Juan Pedro-Botet

Apolipoprotein E genotype and cardiovascular disease in the Framingham Heart Study

BACKGROUNDnApolipoprotein (apo) E is a constituent of lipoproteins with considerable variation due to cysteine-arginine exchanges. The apo E4 (Arg112-Cys) polymorphism has been associated with dementia and hypercholesterolemia. We investigated the relation of APOE genotype to cardiovascular disease (CVD) in the Framingham Offspring Study.nnnMETHODS AND RESULTSnDNA was isolated from 3413 study participants and APOE genotypes were determined utilizing the polymerase chain reaction and restriction isotyping. In the entire group of subjects, 20.7% had apo E4/4 or E3/4 (Group E4); 14.1% had apo E2/2 or E2/3 (Group E2) and 63.9% had the apo E3/3 genotype (Group E3). Subjects with E2/4 (1.3%) were excluded. Period prevalence of CVD between examinations 1 and 5 (1971-1994) (366 events) was related to APOE genotype. Age adjusted period prevalence of CVD in men was 18.6% for Group E4, 18.2% for Group E2 and 12.7% for Group E3 (P=0.004); while in women these rates were 9.9, 4.9, and 6.6%, respectively (P=0.037). After adjustment for non-lipid risk factors the relative odds for CVD in Group E2 men was 1.79 (P=0.0098) and in Group E4 it was 1.63 (P=0.0086) compared with the Group E3; while in Group E4 women it was 1.56 (P=0.054). After adjustment for all CVD risk factors, the relative odds in Group E2 men was 1.94 (P=0.004) and in Group E4 men it was 1.51 (P=0.0262).nnnCONCLUSIONSnThe presence of the apo E2 or apo E4 alleles in men is associated with significantly greater CVD risk. This genotypic information may help to identify individuals at increased risk for CVD events.

Apolipoprotein E genotype affects plasma lipid response to atorvastatin in a gender specific manner

The response to therapy with hypolipidemic agents shows considerable individual variation. These differences may be due to the interaction of environmental and genetic factors that affect drug bioavailability, receptor function or ligand structure. Our objective was to assess the effect of apolipoprotein (apo) E genotype and gender on lipid-lowering response to the HMG CoA reductase inhibitor, atorvastatin. Genotyping was carried out on DNA from 328 male and female subjects who participated in a multicentric, double-blind clinical trial, and received 10 mg/day of atorvastatin. Our data demonstrate no significant gender differences for LDL cholesterol levels at baseline. Moreover, mean LDL-C lowering was similar in men (-36.2%, range -2.7 to -57.8%) and in women (-38.1%, range -9.5 to -58.5%) as compared to baseline. However, men carrying the epsilon2 allele had a significantly higher mean LDL-C response (-44%) than epsilon3 homozygotes (-37%) and epsilon4 carriers (-34%); P=0.01 for apoE group by treatment interaction. No such gene/treatment interactions were noted in women, with those carrying the epsilon2 allele showing a similar mean response (-34%) as epsilon3 homozygotes (-39%) and epsilon4 carriers (-34%). Mean plasma triglyceride lowering with atorvastatin was 17%. A significant apoE group by treatment interaction (P=0.010) was also observed in men, with epsilon2 carriers being more responsive (-27%) than epsilon3/3 (-13%) and epsilon4 (-22%). This interaction was not observed in women. In summary, atorvastatin treatment had similar effects on plasma lipid levels in both men and women; however, the apoE gene locus was a significant predictor of LDL-C and TG responses to atorvastatin therapy in men, but not in women.

Apoprotein E genotype and the response of serum cholesterol to dietary fat, cholesterol and cafestol

Previous studies on the effect of apoprotein E (APOE) polymorphism on the response of serum lipids to diet showed inconsistent results. We therefore studied the effect of apoprotein E polymorphism on responses of serum cholesterol and lipoproteins to various dietary treatments. We combined data on responses of serum cholesterol and lipoproteins to saturated fat, to trans-fat, to dietary cholesterol, and to the coffee diterpene cafestol with newly obtained data on the apoprotein E polymorphism in 395 mostly normolipidemic subjects. The responses of low-density lipoprotein (LDL-) cholesterol to saturated fat were 0.08 mmol/l larger in subjects with the APOE3/4 or E4/4 genotype than in those with the APOE3/3 genotype (95% confidence interval: -0.01-0.18 mmol/l). In contrast, responses of LDL-cholesterol to cafestol were 0.11 mmol/l smaller in subjects with the APOE3/4 or E4/4 genotype than in those with the APOE3/3 genotype (95% confidence interval: -0.29-0.07 mmol/l). Responses to dietary cholesterol and trans-fat did not differ between subjects with the various APOE genotypes. In conclusion, the APOE genotype may affect the response of serum cholesterol to dietary saturated fat and cafestol in opposite directions. However, the effects are small. Therefore, knowledge of the APOE genotype by itself may be of little use in the identification of subjects who respond to diet.

The apolipoprotein E4 allele is not associated with an abnormal lipid profile in a Native American population following its traditional lifestyle

The apolipoprotein E4 allele is associated in industrialized countries with an elevated LDL cholesterol concentration and an increased cardiovascular risk. Our purpose in this study was to assess the influence of the genetic variation at the APOE gene locus on the lipid profile of a Native American rural population. We examined plasma lipid levels and the common apo E alleles in 142 healthy randomly selected adults living in their native communities in western Mexico. Their age was 38+/-17 years and the BMI 25.7+/-4.5 kg/m2. Plasma cholesterol, triglycerides, LDL C and HDL C were 165+/-29.6, 126+/-83, 98+/-26 and 42+/-12.7 mg/dl respectively. Ninety-one per cent of the subjects had Lp(a) concentrations below 20 mg/dl and 30% had levels lower than 2 mg/dl. The most common APOE genotype was E3/3 (63%), followed by E3/4 (30.1%). The prevalence of the E2 allele was very low (2.3%). No difference was observed in LDL C concentrations between the E3/E3 and E3/E4 subjects; however carriers of the E2/3 genotype had lower LDL C levels. Similar results were obtained for cholesterol and apo B levels. In summary, the increased LDL C levels associated with the E4 allele in previous studies were not observed in a population with non-westernized habits. Environmental factors, such as diet and lifestyle, could outweigh the hypercholesterolemic predisposition resulting from the presence of the apo E4 allele.

Laparoscopic sleeve gastrectomy: More than a restrictive bariatric surgery procedure?

Sleeve gastrectomy (SG) is a restrictive bariatric surgery technique that was first used as part of restrictive horizontal gastrectomy in the original Scopinaro type biliopancreatic diversion. Its good results as a single technique have led to a rise in its use, and it is currently the second most performed technique worldwide. SG achieves clearly better results than other restrictive techniques and is comparable in some aspects to the Roux-en-Y gastric bypass, the current gold standard in bariatric surgery. These benefits have been associated with different pathophysiologic mechanisms unrelated to weight loss such as increased gastric emptying and intestinal transit, and activation of hormonal mechanisms such as increased GLP-1 hormone and decreased ghrelin. The aim of this review was to highlight the salient aspects of SG regarding its historical evolution, pathophysiologic mechanisms, main results, clinical applications and perioperative complications.

Significance of High Density Lipoprotein-Cholesterol in Cardiovascular Risk Prevention

In the approach to lipid-related risk factors for cardiovascular diseases, serum high density lipoprotein-cholesterol (HDL-C) levels bear a particular significance as this lipoprotein is considered to be an antiatherogenic factor mainly, but not only, because of its influence and impact on reverse cholesterol transport. Hence the need and requirement to consider serum HDL-C levels for both primary and secondary prevention of cardiovascular disease. A particularly important aspect is the association of the ‘low HDL syndrome’ with the metabolic syndrome.These factors force us to consider serum HDL-C level as a therapeutic target by itself, or even in association with low density lipoprotein-cholesterol (LDL-C) levels when the latter are increased. This review stresses the aspects connecting serum HDL-C levels and cardiovascular risk, and looks at the populations that should be considered amenable to therapeutic management because of low serum HDL-C levels.We review therapeutic strategies, both pharmacological and nonpharmacological. The aim of this review is to present therapeutic management recommendations for correcting the proportion of cardiovascular risk that is attributable to changes in HDL-C. Serum HDL-C levels of >40 mg/dL must be a therapeutic target in primary and secondary prevention. This goal is particularly important in patients with low serum HDL-C levels and ischemic heart disease (IHD) or its equivalents, even if the therapeutic target for serum LDL-C levels (<100 mg/ dL) has been achieved. The first choice for this clinical condition is fibric acid derivates. The same therapeutic option should be considered in patients without IHD with low serum HDL-C levels and high cardiovascular risk (>20%), hypertriglyceridemia, type 2 diabetes mellitus, or metabolic syndrome.

Statins for primary cardiovascular prevention in the elderly

The elderly population is increasing worldwide, with subjects > 65 years of age constituting the fastest-growing age group. Furthermore, the elderly face the greatest risk and burden of cardiovascular disease mortality and morbidity. Although elderly patients, particularly those older > 75, have not been well represented in randomized clinical trials evaluating lipid-lowering therapy, the available evidence supporting the use of statin therapy in primary prevention in older individuals is derived mainly from subgroup analyses and post-hoc data. On the other hand, elderly patients often have multiple co-morbidities that require a high number of concurrent medications; this may increase the risk for drug-drug interactions, thereby reducing the potential benefits of statin therapy. The aim of this review was to present the relevant literature regarding statin use in the elderly for their primary cardiovascular disease, with the associated risks and benefits of treatment.

Consenso de expertos sobre la detección y el manejo clínico de la hipercolesterolemia familiar

Familial hypercholesterolemia (FH) is one of the most common and severe genetic diseases, causing disabilities and premature death to those who suffer it. Lipid-lowering therapy substantially improves the prognosis of FH patients and, therefore, appropriate pharmacological treatment is of the utmost importance. The Spanish Society of Arteriosclerosis (SEA) has always been a pioneer in the diagnosis and treatment of FH. Since its inception, FH has been one of the main areas of clinical and scientific interest, mainly for Lipids Units of the SEA, where most patients with this pathology are referred in Spain. This document arises from the willingness of our society to update the scientific knowledge on this subject and to provide physicians with clear clinical guidelines regarding diagnosis and treatment of FH. These guidelines can be summarized in two main aspects: early diagnosis of the disease and a rapid normalization of LDLcholesterol. In the coming years, health providers should accomplish that the majority of patients with FH are aware of their diagnosis and that adequate treatment is provided.

Prevalencia del síndrome metabólico y de sus componentes en pacientes con síndrome coronario agudo

INTRODUCTION AND OBJECTIVESnA large proportion of patients with coronary disease have metabolic syndrome, although the frequency and association of its different components are not well understood. The aim of this study was to determine the prevalence of metabolic syndrome and the combination of its components in a Spanish cohort of patients with acute coronary syndrome.nnnMETHODSnClinical histories of 574 inpatients with acute coronary syndrome in 6 tertiary hospitals were reviewed and the presence of metabolic syndrome and its components determined by applying Adult Treatment Panel III criteria. In a second step, the components of the metabolic syndrome were analyzed, excluding those patients with diabetes mellitus.nnnRESULTSnThe metabolic syndrome was present in 50.9% of patients and was more frequent in women than in men (66.3% vs. 47.3%; P<.001). The most prevalent component was carbohydrate metabolism disorder (85.3%), followed by low high-density lipoprotein cholesterol (HDLc) levels (80.5%). In nondiabetic patients, 34.6% had metabolic syndrome and the most prevalent component was low HDLc levels (86%), followed by high blood pressure and hypertriglyceridemia and, in fourth place, impaired fasting serum glucose levels.nnnCONCLUSIONSnThe metabolic syndrome has a high prevalence in patients with an acute coronary syndrome, especially in women. The most frequent components are hyperglycemia and low HDLc levels. After excluding diabetic patients, the most prevalent diagnostic criterion of metabolic syndrome was low HDLc levels. Full English text available from: www.revespcardiol.org.

Effect of a high saturated fat and cholesterol diet supplemented with squalene or β-sitosterol on lipoprotein profile in fib hamsters

The effects of a high saturated fat and cholesterol diet, supplemented with squalene or β-sitosterol, on plasma lipoprotein levels in animals were evaluated. Thirty-six male adult F1B hamsters were fed for four weeks on a diet rich in saturated fatty acids composed of 90% chow diet, 10% coconut oil and 0.05% cholesterol. Subsequently, the animals were randomly assigned to three different diet groups (12 animals per group) for four weeks. Group 1 animals consumed the same high-fat diet; group 2 the high-fat diet supplemented with 1% squalene, and group 3 the high-fat diet supplemented with 0.5% β-sitosterol. Results show that squalene does not modify plasma lipoprotein levels. However, in animals that consumed the diet high in saturated fat and cholesterol supplemented with β-sitosterol, plasma levels of total cholesterol, triglycerides and the total cholesterol/HDL-cholesterol ratio decreased by 33%, 49% and 48%, respectively. This reduction in total cholesterol was probably associated with decreased absorption of cholesterol and lower incorporation in chylomicrons and VLDL + IDL. However, cholesterol absorption per se was not measured in this experiment. Plasma triglyceride levels decreased in all lipoprotein fractions. In conclusion, under our experimental conditions, β-sitosterol exerts a hypocholesterolemic and hypotriglyceridemic effect in experimental animals. However, the addition of squalene (1%) to this diet produces no effect on plasma lipoprotein levels.