Clinical characteristics of premature cardiovascular disease in our health area.

INTRODUCTION AND OBJECTIVES: Cardiovascular disease continues to be the main cause of mortality, but few data are available in the young population. The aim of our study was to know the incidence and clinical characteristics of premature cardiovascular disease in our health area. METHODS: Cross-sectional study of patients admitted for acute episode of premature cardiovascular disease in a referral hospital during 2018. RESULTS: We detected 367 subjects: 306 (83.4%) with atherosclerotic cardiovascular disease. Almost half (164, 44.7%) were diabetic, with primary hypercholesterolaemia or high cardiovascular risk, and 84 (22.9%) had a personal history of cardiovascular disease. Among those with elevated risk or history (n = 207) only 47 subjects had LDL cholesterol at therapeutic target. CONCLUSIONS: Most of the subjects with premature cardiovascular disease in our study had higher cardiovascular risk than attributable to their age. Intensive diagnosis and treatment of cardiovascular risk factors may prevent cardiovascular disease in young adults.

High-quality intake of carbohydrates is associated with lower prevalence of subclinical atherosclerosis in femoral arteries: The AWHS study.

BACKGROUND AND AIMS: High-quality of the carbohydrates consumed, apart from their total amount, appear to protect from cardiovascular disease (CVD). However, the relationship between the quality of carbohydrates and the early appearance of atherosclerosis has not yet been described. Our objective was to estimate the association between the quality of dietary carbohydrates and subclinical atherosclerosis in femoral and carotid arteries. METHODS: Cross-sectional study of femoral and carotid atherosclerosis assessed using ultrasounds of 2074 middle-aged males, 50.9 (SD 3.9) years old, with no previous CVD, and pertaining to the Aragon Workers' Health Study (AWHS) cohort. Food frequency questionnaires were used to calculate a carbohydrate quality index (CQI) defined as: consumption of dietary fiber, a lower glycemic index, the ratio of whole grains/total grains, and the ratio of solid carbohydrates/total carbohydrates. The presence of plaques across four CQI intervals was studied using adjusted logistic regression models. RESULTS: The CQI showed a direct inverse association with subclinical atherosclerosis in femoral territories. Participants with a higher consumption of high-quality carbohydrates (13-15 points) were less likely to have femoral plaques when compared with participants in the lowest index interval (4-6 points) (OR = 0.59; 95% CI = 0.39, 0.89; p = 0.005). No association was found between the CQI and the presence of subclinical atherosclerosis in carotid territories. A lower consumption of high-quality carbohydrates tended to be associated with a greater atherosclerosis extension, considered as the odds for having more affected territories (p = 0.011). CONCLUSIONS: Among middle-aged males, a high-quality intake of carbohydrates is associated with a lower prevalence of femoral artery subclinical atherosclerosis when compared with a lower consumption. Thus, indicating an early relationship between the quality of carbohydrates and the development of CVD.

ANGPTL3 gene variants in subjects with familial combined hyperlipidemia.

Angiopoietin-like 3 (ANGPTL3) plays an important role in lipid metabolism in humans. Loss-of-function variants in ANGPTL3 cause a monogenic disease named familial combined hypolipidemia. However, the potential contribution of ANGPTL3 gene in subjects with familial combined hyperlipidemia (FCHL) has not been studied. For that reason, the aim of this work was to investigate the potential contribution of ANGPTL3 in the aetiology of FCHL by identifying gain-of-function (GOF) genetic variants in the ANGPTL3 gene in FCHL subjects. ANGPTL3 gene was sequenced in 162 unrelated subjects with severe FCHL and 165 normolipemic controls. Pathogenicity of genetic variants was predicted with PredictSNP2 and FruitFly. Frequency of identified variants in FCHL was compared with that of normolipemic controls and that described in the 1000 Genomes Project. No GOF mutations in ANGPTL3 were present in subjects with FCHL. Four variants were identified in FCHL subjects, showing a different frequency from that observed in normolipemic controls: c.607-109T>C, c.607-47_607-46delGT, c.835+41C>A and c.*52_*60del. This last variant, c.*52_*60del, is a microRNA associated sequence in the 3'UTR of ANGPTL3, and it was present 2.7 times more frequently in normolipemic controls than in FCHL subjects. Our research shows that no GOF mutations in ANGPTL3 were found in a large group of unrelated subjects with FCHL.

Carotid atherosclerosis and lipoprotein particle subclasses in familial hypercholesterolaemia and familial combined hyperlipidaemia.

BACKGROUND AND AIMS: Familial hypercholesterolaemia (FH) and familial combined hyperlipidaemia (FCH) are common atherogenic disorders with great variability in cardiovascular disease (CVD). No direct atherosclerosis burden comparisons have been performed between FH and FCH in relation to lipoprotein particle distribution. METHODS AND RESULTS: Risk factors and three measures of carotid intima-media thickness (IMT) in both sides were determined in 572 FH, 250 FCH and 200 controls. Lipoproteins were assessed by nuclear magnetic resonance (NMR) spectroscopy. Compared with controls, IMT measures were increased in FH and FCH. FCH had the highest adjusted mean-maximum IMT. FH had twice low-density lipoprotein (LDL) particles than controls, but similar LDL subclass size and distribution. FCH subjects also had increased LDL particles and the highest number of small LDL (1519 ± 731 nmol l(-1) vs. 887 ± 784 nmol l(-1) in FH and 545 ± 409 nmol l(-1) in controls). Age, gender, cholesterol/high-density lipoprotein (HDL) ratio, smoking and systolic blood pressure were independently associated with IMT in FH (r(2) = 0.38). The same variables, except cholesterol/HDL ratio, were associated with IMT in FCH (r(2) = 0.40). Among NMR lipoproteins, only VLDL and chylomicrons increased IMT prediction in FCH by 0.8%. CONCLUSION: FH and FCH subjects show increased carotid atherosclerosis in relation to classical risk factors. Lipoprotein subclasses do not substantially contribute to IMT variability.

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.

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.

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.