowering drug study ‐ there have been over 20 major randomised trials assessing cholesterol lowering. These trials, which specifically evaluated lipid-lowering drugs as unifactorial risk modification, evaluated their effects on clinical coronary end points (angina, unstable angina, myocardial infarction or revascularisation procedures such as percutaneous transluminal coronary angioplasty or coronary artery bypass graft). Over the same period, the 25 angiographic studies have given details of the changes in the coronary artery lumen following effective cholesterol lowering with diet, drug or surgical interventions. While the majority of trials have used statin drugs all classes of drugs including fibrates, nicotinic acid and bile acid sequestrants have been assessed either in monotherapy or in combination with other lipid-lowering drug therapies. Treatment benefit has been shown in several subgroups including ‐ older compared to younger, low compared to high baseline cholesterol and those at highest coronary heart disease (CHD) risk (e.g. existing CHD), current smoker and diabetes. There is therefore a substantial evidence-base from these randomised intervention trials that the benefit of effective lowering of total- and LDL-cholesterol (LDL-c) is a consistent finding in both the reduction of clinical coronary events and improved coronary angiographic findings. With the accumulation of data from the lipid-lowering trials, several new and important observations have emerged. These findings underscore the key role of other factors besides the level (concentration) of LDL, and includes high density lipoprotein (HDL), compositional (size) changes of LDL and raised serum triglycerides as well as non-lipid factors. Some of these observations may go some way in explaining why treatment has not abolished all new clinical events and thus prevent the epidemic of coronary artery disease (CAD).

Tamoxifen and Cardiac Risk Factors in Healthy Women: Suggestion of an Anti-Inflammatory Effect

-Tamoxifen reduces the incidence of breast cancer in women at risk for that disease. Because heart disease is the leading cause of death in women and because tamoxifen is also associated with venous thrombosis, an improved understanding of the association of tamoxifen with cardiovascular disease risk factors is required. In 111 healthy women at a single center, who were participating in a randomized double-blind breast cancer prevention trial, the 6-month effects of oral tamoxifen (20 mg/d) compared with placebo on factors related to inflammation, hemostasis, and lipids were studied. Tamoxifen was associated with reductions of 26% in median C-reactive protein, 22% in median fibrinogen, and 9% in cholesterol (all P:<0.01 compared with placebo). There were no differences in treatment effects on factor VII coagulant activity, fragment 1-2, and triglycerides. In secondary analyses, the effect of tamoxifen on C-reactive protein was larger in postmenopausal women and in women with higher waist-to-hip ratios. The effect on fibrinogen was larger in women with higher baseline cholesterol. Tamoxifen demonstrated effects on inflammatory markers that were consistent with reduced cardiovascular risk. These findings are in contrast to recent reports of increased C-reactive protein associated with postmenopausal estrogen. The potential for beneficial cardiovascular effects of tamoxifen in healthy women is suggested.

Polyunsaturated fatty acids result in greater cholesterol lowering and less triacylglycerol elevation than do monounsaturated fatty acids in a dose-response comparison in a multiracial study group

Cholesterol-lowering effects of polyunsaturated and monounsaturated fatty acids were compared as they were varied in a reciprocal dose-dependent fashion in the context of a National Cholesterol Education Program (NCEP) Step 1 diet. The study population comprised 63 moderately hypercholesterolemic African American and white men and women. After a 6-wk baseline diet containing 37% of energy from total fat and 15% from saturated fat, participants consumed four diets for 6 wk each, in random order, containing 10% of energy as saturated fatty acids; 3%, 6%, 10%, and 14% of energy as polyunsaturated fatty acids; and 17%, 14%, 10%, and 6% of energy as monounsaturated fatty acids. Dietary cholesterol, fiber, plant sterol, and squalene contents were constant with all four diets. There was a progressive decrease in total (P = 0.028) and low-density-lipoprotein cholesterol (P = 0.184) across the four diets, with the greatest decrease observed in the diet with the highest content of polyunsaturated fatty acids; a small but significant decrease in high-density-lipoprotein (HDL) cholesterol that did not show a trend between the polyunsaturated and monounsaturated diets; and a trend between the four diets in triacylglycerol elevations (P = 0.029), with the smallest increment occurring in the diets highest in polyunsaturates. The magnitude of the cholesterol-lowering response was greater in those with higher baseline cholesterol and less in those who were more obese. The dietary response was similar in both ethnic groups and in both sexes. In conclusion, in an NCEP Step 1 diet containing 30% total fat, with all other known cholesterol-influencing dietary factors held constant, the substitution of polyunsaturated fatty acid for monounsaturated fatty acid from 3% to 14% resulted in a progressive decline in total cholesterol and less triacylglycerol elevations, without effect on HDL cholesterol.