Plasma sitosterol elevations are associated with an increased incidence of coronary events in men: Results of a nested case-control analysis of the Prospective Cardiovascular Münster (PROCAM) study

Assmann, Gerd; Cullen, Paul; Erbey, John R.; Ramey, Dena R.; Kannenberg, Frank; Schulte, Helmut

doi:10.1016/j.numecd.2005.04.001

Cited by 232 publications

(179 citation statements)

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“…Miettinen et al ( 27 ) reported an association between raised plasma phytosterol levels and increased phytosterol content of surgically removed carotid plaques, while Weingärtner et al ( 28 ) showed that consumption of phytosterol-enriched margarine correlated with increased plasma concentrations and tissue deposi- An additional factor that infl uences plasma phytosterolto-cholesterol ratios is statin treatment ( 7,36 ), a reason why statin users were excluded from the analyses. Finally, the plasma sitosterol and campesterol ratios to cholesterol were in the same physiological range as reported in previous studies (9)(10)(11)(12)(13)(14)(15)30 ), strengthening the reliability of our data.…”

Section: Characteristics Of Chd Cases and Matched Controlssupporting

confidence: 89%

“…This is a substantial concern, given that inhibition of cholesterol absorption by gram doses of phytosterols incorporated into various foods is widely used as a nonpharmacological strategy for cholesterol lowering but is associated with increased serum phytosterol concentrations ( 8 ). Results of epidemiological studies have suggested either a direct association between plasma phytosterols and coronary heart disease (CHD) risk (9)(10)(11)(12) or a null ( 13,14 ) and even inverse association ( 15 ).…”

Section: Laboratory Measurementsmentioning

confidence: 99%

“…The controversy on whether raised plasma phytosterols are a CHD risk factor in nonsitosterolemic individuals has been fed by the inconsistent fi ndings of epidemiological studies (9)(10)(11)(12)(13)(14)(15). Other contradictory evidence has been presented recently.…”

Section: Characteristics Of Chd Cases and Matched Controlsmentioning

confidence: 99%

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Phytosterol plasma concentrations and coronary heart disease in the prospective Spanish EPIC cohort

Escurriol

Cofán

Moreno-Iribas

et al. 2010

Journal of Lipid Research

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This article is available online at http://www.jlr.org heart disease in the prospective Spanish EPIC cohort. J. Lipid Res . 2010. 51: 618-624. Supplementary key words plant sterols • sitosterol • campesterol • lathosterol • cholesterol • European Prospective Investigation intoCancer and Nutrition • nested case-control study • cardiometabolic risk • apolipoprotein E Dietary sterols consist of animal-derived cholesterol and plant-derived noncholesterol sterols or phytosterols. Phytosterols are important components of a vegetable-based diet and are particularly abundant in whole grains, nuts, seeds, and oils derived from them. The principal molecular forms are sitosterol and campesterol ( 1 ). These compounds are structurally related to cholesterol but have bulkier and more hydrophobic molecules, which confer them a higher affi nity for intestinal micelles than has cholesterol. Consequently, cholesterol is displaced from micelles, and the amount available for absorption is limited. The phytosterol content of usual diets is similar to that of cholesterol (150 to 450 mg/day), but their intestinal absorption is much less effi cient (see review in Ref.2 ). Because of low absorption and rapid biliary elimination, physiological plasma concentrations of phytosterols are in the order of 10 Ϫ 3 those of cholesterol. Their ratios to cholesterol are accepted as surrogate markers for the effi ciency of cholesterol absorption, while those of the Abstract Phytosterol intake with natural foods, a measure of healthy dietary choices, increases plasma levels, but increased plasma phytosterols are believed to be a coronary heart disease (CHD) risk factor. To address this paradox, we evaluated baseline risk factors, phytosterol intake, and plasma noncholesterol sterol levels in participants of a case control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) Spanish cohort who developed CHD (n = 299) and matched controls (n = 584) who remained free of CHD after a 10 year follow-up. Sitosterol-to-cholesterol ratios increased across tertiles of phytosterol intake ( P = 0.026). HDL-cholesterol level increased, and adiposity measures, cholesterol/HDL ratios, and levels of glucose, triglycerides, and lathosterol, a cholesterol synthesis marker, decreased across plasma sitosterol tertiles ( P < 0.02; all). Compared with controls, cases had nonsignifi cantly lower median levels of phytosterol intake and plasma sitosterol. The multivariable-adjusted odds ratio for CHD across the lowest to highest plasma sitosterol tertile was 0.59 (95% confi dence interval, 0.36-0.97). Associations were weaker for plasma campesterol. The apolipoprotein E genotype was unrelated to CHD risk or plasma phytosterols. The data suggest that plasma sitosterol levels are associated with a lower CHD risk while being markers of a lower cardiometabolic risk in the EPIC-Spain cohort, a population with a high phytosterol intake. -Escurriol,

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Section: Characteristics Of Chd Cases and Matched Controlssupporting

confidence: 89%

Section: Laboratory Measurementsmentioning

confidence: 99%

See 1 more Smart Citation

Phytosterol plasma concentrations and coronary heart disease in the prospective Spanish EPIC cohort

Escurriol

Cofán

Moreno-Iribas

et al. 2010

Journal of Lipid Research

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“…This is implied by observations in patients suffering from sitosterolemia, which suggest that plant sterols are more atherogenic than cholesterol. Also, new data from our group suggest that elevated serum sitosterol concentrations may be a risk factor for CHD (Assmann et al, 2006). This finding indicates that not only pathologically high serum phytosterol concentrations as seen in sitosterolemia but also slightly elevated concentrations might be associated with an increased long-term risk of cardiovascular events.…”

Section: Discussionmentioning

confidence: 74%

“…Concentrations of plant sterols and stanols in serum were measured by gas chromatography-mass spectrometry (GC-MS) as described before (Assmann et al, 2006). For quantitation of campestanol the response factors of sitostanol were used.…”

Section: Concentrations Of Plant Sterols and Stanols In Serummentioning

confidence: 99%

Similar serum plant sterol responses of human subjects heterozygous for a mutation causing sitosterolemia and controls to diets enriched in plant sterols or stanols

et al. 2007

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Objective: We investigated the serum phytosterol responses of heterozygous relatives of sitosterolemia patients to diets enriched in phytosterols or stanols. Design: Randomized double-blind crossover design. Setting: Muenster, Germany. Subjects: Eight heterozygous and 13 control subjects were recruited. One heterozygote and three controls dropped out. Interventions: Seven heterozygotes and 10 controls received daily portions of margarine containing 2 g of plant sterols, 2 g of stanols or a control margarine for 6 weeks each in a randomized order. These phases were intercepted by wash-out periods of 6 weeks each. Results: Compared to the control period, serum phytosterol concentrations increased overall by more than 20% when subjects consumed the plant sterol margarine (F (1,15) ¼ 8.719, P ¼ 0.01), with no significant difference between heterozygotes (mean þ 14.5 (s.d. 17.2) mmol/l, þ 23.0%) and controls ( þ 4.9 (9.9) mmol/l, þ 20.5%; F (1,15) ¼ 2.168, P ¼ 0.162), but decreased when subjects consumed the stanol-enriched margarine (F (1,15) ¼ 12.124, P ¼ 0.003), again to a similar extent in heterozygotes (À34.2 (41.2) mmol/l, À54.2%) and controls (À12.2 (9.2) mmol/l, À50.6%; F (1,15) ¼ 2.729, P ¼ 0.119). The lowest total serum concentrations of cholesterol and phytosterols were seen after the diet enriched in stanols. Serum stanol concentrations increased on this diet, but on a very low level and never exceeded 0.05% of serum cholesterol levels in any subject. Conclusions: Serum phytosterol concentrations increased only moderately in heterozygotes consuming a diet enriched in phytosterols, indicating that they retained considerable capacity to excrete phytosterols even at higher intakes. Sponsorship: Supported by a grant of the Stifterverband für die Deutsche Wissenschaft (project number TS022/12372/2002) to MK.

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Food and Western Disease

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Plasma sitosterol elevations are associated with an increased incidence of coronary events in men: Results of a nested case-control analysis of the Prospective Cardiovascular Münster (PROCAM) study

Cited by 232 publications

References 28 publications

Phytosterol plasma concentrations and coronary heart disease in the prospective Spanish EPIC cohort

Phytosterol plasma concentrations and coronary heart disease in the prospective Spanish EPIC cohort

Similar serum plant sterol responses of human subjects heterozygous for a mutation causing sitosterolemia and controls to diets enriched in plant sterols or stanols

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