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Reducing dietary saturated fatty acids (SFA) intake results in a clinically significant lowering of low-density lipoprotein cholesterol (LDL-C) across ethnicities. In contrast, dietary SFA's role in modulating emerging cardiovascular risk factors in different ethnicities remains poorly understood. Elevated levels of lipoprotein(a) [Lp(a)], an independent cardiovascular risk factor, disproportionally affect individuals of African descent. Here, we assessed the responses in Lp(a) levels to dietary SFA reduction in 166 African Americans enrolled in GET-READI (The Gene-Environment Trial on Response in African Americans to Dietary Intervention), a randomized controlled feeding trial. Participants were fed two diets in random order for 5 weeks each: 1) an average American diet (AAD) (37% total fat: 16% SFA), and 2) a diet similar to the Dietary Approaches to Stop Hypertension (DASH) diet (25% total fat: 6% SFA). The participants' mean age was 35 years, 70% were women, the mean BMI was 28 kg/m2, and the mean LDL-C was 116 mg/dl. Compared to the AAD diet, LDL-C was reduced by the DASH-type diet (mean change: -12 mg/dl) as were total cholesterol (-16 mg/dl), HDL-C (-5 mg/dl), apoA-1 (-9 mg/dl) and apoB-100 (-5 mg/dl) (all P < 0.0001). In contrast, Lp(a) levels increased following the DASH-type diet compared with AAD (median: 58 vs. 44 mg/dl, P < 0.0001). In conclusion, in a large cohort of African Americans, reductions in SFA intake significantly increased Lp(a) levels while reducing LDL-C. Future studies are warranted to elucidate the mechanism(s) underlying the SFA reduction-induced increase in Lp(a) levels and its role in cardiovascular risk across populations.

High levels of lipoprotein(a) [Lp(a)], an apoB100-containing lipoprotein, are an independent and causal risk factor for atherosclerotic cardiovascular diseases through mechanisms associated with increased atherogenesis, inflammation, and thrombosis. Lp(a) is predominantly a monogenic cardiovascular risk determinant, with ≈70% to ≥90% of interindividual heterogeneity in levels being genetically determined. The 2 major protein components of Lp(a) particles are apoB100 and apolipoprotein(a). Lp(a) remains a risk factor for cardiovascular disease development even in the setting of effective reduction of plasma low-density lipoprotein cholesterol and apoB100. Despite its demonstrated contribution to atherosclerotic cardiovascular disease burden, we presently lack standardization and harmonization of assays, universal guidelines for diagnosing and providing risk assessment, and targeted treatments to lower Lp(a). There is a clinical need to understand the genetic and biological basis for variation in Lp(a) levels and its relationship to disease in different ancestry groups. This scientific statement capitalizes on the expertise of a diverse basic science and clinical workgroup to highlight the history, biology, pathophysiology, and emerging clinical evidence in the Lp(a) field. Herein, we address key knowledge gaps and future directions required to mitigate the atherosclerotic cardiovascular disease risk attributable to elevated Lp(a) levels.

Lipoprotein(a) [Lp(a)] is an independent, causal, genetically determined risk factor for cardiovascular disease (CVD). We provide an overview of current knowledge on Lp(a) and CVD risk, and the effect of pharmacological agents on Lp(a). Since evidence is accumulating that diet modulates Lp(a), the focus of this paper is on the effect of dietary intervention on Lp(a). We identified seven trials with 15 comparisons of the effect of saturated fat (SFA) replacement on Lp(a). While replacement of SFA with carbohydrate, monounsaturated fat (MUFA), or polyunsaturated fat (PUFA) consistently lowered low-density lipoprotein cholesterol (LDL-C), heterogeneity in the Lp(a) response was observed. In two trials, Lp(a) increased with carbohydrate replacement; one trial showed no effect and another showed Lp(a) lowering. MUFA replacement increased Lp(a) in three trials; three trials showed no effect and one showed lowering. PUFA or PUFA + MUFA inconsistently affected Lp(a) in four trials. Seven trials of diets with differing macronutrient compositions showed similar divergence in the effect on LDL-C and Lp(a). The identified clinical trials show diet modestly affects Lp(a) and often in the opposing direction to LDL-C. Further research is needed to understand how diet affects Lp(a) and its properties, and the lack of concordance between diet-induced LDL-C and Lp(a) changes.

ApoCIII and triglyceride (TG)-rich lipoproteins (TRL), particularly, large TG-rich lipoproteins particles, have been described as important mediators of cardiovascular disease (CVD) risk. The effects of sustained consumption of dietary fructose compared with those of sustained glucose consumption on circulating apoCIII and large TRL particles have not been reported. We measured apoCIII concentrations and the TG and cholesterol content of lipoprotein subfractions separated by size in fasting and postprandial plasma collected from men and women (age: 54 ± 8 years) before and after they consumed glucose- or fructose-sweetened beverages for 10 weeks. The subjects consuming fructose exhibited higher fasting and postprandial plasma apoCIII concentrations than the subjects consuming glucose (p < 0.05 for both). They also had higher concentrations of postprandial TG in all TRL subfractions (p < 0.05, effect of sugar), with the highest increases occurring in the largest TRL particles (p < 0.0001 for fructose linear trend). Compared to glucose consumption, fructose consumption increased postprandial TG in low-density lipoprotein (LDL) particles (p < 0.05, effect of sugar), especially in the smaller particles (p < 0.0001 for fructose linear trend). The increases of both postprandial apoCIII and TG in large TRL subfractions were associated with fructose-induced increases of fasting cholesterol in the smaller LDL particles. In conclusion, 10 weeks of fructose consumption increased the circulating apoCIII and postprandial concentrations of large TRL particles compared with glucose consumption.

We previously demonstrated an association between lipoprotein (a) [Lp(a)] levels and atherosclerosis in human immunodeficiency virus (HIV)-seropositive women. The effects of antiretroviral therapy (ART) on Lp(a) levels in relation to apo(a) size polymorphism remain unclear. ART effects on allele-specific apo(a) level (ASL), an Lp(a) level associated with individual apo(a) alleles within each allele-pair, were determined in 126 HIV-seropositive women. ART effects were tested by a mixed-effects model across pre-ART and post-ART first and third visits. Data from 120 HIV-seronegative women were used. The mean age was 38 years; most were African-American (∼70%). Pre-ART ASLs associated with the larger (4.6 mg/dl vs. 8.0 mg/dl, P = 0.024) or smaller (13 mg/dl vs. 19 mg/dl, P = 0.041) apo(a) sizes were lower in the HIV-seropositive versus HIV-seronegative group, as was the prevalence of a high Lp(a) level (P = 0.013). Post-ART ASL and prevalence of high Lp(a) or apo(a) sizes and frequency of small size apo(a) (22 kringles) did not differ between the two groups. ART increased Lp(a) level (from 18 to 24 mg/dl, P < 0.0001) and both ASLs (P < 0.001). In conclusion, regardless of genetic control, Lp(a) can be modulated by HIV and its treatment. ART initiation abrogates HIV-induced suppression of Lp(a) levels and ASLs, contributing to promote CVD risk in HIV-seropositive individuals.

An elevated level of lipoprotein (a) [Lp(a)] is a risk factor for CVD. Alirocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9, is reported to reduce Lp(a) levels. The relationship of Lp(a) reduction with apo(a) size polymorphism, phenotype, and dominance pattern and LDL cholesterol (LDL-C) reduction was evaluated in a pooled analysis of 155 hypercholesterolemic patients (75 with heterozygous familial hypercholesterolemia) from two clinical trials. Alirocumab significantly reduced total Lp(a) (pooled median: -21%, P = 0.0001) and allele-specific apo(a), an Lp(a) level carried by the smaller (median: -18%, P = 0.002) or the larger (median: -37%, P = 0.0005) apo(a) isoform, at week 8 versus baseline. The percent reduction in Lp(a) level with alirocumab was similar across apo(a) phenotypes (single vs. double bands) and carriers and noncarriers of a small size apo(a) (≤22 kringles). The percent reduction in LDL-C correlated significantly with the percent reduction in Lp(a) level (r = 0.407, P < 0.0001) and allele-specific apo(a) level associated with the smaller (r = 0.390, P < 0.0001) or larger (r = 0.270, P = 0.0183) apo(a) sizes. In conclusion, alirocumab-induced Lp(a) reduction was independent of apo(a) phenotypes and the presence or absence of a small size apo(a).

ObjectiveIn the general population, lipoprotein(a) [Lp(a)] has been established as an independent causal risk factor for cardiovascular disease. Lp(a) levels are to a major extent regulated by a size polymorphism in the apolipoprotein(a) [apo(a)] gene. The roles of Lp(a)/apo(a) in human immunodeficiency virus (HIV)-related elevated cardiovascular disease risk remain unclear.Approach and resultsThe associations between total plasma Lp(a) level, allele-specific apo(a) level, an Lp(a) level carried by individual apo(a) alleles, and common carotid artery intima-media thickness were assessed in 150 HIV-infected and 100 HIV-uninfected women in the WIHS (Women's Interagency HIV Study). Linear regression analyses with and without adjustments were used. The cohort was young (mean age, ≈31 years), with the majority being Blacks (≈70%). The prevalence of a small size apo(a) (≤22 Kringle repeats) or a high Lp(a) level (≥30 mg/dL) was similar by HIV status. Total plasma Lp(a) level (P=0.029) and allele-specific apo(a) level carried by the smaller apo(a) sizes (P=0.022) were significantly associated with carotid artery intima-media thickness in the HIV-infected women only. After accounting for confounders (age, race, smoking, body mass index, blood pressure, hepatitis C virus coinfection, menopause, plasma lipids, treatment status, CD4+ T cell count, and HIV/RNA viral load), the association remained significant for both Lp(a) (P=0.035) and allele-specific apo(a) level carried by the smaller apo(a) sizes (P=0.010) in the HIV-infected women. Notably, none of the other lipids/lipoproteins was associated with carotid artery intima-media thickness.ConclusionsLp(a) and allele-specific apo(a) levels predict carotid artery intima-media thickness in HIV-infected young women. Further research is needed to identify underlying mechanisms of an increased Lp(a) atherogenicity in HIV infection.

Levels of lipoprotein (a) [Lp(a)], a complex between an LDL-like lipid moiety containing one copy of apoB, and apo(a), a plasminogen-derived carbohydrate-rich hydrophilic protein, are primarily genetically regulated. Although stable intra-individually, Lp(a) levels have a skewed distribution inter-individually and are strongly impacted by a size polymorphism of the LPA gene, resulting in a variable number of kringle IV (KIV) units, a key motif of apo(a). The variation in KIV units is a strong predictor of plasma Lp(a) levels resulting in stable plasma levels across the lifespan. Studies have demonstrated pronounced differences across ethnicities with regard to Lp(a) levels and some of this difference, but not all of it, can be explained by genetic variations across ethnic groups. Increasing evidence suggests that age, sex, and hormonal impact may have a modest modulatory influence on Lp(a) levels. Among clinical conditions, Lp(a) levels are reported to be affected by kidney and liver diseases.

ObjectivesLipoprotein(a) [Lp(a)] is mainly similar in composition to LDL, but differs in having apolipoprotein (apo) (a) covalently linked to apoB-100. Our purpose was to examine the individual metabolism of apo(a) and apoB-100 within plasma Lp(a).Materials and methodsThe kinetics of apo(a) and apoB-100 in plasma Lp(a) were assessed in four men with dyslipidemia [Lp(a) concentration: 8.9-124.7nmol/L]. All subjects received a primed constant infusion of [5,5,5-(2)H3] L-leucine while in the constantly fed state. Lp(a) was immunoprecipitated directly from whole plasma; apo(a) and apoB-100 were separated by gel electrophoresis; and isotopic enrichment was determined by gas chromatography/mass spectrometry.ResultsMulticompartmental modeling analysis indicated that the median fractional catabolic rates of apo(a) and apoB-100 within Lp(a) were significantly different at 0.104 and 0.263 pools/day, respectively (P=0.04). The median Lp(a) apo(a) production rate at 0.248nmol/kg·day(-1) was significantly lower than that of Lp(a) apoB-100 at 0.514nmol/kg·day(-1) (P=0.03).ConclusionOur data indicate that apo(a) has a plasma residence time (11days) that is more than twice as long as that of apoB-100 (4days) within Lp(a), supporting the concept that apo(a) and apoB-100 within plasma Lp(a) are not catabolized from the bloodstream as a unit in humans in the fed state.

ObjectiveLevels of lipoprotein(a), Lp(a), an independent risk factor for cardiovascular disease (CVD), are affected by sex hormones. Women with polycystic ovary syndrome (PCOS) have elevated androgen levels and are at increased CVD risk. We investigated the impact of PCOS-related hormonal imbalance on Lp(a) levels in relation to apo(a) gene size polymorphism, a major regulator of Lp(a) level.DesignCross-sectional.PatientsForty-one Caucasian women with PCOS based on the NIH criteria.Measurements(1) Apo(a) gene size polymorphism measured as Kringle (K) 4 repeat number; (2) total plasma Lp(a) level; (3) allele-specific apo(a) level assessing the amount of Lp(a) carried by an individual apo(a) allele/isoform; and (4) sex hormone levels.ResultsThe mean age was 32 ± 6 years, and the mean BMI was 35 ± 8 with 66% of women classified as obese (BMI >30 kg/m2 ). LDL cholesterol was borderline high (3·37 mmol/l), and HDL cholesterol was low (1·06 mmol/l). The distribution of Lp(a) level was skewed towards lower levels with a median level of 22·1 nmol/l (IQR: 6·2-66·5 nmol/l). Lp(a) levels were not correlated with age, body weight or BMI. The median allele-specific apo(a) level was 10·6 nmol/l (IQR: 3·1-31·2 nmol/l), and the median apo(a) size was 27 (IQR: 23-30) K4 repeats. Allele-specific apo(a) levels were significantly and inversely correlated with K4 repeats (r = -0·298, P = 0·007). Neither Lp(a) nor allele-specific apo(a) levels were significantly associated with testosterone or dehydroepiandrosterone sulphate levels.ConclusionsThe apo(a) genetic variability remains the major regulator of plasma Lp(a) levels in women with PCOS.

BackgroundLevels of lipoprotein(a), Lp(a), a genetically regulated independent cardiovascular risk factor present in humans and Old World monkeys, are impacted by the apolipoprotein(a), apo(a), gene. Allele-specific apo(a) levels, taking both the apo(a) genotypic and phenotypic characteristics into account, are useful markers to determine atherosclerotic cardiovascular risk.MethodsWe determined (i) the genetic variability of apo(a), (ii) Lp(a) levels, and (iii) allele-specific apo(a) levels in rhesus monkeys (n = 95).ResultsLp(a) levels differed substantially between animals (range: 4-247 nmol/l) with a skewed distribution toward lower levels. Lp(a) and allele-specific apo(a) levels were inversely related to the number of apo(a) Kringle 4 (K4) repeats. The median apo(a) size was 23 K4 repeats, and the prevalence of a small size apo(a) (≤22 K4) was 43%.ConclusionsDistribution of Lp(a) and allele-specific apo(a) levels in rhesus monkeys reflected the corresponding human patterns, but with a high prevalence of smaller apo(a) sizes.

ObjectivesLipoprotein(a), Lp(a), represents an apolipoprotein (apo) B-carrying lipoprotein, yet the relationship between Lp(a) and apoB levels has not been fully explored.MethodsWe addressed the relationship between Lp(a) and apoB-containing lipoprotein levels in 336 Caucasians and 224 African-Americans. Our approach takes unique molecular properties of Lp(a) as well as contribution of Lp(a) to the levels of these lipoproteins into account.ResultsLevels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apoB and apoB/apoA-1 did not differ across ethnicity. African-Americans had higher levels of Lp(a) and high-density lipoprotein cholesterol and lower triglyceride levels compared to Caucasians. Lp(a) levels were correlated with levels of TC (p < 0.005), LDL-C (p < 0.001), apoB (p < 0.05) or apoB/apoA-1 (p < 0.05) in both ethnic groups. These associations remained significant only in African-Americans after adjustments for the contribution of Lp(a)-cholesterol or Lp(a)-apoB. Furthermore, taking Lp(a)-apoB into account, allele-specific apo(a) levels were significantly associated with apoB levels and the apoB/apoA-1 ratio in African-Americans. The latter associations in African-Americans remained significant for allele-specific apo(a) levels for smaller apo(a) sizes (

While there has been considerable focus on the role and treatment of LDL cholesterol levels, a definitive role of triglycerides in the management of cardiovascular disease has been uncertain. Notably, with increasing triglyceride levels, there is a parallel increase in cholesterol levels carried by triglyceride-rich lipoproteins, which has prompted interest in the use of non-HDL cholesterol levels as a tool guiding interventions. Recent studies have provided evidence for an independent role of triglyceride levels as a cardiovascular risk factor, and recently, an Endocrine Society guideline was published for treatment of hypertriglyceridemia. In contrast to the relative uncertainty regarding triglycerides and cardiovascular disease, a role of very high triglyceride levels as a risk factor for pancreatitis has been well known. The present paper summarizes the underlying evidence for a risk role for triglyceride levels in cardiovascular disease and pancreatitis, current treatment recommendations and areas of future research.

Studies in animals have documented that, compared with glucose, dietary fructose induces dyslipidemia and insulin resistance. To assess the relative effects of these dietary sugars during sustained consumption in humans, overweight and obese subjects consumed glucose- or fructose-sweetened beverages providing 25% of energy requirements for 10 weeks. Although both groups exhibited similar weight gain during the intervention, visceral adipose volume was significantly increased only in subjects consuming fructose. Fasting plasma triglyceride concentrations increased by approximately 10% during 10 weeks of glucose consumption but not after fructose consumption. In contrast, hepatic de novo lipogenesis (DNL) and the 23-hour postprandial triglyceride AUC were increased specifically during fructose consumption. Similarly, markers of altered lipid metabolism and lipoprotein remodeling, including fasting apoB, LDL, small dense LDL, oxidized LDL, and postprandial concentrations of remnant-like particle-triglyceride and -cholesterol significantly increased during fructose but not glucose consumption. In addition, fasting plasma glucose and insulin levels increased and insulin sensitivity decreased in subjects consuming fructose but not in those consuming glucose. These data suggest that dietary fructose specifically increases DNL, promotes dyslipidemia, decreases insulin sensitivity, and increases visceral adiposity in overweight/obese adults.

The hypothesis was tested that plasma levels of adiponectin would be associated with coronary artery disease (CAD) across African-American and Caucasian ethnicity and gender. Adiponectin levels, cardiovascular risk factors, and extent of CAD were measured in 453 subjects (173 African-American and 280 Caucasian men and women). The distribution of adiponectin levels differed significantly between African-Americans and Caucasians (P

"hypertriglyceridemia represents a growing problem in the general population." [ABSTRACT FROM AUTHOR]

Aims In experimental studies parathyroid hormone (PTH) has been associated with underlying causes of heart failure (HF) such as atherosclerosis, left ventricular hypertrophy, and myocardial fibrosis. Individuals with increased levels of PTH, such as primary or secondary hyperparathyroidism patients, have increased risk of ischaemic heart disease and HF. Moreover, increasing PTH is associated with worse prognosis in patients with overt HF. However, the association between PTH and the development HF in the community has not been reported. Methods and Results In a prospective, community-based study of 864 elderly men without HF or valvular disease at baseline (mean age 71 years, the ULSAM study) the association between plasma (P)-PTH and HF hospitalization was investigated adjusted for established HF risk factors (myocardial infarction, hypertension, diabetes, electrocardiographic left ventricular hypertrophy, smoking, and hypercholesterolaemia) and variables reflecting mineral metabolism (S-calcium, S-phosphate, P-vitamin D, S-albumin, dietary calcium and vitamin D intake, physical activity, glomerular filtration rate, and blood draw season). During follow-up (median 8 years), 75 individuals were hospitalized due to HF. In multivariable Cox-regression analyses, higher P-PTH was associated with increased HF hospitalization (hazard ratio for 1-SD increase of PTH, 1.41, 95% CI 1.12–1.77, P = 0.003). Parathyroid hormone also predicted hospitalization in participants without apparent ischaemic HF and in participants with normal P-PTH. Conclusion In a large community-based sample of elderly men, PTH predicted HF hospitalizations, also after accounting for established risk factors and mineral metabolism variables. [ABSTRACT FROM AUTHOR]

Higher plasma fibrinogen levels are associated with increased risk of myocardial infarction in adults, but little is known about factors that influence fibrinogen levels in childhood. The authors examined the associations of measures of obesity, presence of the (G−455↑A) allele in theβ-fibrinogen promoter gene, and family history of early onset of ischemic heart disease with plasma fibrinogen levels in children. Children (n=299) were recruited during 1994–1997 from 276 families living in a racially mixed area of New York City. The mean age of the study children was 9.9 years; 79% were Hispanic. The frequency of the (G−455↑A) allele was lowere in Hispanics than in non-Hispanic Whites (15.5% vs. 28.3% in children (p<0.01) and 13.9% vs. 28.3% in parents (p<0.001). Graded relations of children‘s plasma fibrinogen levels were found with tertiles of body mass index (weight (kg)/heingt (m)2) and sum of skinfolds (tests for linear trend: p<0.001). Plasma fibrinogen levels in the children were not related to rece/ethnicity, presence of the (G−455↑!) allele, or family history. Multiple linear regression analyses adjusting plasma fibrinogen levels for age, sex race/ethnicity, the (G−455↑A) allele, and family history of early onset of heart disease showed a significant association with either body mass index or sum of skinfokis (p<0.001 for both models) but not with the other varlables. Am J Epidemiol 1999; 150: 737–46. [ABSTRACT FROM PUBLISHER]

Plasma levels of lipoprotein(a), Lp(a), is an independent risk factor for cardiovascular disease. Lp(a) has many properties in common with low-density lipoprotein (LDL), including a cholesteryl ester-rich lipid core and the presence of one copy of apolipoprotein B-100; both apoB-100 and the lipid core are pro-atherogenic. In addition, Lp(a) contains a unique hydrophilic, carbohydrate-rich protein, apo(a), linked to apoB through a single disulfide bond connecting the C-terminal regions of the two proteins. The similarities between apolipoprotein(a), apo(a), and plasminogen has initiated numerous studies on the possible role of Lp(a) as a prothrombotic agent. Studies to date suggest that Lp(a) has antifibrinolytic and procoagulant properties. In this review, we summarize recent studies focused on the interaction between Lp(a) and platelets. Collectively, results to date illustrate that thrombogenicity associated with Lp(a) could be due to risk associated with the LDL moiety, with the apo(a) moiety, or from the combination of those in Lp(a). Present findings suggest that the various components of Lp(a) may impact to a varying degree on different underlying pathways involved in platelet activation and aggregation. On balance, results indicate an effect by Lp(a) on platelet function and future studies focused on specific Lp(a) components, such as the role of apo(a) and of the LDL-like lipid moiety, are needed. [ABSTRACT FROM AUTHOR]

Background: Predictors of postprandial lipemia have not been explored in children. Objective: Our objective was to determine whether the postprandial triacylglycerol response is associated with low HDL-cholesterol and high fasting triacylglycerol concentrations and family history of early-onset ischemic heart disease (IHD) in children. Design: We administered a standardized fat load (52.5 g fat/m²) to 60 children (mean age: 14.0 y), 20 with and 40 without a family history of early-onset IHD, and to 29 mothers, all recruited from families enrolled in the Columbia University Biomarkers Study. Plasma lipid and retinyl palmitate concentrations were measured in the fasting state and 3, 6, and 8 h after the oral fat load. Results: In children, postprandial lipemia, as indicated by the incremental area under the triacylglycerol response curve, was associated with elevated fasting triacylglycerol concentrations (≥ 1.13 mmol/L; P < 0.01), with low fasting HDL-cholesterol concentrations (≤0.91 mmol/L; P < 0.01), and with the combination of low HDL-cholesterol and high triacylglycerol concentrations (P < 0.05). Family history of IHD, baseline LDL-cholesterol concentration, and apolipoprotein E genotype were not associated with the postprandial triacylglycerol or retinyl palmitate response. The mothers had fasting triacylglycerol concentrations similar to those of their children but a more prolonged response with higher triacylglycerol concentrations at 6 and 8 h (P < 0.01 and P < 0.05, respectively). Conclusions: In children, a delayed postprandial triacylglycerol response to a fat load is associated with the combination of high fasting triacylglycerol and low HDL-cholesterol concentrations. Predictors of postprandial triacylglycerol concentrations may be similar in children and adults. [ABSTRACT FROM AUTHOR]

Higher plasma fibrinogen levels are associated with increased risk of myocardial infarction in adultls, but little is known about factors that influence fibrinogen levels in childhood. The authors examined the associations of measures of obesity, presence of the (G−455→A) allele in theβ-fibrinogen promoter gene, and family history of early onset of ischemic heart disease with plasma fibrinogen levels in children. Children (n=299) were recruited during 1994–1997 from 276 families living in a racially mixed area of New York City. The mean age of the study children was 9.9 years; 79% were Hispanic. The frequency of the (G−455→A) allele was lowere in Hispanics than in non-Hispanic Whites (15.5% vs. 28.3% in children (p<0.01) and 13.9% vs. 28.3% in parents (p<0.001). Graded relations of children‘s plasma fibrinogen levels were found with tertiles of body mass index (weight (kg)/heingt (m)2) and sum of skinfolds (tests for linear trend: p<0.001). Plasma fibrinogen levels in the children were not related to rece/ethnicity, presence of the (G−455→A) allele, or family history. Multiple linear regression analyses adjusting plasma fibrinogen levels for age, sex race/ethnicity, the (G−455→A) allele, and family history of early onset of heart disease showed a significant association with either body mass index or sum of skinfokis (p<0.001 for both models) but not with the other varlables. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses an article within the issue that is a research on the development of atherosclerosis and the gene and the nutrient interactions.

In 2022, the European Atherosclerosis Society (EAS) published a new consensus statement on lipoprotein(a) [Lp(a)], summarizing current knowledge about its causal association with atherosclerotic cardiovascular disease (ASCVD) and aortic stenosis. One of the novelties of this statement is a new risk calculator showing how Lp(a) influences lifetime risk for ASCVD and that global risk may be underestimated substantially in individuals with high or very high Lp(a) concentration. The statement also provides practical advice on how knowledge about Lp(a) concentration can be used to modulate risk factor management, given that specific and highly effective mRNA-targeted Lp(a)-lowering therapies are still in clinical development. This advice counters the attitude: "Why should I measure Lp(a) if I can't lower it?". Subsequent to publication, questions have arisen relating to how the recommendations of this statement impact everyday clinical practice and ASCVD management. This review addresses 30 of the most frequently asked questions about Lp(a) epidemiology, its contribution to cardiovascular risk, Lp(a) measurement, risk factor management and existing therapeutic options. [Display omitted] [ABSTRACT FROM AUTHOR]

Background Atherosclerosis is a systemic disease. In patients with acute myocardial infarction (MI) the extent of polyvascular disease (PvD) is largely unknown. In this study we investigate the prevalence and clinical characteristics predictive of PvD in patients with non-ST-elevation (NSTEMI) and ST-elevation (STEMI) MI. Method 375 patients with acute MI included in the REBUS (Relevance of Biomarkers for Future Risk of Thromboembolic Events in Unselected Post-myocardial Infarction Patients) study were examined. Atherosclerotic changes were assessed in three arterial beds by coronary angiography, carotid ultrasound and ankle brachial index (ABI). Results compared findings of atherosclerosis in three arterial beds to fewer than 3 beds. PvD was defined as atherosclerosis in all three arterial beds. Results A medical history of MI, peripheral artery disease (PAD) or stroke was reported at admission in 17.9%, 2.1% and 3.7% of the patients, respectively. After evaluation, abnormal ABI was found in 20.3% and carotid artery atherosclerosis in 54.9% of the patients. In the total population, PvD was found in 13.8% of patients with no significant differences observed between NSTEMI and STEMI patients. Age (p < 0.001), diabetes (p = 0.039), previous PAD (p = 0.009) and female gender (p = 0.016) were associated with PvD. ABI was the most important predictor of PvD with a positive predictive value of 68.4% (95% CI 57.7–79.2%) and specificity of 92.4% (95% CI 89.5–95.4%). Conclusions PvD is underdiagnosed in patients suffering from MI, both NSTEMI and STEMI. ABI is a useful and simple measurement that appears predictive of widespread atherosclerosis in these patients. [ABSTRACT FROM AUTHOR]

The association of apolipoproteins A-I and B (apo A-I and apo B) with cardiovascular disease has been studied in younger populations, but there is sparse information in the elderly. We determined whether apo A-I and apo B were associated with carotid artery atherosclerosis (CAA) in 507 stroke-free elderly community residents (mean age 70.1±11.7 years, 60% women, 41% Hispanics, 30% African American, 28% Caucasian). CAA severity was normal (no plaque or carotid stenosis) in 39%, mild (maximum plaque thickness &les;1.8 mm or carotid stenosis <40%) in 25%, and moderate/severe (maximum plaque thickness >1.8 mm or carotid stenosis &ges;40%) in 36%. CAA severity increased with age in all race/ethnic groups (P<0.01). CAA was similar among African Americans and Caucasians, but less in Hispanics (age adjusted OR: 0.5, CI: 0.4–0.8). apo A-I <1.2 g/l (OR: 2.0, CI: 1.0–3.3) and apo B &ges;1.4 g/l (OR: 2.0, CI: 1.1–3.6) were associated with moderate–severe CAA. An apo B/apo A-I ratio &ges;1 was associated with moderate–severe CAA (OR: 2.4, CI: 1.3–4.4), and the association varied by race (Hispanics OR: 4.3, CI: 1.8–10; non-Hispanics, OR: 1.4, CI: 0.6–3.2). Total cholesterol, triglycerides and low density lipoprotein cholesterol were not associated with moderate–severe CAA, while high density lipoprotein cholesterol was protective (OR: 0.4, CI: 0.2–0.8). Thus, in an elderly population, apo A-I and B were determinants of moderate–severe CAA, and the degree of association varied by race/ethnicity [Copyright &y& Elsevier]

Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure. Background. Atherosclerotic cardiovascular disease and malnutrition are widely recognized as leading causes of the increased morbidity and mortality observed in uremic patients. C-reactive protein (CRP), an acute-phase protein, is a predictor of cardiovascular mortality in nonrenal patient populations. In chronic renal failure (CRF), the prevalence of an acute-phase response has been associated with an increased mortality. Methods. One hundred and nine predialysis patients (age 52 ± 1 years) with terminal CRF (glomerular filtration rate 7 ± 1 ml/min) were studied. By using noninvasive B-mode ultrasonography, the cross-sectional carotid intima-media area was calculated, and the presence or absence of carotid plaques was determined. Nutritional status was assessed by subjective global assessment (SGA), dual-energy x-ray absorptiometry (DXA), serum albumin, serum creatinine, serum urea, and 24-hour urine urea excretion. The presence of an inflammatory reaction was assessed by CRP, fibrinogen (N = 46), and tumor necrosis factor-α (TNF-α; N = 87). Lipid parameters, including Lp(a) and apo(a)-isoforms, as well as markers of oxidative stress (autoantibodies against oxidized low-density lipoprotein and vitamin E), were also determined. Results. Compared with healthy controls, CRF patients had an increased mean carotid intima-media area (18.3 ± 0.6 vs. 13.2 ± 0.7 mm2 , P < 0.0001) and a higher prevalence of carotid plaques &formmu1;. The prevalence of malnutrition (SGA 2 to 4) was 44%, and 32% of all patients had an acute-phase response (CRP ≥ 10 mg/liter). Malnourished patients had higher CRP levels (23 ± 3 vs. 13 ± 2 mg/liter, P < 0.01), elevated calculated intima-media area (20.2 ± 0.8 vs. 16.9 ± 0.7 mm2 , P < 0.01) and a higher prevalence of carotid plaques (90 vs. 60%, P < 0.0001) compared with well-nourished patients. During stepwise multivariate analysis adjusting for age and gender, vitamin E (P < 0.05) and CRP (P < 0.05) remained associated with an increased intima-media area. The presence of carotid plaques was significantly associated with age (P < 0.001), log oxidized low-density lipoprotein (oxLDL; P < 0.01), and small apo(a) isoform size (P < 0.05) in a multivariate logistic regression model. Conclusion. These results indicate that the rapidly developing atherosclerosis in advanced CRF appears to be caused by a synergism of different mechanisms, such as malnutrition, inflammation, oxidative stress, and genetic components. Apart from classic risk factors, low vitamin E levels and elevated CRP levels are associated with an increased intima-media area, whereas small molecular weight apo(a) isoforms and increased levels of oxLDL are associated with the presence of carotid plaques. [ABSTRACT FROM AUTHOR]

Apo(a)-isoform size, nutritional status and inflammatory markers in chronic renal failure. Atherosclerotic cardiovascular disease and malnutrition are widely recognized as leading causes of the increased morbidity and mortality observed in uremic patients. Levels of lipoprotein (a) [Lp(a)], an established cardiovascular risk factor, are elevated in uremic patients. Moreover, low serum albumin levels indicating malnutrition have been associated with elevated plasma Lp(a) levels in dialysis patients. However, serum albumin levels are also influenced by an inflammatory reaction. The present study was undertaken to further investigate the relationship between Lp(a), inflammation and malnutrition in patients with chronic renal failure (CRF) prior to the initiation of renal replacement therapy, and to investigate the potential relation between these factors and apo(a)-isoform size, an important determinant of plasma Lp(a) levels. A total of 83 patients (mean age 52 ± 1 year) with terminal (creatinine clearance 9 ± 1 ml/min) CRF were cross sectionally investigated. In addition to lipid parameters and apo(a)-isoform size, C-reactive protein (CRP), nutritional parameters including serum levels of albumin and body composition (dual energy x-ray absorptiometry), as well as a subjective global assessment (SGA) and the prevalence of cardiovascular disease (CVD) were evaluated. Malnourished patients (N = 39) had a significantly (P < 0.05) higher median plasma Lp(a) level (19.5 mg/dl) as compared to 44 well-nourished patients, (11.7 mg/dl). No difference was found for other lipid or lipoprotein parameters. A significant relationship was found between CRP and plasma Lp(a), whereas no significant relation was observed between plasma Lp(a) and serum albumin levels. The apo(a)-isoform distribution was similar among malnourished and well-nourished patients. There was no difference in nutritional parameters when comparing patients with small- and large-size apo(a)... [ABSTRACT FROM AUTHOR]