Naturally-occurring phytosterols in the usual diet influence cholesterol metabolism in healthy subjects.

BACKGROUND AND AIMS: Modulation of cholesterol absorption is potentially an effective way of lowering blood cholesterol levels and decreasing inherent cardiovascular risk in the general population. It is well established that cholesterol absorption efficiency can be modified by the intake of foods enriched with gram-doses of phytosterols, but little is known about the effects of phytosterols in the usual diet, even though moderate doses have been reported to affect whole-body cholesterol metabolism. A way to indirectly measure cholesterol synthesis and absorption rates is by quantification of serum non-cholesterol sterols. The aim of this study was to investigate the role of naturally occurring phytosterol intake on cholesterol absorption and serum cholesterol concentrations in a Spanish free-living population. METHODS AND RESULTS: A total of 85 healthy volunteers were studied regarding their dietary habits (using a validated food frequency questionnaire), lipid profile and surrogate markers of cholesterol metabolism. Subjects were classified into tertiles of total phytosterol intake, and differences in lipid profile and markers of cholesterol metabolism were assessed by multivariate linear regression models adjusted for various confounders. The estimated daily intake of phytosterols and cholesterol was 489 (median) and 513 (mean) mg, respectively. Both serum low-density lipoprotein (LDL)-cholesterol concentration and sitosterol-to-cholesterol ratio adjusted by sitosterol intake (a surrogate marker of intestinal cholesterol absorption) decreased significantly (p < 0.05, both) across tertiles of phytosterol intake. CONCLUSION: Moderate doses of phytosterols in the habitual diet might have a protective effect on the lipid profile via decreasing cholesterol absorption.

SEA 2022 Standards for Global Control of Cardiovascular Risk. / Estándares SEA 2022 para el control global del riesgo cardiovascular.

One of the objectives of the Spanish Society of Arteriosclerosis is to contribute to better knowledge of vascular disease, its prevention and treatment. It is well known that cardiovascular diseases are the leading cause of death in our country and entail a high degree of disability and health care costs. Arteriosclerosis is a multifactorial disease and therefore its prevention requires a global approach that takes into account the different risk factors with which it is associated. Therefore, this document summarizes the current level of knowledge and includes recommendations and procedures to be followed in patients with established cardiovascular disease or at high vascular risk. Specifically, this document reviews the main symptoms and signs to be evaluated during the clinical visit, the laboratory and imaging procedures to be routinely requested or requested for those in special situations. It also includes vascular risk estimation, the diagnostic criteria of the different entities that are cardiovascular risk factors, and makes general and specific recommendations for the treatment of the different cardiovascular risk factors and their final objectives. Finally, the document includes aspects that are not usually referenced in the literature, such as the organization of a vascular risk consultation.

A presumptive new locus for autosomal dominant hypercholesterolemia mapping to 8q24.22.

Molecular testing of patients with autosomal dominant hypercholesterolemia (ADH) fails to detect a causal functional mutation in 15.25% of subjects. We studied an ADH pedigree in which known ADH-causing genes (LDLR, APOB and PCSK9) were excluded. Genome-wide analysis on 15 family members detected significant association for ADH and dbSNP RS ID rs965814 (G/A), located in 8q24.22 cytoband. ADH was significantly associated to rs965814 G allele (p < 0.05) in a case-control study based on 200 unrelated ADH subjects without LDLR or APOB gene defects and 198 normolipidemic controls. We chose 24 markers for a detailed analysis of 8q24.22 cytoband, now based on an extended set of family members (21 individuals). One particular 24 marker haplotype was significantly associated to both higher total and low-density lipoprotein-cholesterol concentrations. Similar results were found for a shorter haplotype, composed of the distal six markers from the complete haplotype. Therefore, a presumptive new locus for ADH could be located in 8q24.22 cytoband, a region not previously linked or associated to ADH.

Role of naturally-occurring plant sterols on intestinal cholesterol absorption and plasmatic levels.

Cardiovascular disease is a major health problem in developed countries although its incidence is relatively lower in Mediterranean countries which is partly ascribed to dietary habits. Epidemiologic evidence shows that elevated serum cholesterol, specifically low-density lipoprotein cholesterol (c-LDL), increases cardiovascular disease. Phytosterols are bioactive compounds, found in all vegetable foods, which inhibit intestinal cholesterol absorption and, therefore, have a serum cholesterol-lowering effect. Intestinal cholesterol absorption is a multistep process where plant sterols and stanols may act: a) attenuating the NPC1L1 gene expression, which may result in a lower cholesterol uptake from the lumen; b) lowering the cholesterol esterification rate by the ACAT2 (acyl-CoA cholesterol acyltransferase) and, consequently, the amount of cholesterol secreted via the chylomicrons and c) upregulating the expression of ABC-transporters ABCG5 and ABCG8 in intestinal cells, which may result in an increased excretion of cholesterol by the enterocyte back into the lumen. Many clinical trials proved that commercial products enriched with phytosterols reduce cholesterol levels. Likewise, recent studies show that phytosterols present in natural food matrices are also effective and could be an important component of cardioprotective dietary patterns such as the Mediterranean diet.

A moderate intake of phytosterols from habitual diet affects cholesterol metabolism.

Cholesterol metabolism homeostasis is the result of a balance between synthesis, degradation and intestinal absorption. It is well established that intestinal cholesterol absorption efficiency can be modified by the intake of phytosterol-enriched food and, therefore, have a serum cholesterol-lowering effect. Recent epidemiological and clinical studies have shown that presence of phytosterols at normal diet levels could also be effective on lowering total and LDL serum cholesterol since they affect whole-body cholesterol metabolism even at those moderate doses. The aim of this study was to analyze the effect of the levels of the naturally-occurring phytosterols in the diet on cholesterol metabolism parameters. In order to do that a group of 99 healthy volunteers was studied for their dietary habits and surrogate markers of cholesterol synthesis and absorption. The mean daily dietary intake of phytosterols, measured by a food semiquantitative frequency questionnaire, was found to be 494 mg being beta-sitosterol the major contributor to it. Subjects were classified into tertiles according to their total phytosterol intake and comparisons were done between subgroups. No statistical differences were observed for surrogate markers of intestinal cholesterol absorption, but a significant increase in the cholesterol synthesis surrogate marker lathosterol-to-cholesterol ratio associated to highest dietary phytosterol intake was observed. Regardless of this, only a non significant trend toward a less atherogenic lipid profile was observed in the upper tertile. In conclusion, the intake of moderate amounts of phytosterols naturally present in habitual diet may affect cholesterol metabolism and specially the rate of cholesterol synthesis as estimated by the surrogate marker lathosterol-to-cholesterol ratio in serum.

Hyperlipoproteinaemia(a) is a common cause of autosomal dominant hypercholesterolaemia.

UNLABELLED: Autosomal dominant hypercholesterolaemia (ADH) are a heterogeneous group of monogenic lipid disorders. The plasma level of lipoprotein(a) (Lp(a)) is a heritable trait associated with increased coronary heart disease (CHD) risk. OBJECTIVE: To evaluate the frequency of elevated Lp(a) as a cause of ADH and the characteristics of subjects with high Lp(a) (hyperLp(a)). MATERIAL AND METHODS: 200 healthy subjects and 933 unrelated Spanish subjects with a clinical diagnosis of ADH who were screened for low-density lipoprotein receptor (LDLR) and apolipoprotein B (APOB) gene mutations. Standard cardiovascular risk factors and blood lipid levels, including Lp(a), were evaluated. HyperLp(a) was defined as Lp(a) levels >or=95th centile of control values. RESULTS: Lp(a) was higher in 263 subjects without LDLR or APOB mutations (nonLDLR/nonAPOB group) than in 670 subjects with mutations (FH group): 40.0 mg/dl (interquartile range (IR) 15.0-89.0) versus 31.0 mg/dl (IR 11.0-73.7) respectively, p = 0.002. HyperLp(a) was present in 23% of ADH subjects (odds ratio (OR) 5.6 (95% CI, 2.9 to 10.7) versus controls) and 29% of nonLDLR/nonAPOB subjects (OR 7.7; 3.9 to 15.4). After adjusting for Lp(a), LDL cholesterol levels were <95th centile in 28 (10.6%) nonLDLR/nonAPOB subjects and in 9 (1.3%) FH subjects. Lp(a) levels were nonsignificantly higher in ADH subjects with early-onset CHD than in those without (43.5 mg/dl, (IR, 12.0-82.0) versus 31.7 mg/dl (11.8-76.5), respectively). CONCLUSIONS: HyperLp(a) is responsible for ADH in approximately 6% of nonLDLR/nonAPOB subjects. HyperLp(a) would not appear to be a risk factor for early-onset CHD in ADH, independently of whether genetic defects have or have not been demonstrated.

Apolipoprotein E genotype is not associated with cardiovascular disease in heterozygous subjects with familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is a genetic disorder characterized by high low-density lipoprotein cholesterol levels and premature cardiovascular disease (CVD). There are important differences in the presence of CVD among heterozygous subjects with FH. Some of this variability can be explained by genetic factors, and the apolipoprotein (apo) E genotype has been proposed as a useful marker. METHODS: We analyzed the apo E genotype in 706 non-related subjects who were heterozygous for FH from Spain. CVD was present in 198 subjects (28%), 132 men (41%) and 66 women (17%). RESULTS: Apo E allele frequencies for the epsilon 3, epsilon 4, and epsilon 2 alleles were 0.89, 0.09, and 0.02 respectively. Age, body mass index, smoking status, high blood pressure, diabetes mellitus, presence of tendon xanthomas, total cholesterol level, triglyceride levels, high-density lipoprotein cholesterol level, low-density lipoprotein cholesterol level, and Lp(a) did not differ among genotypes. The incidence of CVD and the age of onset of CVD did not differ among genotypes either. In the multivariant analysis, apo E genotype did not contribute significantly to CVD. CONCLUSIONS: Heterozygous men with FH have a very high risk of coronary disease in a Mediterranean country, and the apo E genotype in this large group of adults with FH is not associated either with CVD or lipid values, in contrast with the established effect in the general population.

Hematological indices as markers of ischemic heart disease in young smokers.

This paper evaluates the hematological indices in young smokers compared to non-smokers of similar age, diet, physical exercise, profession and alcohol consumption.

Changes in the atherogenic profile of patients with type 1 Gaucher disease after miglustat therapy.

OBJECTIVE: Type 1 Gaucher disease (GD1) is an autosomal recessive lysosomal storage disorder associated with abnormal accumulation of glucocerebrosides. Plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) are decreased in GD1 patients. The effects of substrate reduction therapy (SRT) with miglustat on plasma lipids and atherogenic factors have not yet been examined. Here, we report plasma atherogenic profile data from GD1 patients undergoing long-term SRT. METHODS: Plasma was analysed in 26 GD1 patients treated with miglustat for up to 36 months. Ten patients were therapy-naïve and 16 had switched from enzyme replacement therapy (ERT); the interval between stopping ERT and starting SRT was 2-6 weeks. Plasma TC, triglycerides (TG), LDL-c, HDL-c, apolipoproteins (apoA-I, apoB, and Lp[a]), C-reactive protein (CRP) concentrations, and chitotriosidase activity were measured before SRT (baseline) and at 12, 24, and 36 months follow up. RESULTS: In therapy-naïve patients, miglustat significantly increased plasma HDL-c and apoA-I, and slightly increased TC; while TG, CRP concentrations, and TC/HDL-c ratios decreased significantly after 24 months. In contrast, there were no changes in HDL-c and apoA-I, or in the TC/HDL-c ratio in switch patients. However, a decrease in CRP was observed after 12 months. LDL-c and apoB were not significantly altered in either patient group. CONCLUSIONS: Miglustat appears to have beneficial effects on plasma lipid, lipoprotein, and CRP concentrations in therapy-naïve GD1 patients, resulting in an improved atherogenic lipid profile. Further studies are required to determine the effect of miglustat on coronary heart disease risk.

Comparison of the hypolipidemic effect of gemfibrozil versus simvastatin in patients with type III hyperlipoproteinemia.

BACKGROUND: Type III hyperlipoproteinemia is characterized by the accumulation of chylomicron and very low density lipoprotein (VLDL) remnants. Individuals with this disorder have a high risk of premature atherosclerosis, and hypolipidemic drugs are useful in their management. METHODS: We compared, in a double-blind, placebo-controlled, randomized crossed study, the effects of gemfibrozil (1200 mg/day) and simvastatin (20 mg/day) on lipids, apolipoprotein AI, apolipoprotein B, and apolipoprotein E and on lipids and apolipoprotein B content in VLDL, intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) in 10 patients with type III hyperlipoproteinemia. RESULTS: Levels of total cholesterol, VLDL cholesterol, IDL cholesterol, and apolipoprotein B decreased with both drugs. Larger reductions in triglycerides (109 +/- 28.2 mg/dL, P =.005), VLDL cholesterol (24.7 +/- 10.9 mg/dL, P =.05), and VLDL triglycerides (86.3 +/- 20.2 mg/dL, P =.003) were obtained with gemfibrozil compared with simvastatin. LDL cholesterol reduction was more effective with simvastatin than with gemfibrozil (44.3 +/- 17.1 mg/dL, P =.03). HDL cholesterol after gemfibrozil was 5.71 +/- 2.37 mg/dL higher than after simvastatin. CONCLUSIONS: In patients with type III hyperlipoproteinemia gemfibrozil is more effective in reducing total triglyceride and VLDL lipid levels than simvastatin, and simvastatin is better in reducing LDL cholesterol than gemfibrozil is. IDL and apolipoprotein E levels were reduced similarly with both drugs.

Tobacco, physical exercise and lipid profile.

A group of 572 young cadets from the General Military Academy in Zaragoza (AGEMZA) with a mean age of 19.9 years was studied in two different situations: on admission to the AGEMZA, when physical activity was very intensive (A) and after 8 months, by which time they had all received identical diets and physical activity was considerably reduced (B). On both occasions they were asked about their smoking habits and their personal and family histories. Their height and weight were recorded and a sample of venous blood was taken to determine the lipid, biochemical and haematological profiles. We found that more smokers had a family history of sudden death or acute myocardial infarction than the non-smokers. The smokers also showed a lower HDL cholesterol level (54.3 +/- 9.8 mg.dl-1 +/- SD) than the non-smokers (59.4 +/- 10.9) (P less than 0.0001) and a higher level of triglycerides (75.4 +/- 24.7 mg.dl-1) than the non-smokers (65.4 +/- 21.1 mg.dl-1). The smokers had a higher white cell count (8194 +/- 1981 vs 7332 +/- 1672 cells. 10mm-3) (P less than 0.001), a higher haemoglobin value (14.9 +/- 0.9 vs 14.6 +/- 0.9 g.dl-1) (P less than 0.004) and a higher haematocrit value (44.2 +/- 2.3 vs 43.6 +/- 2.7%) (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Papel de los esteroles vegetales de la dieta sobre la absorción intestinal de colesterol y sus niveles plasmáticos / Role of naturally-occurring plant sterols on intestinal cholesterol absorption and plasmatic levels

Cardiovascular disease is a major health problem in developed countries althoughits incidence is relatively lower in Mediterranean countries which is partly ascribedto dietary habits. Epidemiologic evidence shows that elevated serum cholesterol,specifically low-density lipoprotein cholesterol (c-LDL), increases cardiovasculardisease. Phytosterols are bioactive compounds, found in all vegetable foods, whichinhibit intestinal cholesterol absorption and, therefore, have a serum cholesterolloweringeffect. Intestinal cholesterol absorption is a multistep process where plantsterols and stanols may act: a) attenuating the NPC1L1 gene expression, which mayresult in a lower cholesterol uptake from the lumen; b) lowering the cholesterol esterificationrate by the ACAT2 (acyl-CoA cholesterol acyltransferase) and, consequently,the amount of cholesterol secreted via the chylomicrons and c) upregulatingthe expression of ABC-transporters ABCG5 and ABCG8 in intestinal cells, whichmay result in an increased excretion of cholesterol by the enterocyte back into thelumen. Many clinical trials proved that commercial products enriched with phytosterolsreduce cholesterol levels. Likewise, recent studies show that phytosterols presentin natural food matrices are also effective and could be an important componentof cardioprotective dietary patterns such as the Mediterranean diet(AU)

La enfermedad cardiovascular es un problemade salud importante en los países desarrollados,aunque su incidencia es relativamentemenor en los países mediterráneos lo que esparcialmente atribuible a los hábitos dietéticos.Existen evidencias epidemiológicas que muestranque el colesterol sérico elevado, específicamenteel colesterol ligado a las lipoproteínas debaja densidad (c-LDL), incrementa la enfermedadcardiovascular. Los fitosteroles son compuestosbioactivos, presentes en todos los alimentosde origen vegetal, que inhiben la absorciónintestinal de colesterol y, por lo tanto, tienenun efecto reductor en el colesterol sérico.La absorción intestinal de colesterol es un procesomulti-etapa donde los esteroles y estanolesvegetales pueden actuar de diversas formas:a) atenuando la expresión del gen NPC1L1, loque puede suponer una disminución del ingresode colesterol desde el lumen intestinal; b)disminuyendo la tasa de esterificación delcolesterol por la ACAT2 (acil-CoA colesterolaciltransferasa) y, en consecuencia, la cantidadde colesterol excretada vía quilomicrones y c)aumentando la expresión de los ABC-transportadoresABCG5 y ABCG8 en las célulasintestinales, lo que puede derivar en una excreción incrementada de colesterol desde el enterocitohacia el lumen. Diversos ensayos clínicoshan demostrado que los productos comercialesenriquecidos con fitosteroles reducen losniveles de colesterol. Sin embargo, estudiosrecientes muestran que los fitosteroles presentesen matrices alimentarias naturales tambiénpueden ser bioactivos y podrían ser un componenteimportante de los patrones dietéticoscardioprotectores como es la dieta Mediterránea(AU)

A moderate intake of phytosterols from habitual diet affects cholesterol metabolism

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Cholesterol metabolism homeostasis is the result of a balance between synthesis, degradation and intestinal absorption. It is well established that intestinal cholesterol absorption efficiency can be modified by the intake of phytosterol-enriched food and, therefore, have a serum cholesterol-lowering effect. Recent epidemiological and clinical studies have shown that presence of phytosterols at normal diet levels could also be effective on lowering total and LDL serum cholesterol since they affect whole-body cholesterol metabolism even at those moderate doses. The aim of this study was to analyze the effect of the levels of the naturally-occurring phytosterols in the diet on cholesterol metabolism parameters. In order to do that a group of 99 healthy volunteers was studied for their dietary habits and surrogate markers of cholesterol synthesis and absorption. The mean daily dietary intake of phytosterols, measured by a food semiquantitative frequency questionnaire, was found to be 494 mg being beta-sitosterol the major contributor to it. Subjects were classified into tertiles according to their total phytosterol intake and comparisons were done between subgroups. No statistical differences were observed for surrogate markers of intestinal cholesterol absorption, but a significant increase in the cholesterol synthesis surrogate marker lathosterol-to-cholesterol ratio associated to highest dietary phytosterol intake was observed. Regardless of this, only a non significant trend toward a less atherogenic lipid profile was observed in the upper tertile. In conclusion, the intake of moderate amounts of phytosterols naturally present in habitual diet may affect cholesterol metabolism and specially the rate of cholesterol synthesis as estimated by the surrogate marker lathosterol-to-cholesterol ratio in serum (AU)