Family History Of Premature Atherosclerosis Research Articles

Genetic predisposition of metabolic syndrome independent of weight in premature atherosclerosis

Abstract Background Family history is a significant predictor of premature atherosclerotic cardiovascular events, which suggest that a genetic susceptibility underlies the development of premature atherosclerosis. Rather than the influence of single classic risk factors, such as hypertension, diabetes and dyslipidemia, these risk factors could be part of an underlying genetic insulin resistance or metabolic syndrome Methods Data on patients and their first degree family members visiting premature atherosclerosis clinic in a university medical centre, from 2007 until 2023 was analyzed. We divided them in controls (CACs=0 and Age >40 years), subclinical ASCVD (sASCVD) (CAC score ≥80th percentile) and premature ASCVD (PAS). We used principal component analysis (PCA) for clustering the predictor variables and generalized linear mixed model (GLMM) to analyze the mutual relationship between different clusters. The model performance was further validated in predicting the premature ASCVD. Result There were 1551 individuals divided across control (n=438), sASCVD (n=309) and PAS (804). We found 12 variables univariate significantly related to sASCVD. Using a principal component analysis (PCA) approach, these variables were loaded across 4 clusters which were defined as 1. Metabolic (elevated glucose or diabetes, elevated blood pressure or Hypertension, elevated Triglycerides, elevated waist circumference and elevated LDL-C); 2. Liver (elevated ALAT, elevated GGT, elevated triglycerides, decreased thrombocytes) 3. Inflammatory (decreased HDL-C, elevated Triglycerides and elevated leucocyte count) and 4. Lipid (elevated Lp(a) and elevated LDL-C). After mutual correction and model building, the metabolic (OR; 95% CI) (1.82; 1.48-2.27) and Liver clusters (1.20; 1.00-1.45) were only found to be significantly associated with risk of sASCVD. However, we did not find any association of inflammatory (1.19; 0.98-1.44) and lipid cluster (1.19; 0.99-1.41) with risk of sASCVD. Besides, association of these clusters with risk of sASCVD significantly varies among families suggested from variance of intercept when family was kept as a random effect in GLMM model and no interaction was noticed with BMI. We checked the performance of this model on premature atherosclerosis cohort and found model had a good discriminatory (AUC, 0.762; 0.735-0.790; P=0.001) ability for predicting PAS [Figure 1]. Conclusion In conclusion, our findings are suggestive of a significant association between metabolic syndrome factors and an increased risk of sASCVD in individuals with family history of premature atherosclerosis, regardless of weight. This association suggests the potential genetic predisposition towards premature atherosclerosis driving the observed metabolic parameters clustering in these individuals. Besides, the model demonstrated robust discriminatory power to predict premature atherosclerosis.ROC curve for premature atherosclerosis

SYNE1 gene novel variant is associated with myocardial infarction in young people with a family history of premature atherosclerosis

Abstract Introduction Genetic background is thought to be responsible for a family occurred premature atherosclerosis, including myocardial infarction (MI). Purpose The aim of the study was to investigate the role of genetic variants in young patients (aged <50 years) with MI and family history of premature atherosclerosis. Methods The studied group consisted of 70 patients aged 26-49 (mean 43.1, SD ±4.3), 17 women and 53 men, with MI and with family history of premature atherosclerosis, defined as MI or ischaemic stroke in first-degree relatives at age <65 years in women or <55 years in men. The mean BMI in the studied group was 28.8 kg/m2 (SD ±3.5), total cholesterol level 202.3 mg/dl (SD ±3.5), HDL 40.6 mg/dl (SD ±9.6), LDL 124.0 mg/dl (SD ±28.9), triglycerides 164.4 mg/dl (SD ±63.5), glucose 108.3 mg/dl (SD ±19.9) and creatinine 0.9 mg/dl (SD ±0.2). Regarding other risk factors 63 patients (90%) were smokers (mean 24.1 pack-years, SD ±13.0), 44 (62.8%) had hypertension, 11 (15.7%) had diabetes mellitus, and 8 (11.4%) had depression. All patients had diagnosed MI including MI with ST elevation (STEMI) in 18 cases (25.7%) and MI without ST elevation (NSTEMI) in 52 cases (74.3%). All patients, except 2 (no consent), had performed coronary angiography revealing 1-vessel coronary artery disease (VCAD) in 33 patients (47.1%), 2-VCAD in 17 patients (24.3%), and 3-VCAD in 20 patients (28.6%). The mean left ventricular ejection fraction (LVEF) was 51.8% (SD ±8.0). The total DNA has been extracted from whole peripheral blood samples. The targeted enrichment library was prepared and analyzed using New Generation Sequencing method on Hiseq4000, 2x150 cycles. Statistical analyses were performed using the R software package (www.r-project.org/). The results of sequencing were compared to data from the reference control population consisting of 597 healthy people (418 women, 179 men) aged 18-83 (mean 40.5, SD ± 12,4) as a whole and after matching with a studied group by age and gender in a proportion 1:3 (210 people, 51 women and 159 men, aged 18-77, mean 42.1, SD ±10.6) using Propensity Score Matching. Risks associated with detected variants were evaluated using Fisher’s exact test based on the allelic frequencies of variants in both groups. Results SYNE1 gene variant rs36215567 (NM_182961.4: c.20396+22A>G) has been detected in statistically significant higher incidence in the studied group in comparison to the control population (p=0.005) with OR=4,80 (95%CI 1,43-14,45) as well as when compared to the control population matched by age and gender (p=0.004) OR=9,31 (95%CI 1,64-95,41). There were no statistically significant differences in the incidence of familial hypercholesterolemia related gene variants: LDLR c.667G>A, PCSK9 c.658-36G>A, PCSK9 c.996+55C>A and APOB c.12382G>A between both cohorts. Conclusion A novel variant of SYNE1 gene is associated with myocardial infarction in young age patients with a family history of premature atherosclerosis.

Younger age of patients with myocardial infarction is associated with a higher number of relatives with a history of premature atherosclerosis

BackgroundPremature coronary artery disease is one of the most pressing global issues in modern cardiology. The aim of the study was to investigate the role of family history of premature cardiovascular disease (CVD) in patients aged < 50 years with myocardial infarction (MI) compared to that in patients aged ≥50 years with MI and to that in young people without MI (no-MI < 50).MethodsThe studied group (MI < 50) consisted of 240 patients aged 26–49 years with MI. The control groups consisted of 240 patients (MI ≥ 50) with MI aged 50–92 years and 240 healthy people aged 30–49 years without a history of MI (no-MI < 50).ResultsThere were statistically significant differences between the MI < 50 and MI ≥ 50 and no-MI < 50 groups regarding the family history of premature MI/ischaemic stroke and the percentage of patients with ≥2 relatives affected (10.8, 2.9, and 3.7%, respectively; p < 0.0001). There was a statistically significant difference in the patient age at the first MI occurrence among patients without a family history of premature CVD, those with 1 affected relative, and those with ≥2 affected first-degree relatives (56.6, 48.6 and 41.8 years, respectively) as well as those with affected first- and second-degree relatives (56.5, 50.7 and 47.0 years, respectively).ConclusionsA younger age of patients with myocardial infarction is associated with a higher number of relatives with a history of premature MI/ischaemic stroke. Thus, the family history of premature atherosclerosis involving not only first- but also second-degree relatives seems to be a valuable factor in CVD risk evaluation in young people.Graphical

Netrin-1 and the Grade of Atherosclerosis Are Inversely Correlated in Humans.

Netrin-1 has been shown to play a role in the initiation of atherosclerosis in mice models. However, little is known about the role of Netrin-1 in humans. We set out to study whether Netrin-1 is associated with different stages of atherosclerosis. Approach and Results: Plasma Netrin-1 levels were measured in different patient cohorts: (1) 22 patients with high cardiovascular risk who underwent arterial wall inflammation assessment using positron-emission tomography / computed tomography, (2) 168 patients with a positive family history of premature atherosclerosis in whom coronary artery calcium scores were obtained, and (3) 104 patients with chest pain who underwent coronary computed tomography angiography imaging to evaluate plaque vulnerability and burden. Netrin-1 plasma levels were negatively correlated with arterial wall inflammation (β, -0.01 [95% CI, 0.02 to -0.01] R2, 0.61; P<0.0001), and concentrations of Netrin-1 were significantly lower when atherosclerosis was present compared with individuals without atherosclerosis (28.01 versus 10.51 ng/mL, P<0.001). There was no difference in Netrin-1 plasma concentrations between patients with stable versus unstable plaques (11.17 versus 11.74 ng/mL, P=0.511). However, Netrin-1 plasma levels were negatively correlated to total plaque volume (β, -0.09 [95% CI, -0.11 to -0.08] R2, 0.57, P<0.0001), calcified plaque volumes (β, -0.10 [95% CI, -0.12 to -0.08] R2, 0.53; P<0.0001), and noncalcified plaque volumes (β, -0.08 [95% CI, -0.10 to -0.06] R2, 0.41; P<0.0001). Treatment of inflammatory stimulated endothelial cells with plasma with high Netrin-1 level resulted in reduced endothelial inflammation and consequently, less monocyte adhesion. Netrin-1 plasma levels are lower in patients with subclinical atherosclerosis and in patients with arterial wall inflammation. Netrin-1 is not associated with plaque vulnerability; however, it is negatively correlated to plaque burden, suggesting that Netrin-1 is involved in some, but not all, stages of atherosclerosis.

Cardiovascular Risk and Disease Among Masters Endurance Athletes: Insights from the Boston MASTER (Masters Athletes Survey To Evaluate Risk) Initiative.

BackgroundMasters athletes (MAs), people over the age of 35 that participate in competitive sports, are a rapidly growing population that may be uniquely at risk for cardiovascular (CV) disease. The objective of this study was to develop a comprehensive clinical CV profile of MA.MethodsAn electronic Internet-based survey (survey response rate = 66 %) was used to characterize a community cohort of MAs residing in Eastern Massachusetts, USA. Clinical and lifestyle factors associated with prevalent CV disease were determined using logistic regression.ResultsAmong 591 MAs (66 % men, age = 50 ± 9 years) with 21.3 ± 5.5 years of competitive endurance sport exposure, at least one CV risk factor was present in 64 % including the following: family history of premature atherosclerosis (32 %), prior/current tobacco exposure (23 %), hypertension (12.0 %), and dyslipidemia (7.4 %). There was a 9 % (54/591) prevalence of established CV disease which was accounted for largely by atrial fibrillation (AF) and coronary atherosclerosis (CAD). Prevalent AF was associated with years of exercise exposure [adjusted odds ratio, OR (95 % confidence intervals); OR = 1.10 (1.06, 1.21)] and hypertension [OR = 1.05 (1.01, 1.10)] while CAD was associated with dyslipidemia [OR = 9.09 (2.40, 34.39)] and tobacco use [OR = 1.78 (1.34, 3.10)] but was independent of exercise exposure.ConclusionsAmong MAs, AF is associated with prior exercise exposure whereas CAD is associated with typical risk factors including dyslipidemia and prior tobacco use. These findings suggest that there are numerous opportunities to improve disease prevention and clinical care in this population.

Atherosclerosis is Evident in Treated HIV-Infected Subjects With Low Cardiovascular Risk by Carotid Cardiovascular Magnetic Resonance

Premature atherosclerosis has been observed among HIV-infected individuals with high cardiovascular risk using one-dimensional ultrasound carotid intima-media thickness. We evaluated the assessment of HIV-infected individuals with low traditional cardiovascular disease risk using cardiovascular magnetic resonance, which allows three-dimensional assessment of the carotid artery wall. Carotid cardiovascular magnetic resonance was performed in 33 HIV-infected individuals (cases) (19 male, 14 female), and 35 HIV-negative controls (20 male, 15 female). Exclusion criteria included smoking, hypertension, hyperlipidemia (total cholesterol/HDL ratio > 5) or family history of premature atherosclerosis. Cases were stable on combination antiretroviral therapy with plasma HIV-1 RNA <50 copies per milliliter. Using computer modeling, the arterial wall, lumen, and total vessel volumes were calculated for a 4-cm length of each carotid artery centered on the bifurcation. The wall/outer-wall ratio (W/OW), an index of vascular thickening, was compared between the groups. Cases had a median CD4 cell count of 690 cells per microliter. Mean (±SD) age and 10-year Framingham coronary risk scores were similar for cases and controls (45.2 ± 9.7 years versus 46.9 ± 11.6 years and 3.97% ± 3.9% versus 3.72% ± 3.5%, respectively). W/OW was significantly increased in cases compared with controls (36.7% versus 32.5%, P < 0.0001); this was more marked in HIV-infected females. HIV status was significantly associated with increased W/OW after adjusting for age (P < 0.0001). No significant association between antiretroviral type and W/OW was found-W/OW lowered comparing abacavir to zidovudine (P = 0.038), but statistical model fits poorly. In a cohort of treated HIV-infected individuals with low measurable cardiovascular risk, we have observed evidence of premature subclinical atherosclerosis.

Analyses of C-Reactive Protein, Endothelial Nitric Oxide Synthase and Interleukin-6 Gene Polymorphisms in Adolescents with a Family History of Premature Coronary Artery Disease: A Pilot Study.

Family history of premature atherosclerosis imposes a high risk to people. The relationship between atherosclerosis and gene polymorphisms of various biomarkers such as Endothelial Nitric Oxide Synthase (eNOS), C-Reactive Protein (CRP), and Interleukin-6 (IL-6) has shown in previous studies. The major aim of the study was to evaluate the CRP, eNOS, and IL-6 gene polymorphisms in a group of adolescents who have a parental history of early coronary artery disease (CAD). Case-control study. Thirty-six volunteers with a father with obstructive CAD during the first four decades and 46 subjects with a father with normal coronary arteries documented with coronary angiography were included in the study. Polymerase chain reaction-restriction fragment length polymorphism techniques were used to analyze CRP, eNOS, and IL-6 polymorphisms. We did not find any differences between the two groups with regard to age, sex, body mass index, renal functions, systolic and diastolic blood pressures, lipid profile, and fasting glucose, hemoglobin, and high sensitivity CRP. A significant difference was only observed in IL-6-572 G/C genotype distribution and allele frequency between two groups (Pc=0.036 OR=3.48 CI (95%) 1.17-10.32). The present study showed a significant association between the IL-6-572 G/C gene polymorphism (presence of C allele) and adolescents with a parental history of premature CAD.

The assessment of cardiac autonomic functions in adolescents with a family history of premature atherosclerosis

OBJECTIVES:Subclinical atherosclerosis has been recently detected in adolescents with a family history of premature atherosclerosis. However, no studies in the literature have assessed the cardiac autonomic functions of these adolescents. The aim of this study was to evaluate the cardiac autonomic functions of adolescents with a family history of premature atherosclerosis compared with those of age- and gender-matched adolescents without a family history of atherosclerosis.METHOD:We evaluated the cardiac autonomic functions of 36 adolescents with a family history of premature atherosclerosis (Group 1) and compared them with those of 31 age- and gender-matched adolescents whose parents did not have premature atherosclerosis (Group 2). Twenty-four-hour time domain (standard deviation of all normal sinus RR intervals [SDNN], standard deviation of the mean of normal RR intervals in each 5-minute segment [SDANN], root-mean-square differences in successive RR intervals) and frequency domain (very low frequency, low frequency, high frequency, low frequency/high frequency) parameters of heart rate variability were used for the evaluation of cardiac autonomic functions.RESULTS:There were no differences in the time and frequency domain parameters of heart rate variability between the two groups. Heart rate was negatively correlated with SDNN (r = -0.278, p = 0.035), while age was significantly correlated with root-mean-square differences in successive RR intervals, high frequency, low frequency and low frequency/high frequency (r = -0.264, -0.370, 0.265 and 0.374, respectively; p<0.05 for all).CONCLUSION:We found that the cardiac autonomic functions of adolescents with a family history of premature atherosclerosis were not different compared with those of adolescents without a positive family history of premature atherosclerosis. It appears that subclinical atherosclerosis does not reach a critical value such that it can alter cardiac autonomic functions in adolescence.

Evaluation of possible subclinical atherosclerosis in adolescents with a family history of premature atherosclerosis

Evaluation of possible subclinical atherosclerosis in adolescents with a family history of premature atherosclerosis

Association between C-Reactive Protein, Endothelial Nitric Oxide Synthase, and Interleukin-6 Gene Polymorphisms in Adolescents with a Family History of Premature Atherosclerosis

PP-111 The aim of the study is to evaluate the gene polymorphisms in a group of adolescents with a family history of premature atherosclerosis. Thirty-six subjects who have a father with a history of obstructive coronary artery disease before the age 40 and 46 subjects who have a father with

Evaluation of possible subclinical atherosclerosis in adolescents with a family history of premature atherosclerosis

ObjectiveTo evaluate possible subclinical atherosclerosis using biomarkers and ultrasound-guided methods in a group of adolescents having fathers with premature atherosclerosis. MethodsThirty-three subjects whose fathers had a history of premature coronary artery disease and 30 counterparts whose fathers had no history of coronary artery disease were included in the study. ResultsThe homocysteine levels, high-sensitivity C-reactive protein levels, and cardiac chamber sizes and functions did not differ between the two groups. The carotid stiffness index β (CSI), the intima-media thickness (CIMT) and aortic pulse wave velocity (PWV) values were higher in the group with a family history of coronary artery disease, but only the difference in the CSI was statistically significant (CSI 3.07±1.33 vs 3.88±1.25, P=0.015; CIMT 0.53±0.09mm vs 0.57±0.08mm, P=0.068; PWV 3.49±0.53m/s vs 3.78±0.63m/s, P=0.053). ConclusionAmong several markers of subclinical atherosclerosis, the CSI was significantly higher in adolescents who had a family history of premature atherosclerosis. The small sample size, the multifactorial nature of atherosclerosis or the insufficient power of these methods may explain these results.

Acute myocardial infarction and pulmonary embolism in a young man with pernicious anemia-induced severe hyperhomocysteinemia

A 27 year-old man who presented to the hospital with progressive lower extremity weakness, developed an acute ST elevation myocardial infarction on his second hospital day. Primary angioplasty to the left anterior descending coronary artery was performed. Due to persistent dyspnea, the patient underwent a diagnostic chest computed tomography which confirmed multiple small pulmonary emboli. Laboratory analysis revealed a megaloblastic anemia with a reduced vitamin B12 level and positive titers for antibodies against intrinsic factor, establishing a diagnosis of pernicious anemia. Screening for hypercoaguable markers documented an isolated severely elevated homocysteine levels (105 μmol/l). No other significant risk factors for coronary artery disease including a family history of premature atherosclerosis were identified. This case illustrates the importance of testing for hyperhomocysteinemia as part of a workup for atherothrombotic disease, especially in patients without other significant risk factors. The severity of hyperhomocysteinemia found in our patient is unusual for patients with vitamin B12 malabsorption and raises the question of whether the widely practiced folic acid fortification in the United States may mask or even worsen vitamin B12 deficiency over time, leading to more severe cases of vitamin B12 deficiency and hyperhomocysteinemia than seen in the past.

Relationship Between Endothelial Function and Coronary Risk Factors in Patients With Stable Coronary Artery Disease

Results of experimental and clinical studies suggest that both coronary artery disease (CAD) itself and its traditional risk factors lead to endothelial dysfunction. The aim of the present study was to determine which CAD risk factors sustain their contribution to endothelial dysfunction despite the presence of established CAD. The study group comprised 150 patients with CAD. Using a high-resolution ultrasound, the diameter of the brachial artery at rest and during reactive hyperemia (flow-mediated dilatation, FMD%: endothelial-dependent stimulus to vasodilatation), as well as after sublingual administration of nitroglycerin (NTG%: endothelium-independent vasodilatation), was measured. The relationship between FMD% and coronary risk factors [diabetes mellitus (DM), total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, triglycerides, age, family history of premature atherosclerosis, smoking, hypertension (HT), body mass index (BMI)] was investigated. In univariate analysis there was an inverse relationship between FMD% and age (r=-0.300, p<0.001), and BMI (r=-0.230, p<0.005) and FMD% was significantly lower in diabetic patients when compared to non-diabetic patients (p<0.001). In stepwise multivariate regression analysis; FMD still correlated with DM and advanced age, but not with BMI (beta=0.065, p<0.001, beta=-0.001 p=0.002, beta=-0.087, p<0.284, respectively). FMD% was found to be not associated with hypercholesterolemia, family history of premature atherosclerosis, HT and smoking. Only aging and DM were independently associated with endothelial dysfunction in patients with established CAD.

Images in vascular medicine

A 47-year-old female was referred to the vascular center with a 15-year history of exertional bilateral calf pain with rapid resolution upon standing. She denied symptoms with weight-bearing or prolonged standing. Her symptoms were very reproducible at two flights of stairs or less than one block at a rapid pace. Cardiovascular risk factors included elevated total (236 mg=dl) and low density lipoprotein cholesterol (142 mg=dl). She otherwise denied tobacco exposure, diabetes mellitus, hypertension or a family history of premature atherosclerosis. Cardiovascular Panels A, B and C

Testing endothelial vasomotor function: nitric oxide, a multipotent molecule.

The initial description in 1980 by Furchgott and Zawadzki1 of endothelium-derived vasodilator factor has stimulated more than 2 decades of intense research to delineate the basic biology of the endothelium and its importance in the clinical setting.2 Endothelium-derived vasodilator factor has been identified as nitric oxide (NO).2 It is formed in endothelial cells from the amino acid l-arginine by endothelial isoform of NO synthase (eNOS), which is the product of the NOS3 gene.2,3 In addition to producing NO constitutively, the enzyme may be stimulated to increase NO synthesis by a variety of physiological agonists, shear stress, and pharmacological agents. Although discovered as a vasodilator, NO mediates many of the protective functions of the endothelium.4 It limits vascular recruitment of leukocytes by inhibiting the expression of proinflammatory cytokines, chemokines, and leukocyte adhesion molecules.2,4 It inhibits vascular smooth muscle proliferation and platelet adhesion and aggregation.2,4 NO also inhibits the production of tissue factor, a molecule that plays a critical role in the propensity of disrupted atherosclerotic plaques to cause intravascular thrombosis.5 In the setting of risk factors and experimental atherosclerosis, loss of the biological activity of endothelium-derived NO is accompanied by other alterations in endothelial phenotype that further increase the propensity for vasoconstriction, thrombosis, inflammation, and cellular proliferation in the vascular wall.6 Thus, endothelial dysfunction has the potential to contribute to key events in the course of human atherosclerosis. The experimental observations of Furchgott and others have stimulated translational research to elucidate the importance of endothelium-dependent vasodilation in human coronary atherosclerosis. Accordingly, Ludmer and colleagues7 administered the endothelium-dependent dilator acetylcholine into the coronary arteries of subjects undergoing cardiac catheterization. Acetylcholine induced dilation of normal epicardial coronary arteries but induced abnormal vasoconstriction, indicative of endothelial dysfunction, in patients with angiographic evidence of …

Folic acid improves arterial endothelial function in adults with hyperhomocystinemia

OBJECTIVESTo evaluate whether oral folic acid supplementation might improve endothelial function in the arteries of asymptomatic adults with hyperhomocystinemia.BACKGROUNDHyperhomocystinemia is an independent risk factor for endothelial dysfunction and occlusive vascular disease. Folic acid supplementation can lower homocystine levels in subjects with hyperhomocystinemia; however, the effect of this on arterial physiology is not known.METHODSAdults subjects were recruited from a community-based atherosclerosis study on healthy volunteers aged 40 to 70 years who had no history of hypertension, diabetes mellitus, hyperlipidemia, ischemic heart disease or family history of premature atherosclerosis (n = 89). Seventeen subjects (aged 54 ± 10 years, 15 male) with fasting total homocystine levels above 75th percentile (mean, 9.8 ± 2.8 μmol/liter) consented to participate in a double-blind, randomized, placebo-controlled and crossover trial; each subject received oral folic acid (10 mg/day) and placebo for 8 weeks, each separated by a washout period of four weeks. Flow-mediated endothelium-dependent dilation (percent increase in diameter) of the brachial artery was assessed by high resolution ultrasound, before and after folic acid or placebo supplementation.RESULTSCompared with placebo, folic acid supplementation resulted in higher serum folate levels (66.2 ± 7.0 vs. 29.7 ± 14.8 nmol/liter; p < 0.001), lower total plasma homocystine levels (8.1 ± 3.1 vs. 9.5 ± 2.5 μmol/liter, p = 0.03) and significant improvement in endothelium-dependent dilation (8.2 ± 1.6% vs. 6 ± 1.3%, p < 0.001). Endothelium-independent responses to nitroglycerin were unchanged. No adverse events were observed.CONCLUSIONFolic acid supplementation improves arterial endothelial function in adults with relative hyperhomocystinemia, with potentially beneficial effects on the atherosclerotic process.

Cardiovascular disease and risk factors in adults with hypopituitarism.

In 1992, Cuneo et al. (1992) reviewed, in this journal, the consequences of growth (GH) deficiency during adult life and coined the term ‘Growth hormone deficiency (GHD) syndrome in adults’. Limited information was available then on cardiovascular disease and risk factors in adults with hypopituitarism. More data have been published since on cardiovascular morbidity in symptom-free hypopituitary adults. Several groups have also published results on the effects of GH therapy on cardiac structure and function and on the cardiovascular risk factors. We shall review here the epidemiological and experimental data on cardiovascular morbidity and mortality in adult hypopituitarism. We shall also examine the prevalence of cardiovascular risk factors in this group of patients and their potential causes focusing on the possible role of GH deficiency and the effects of GH replacement.

Evolving lipoprotein risk factors: lipoprotein(a) and oxidized low-density lipoprotein

Cardiovascular disease is the leading cause of morbidity and mortality in Westernized populations. Evolving lipoprotein risk factors include LDL oxidation and lipoprotein(a) [lp(a)]. Several lines of evidence support a role for oxidatively modified LDL in atherogenesis and its in vivo existence. There are both direct and indirect measures of oxidative stress. The most relevant direct measure of lipid peroxidation is urinary F2 isoprostanes. The most common indirect measure of LDL oxidation is quantifying the lag phase of copper-catalyzed LDL oxidation by assaying conjugated diene formation. Lp(a) is increased in patients with cardiovascular and cerebrovascular disease. However, not all prospective studies have confirmed a positive relationship between Lp(a) and cardiovascular events. Lp(a) appears to present three major problems: standardization of the assay, establishing its role in atherogenesis, and the lack of an effective therapy that can substantially lower Lp(a) concentrations. Thus, at the present time, Lp(a) concentrations should not be recommended for the general population but be reserved for patients with coronary artery disease without established risk factors, young patients with coronary artery disease or cerebrovascular disease, or a family history of premature atherosclerosis and family members of an index patient with increased concentrations of Lp(a). Although both LDL oxidation and Lp(a) are evolving risk factors for cardiovascular disease, more data are needed before they become part of the established lipoprotein repertoire.

Lipoprotein Lp(a) Excess and Coronary Heart Disease

Lipoprotein Lp(a) excess has been identified as a powerful predictor of premature atherosclerotic vascular disease in several large, prospective studies. Lipoprotein Lp(a) levels modulate the risk of coronary heart disease in patients with hypercholesterolemia, and lipoprotein Lp(a) excess is commonly detected in men and women with premature coronary atherosclerosis. Lipoprotein Lp(a) contributes to atherothrombotic risk by multiple mechanisms that include impaired fibrinolysis, increased cholesterol deposition in the arterial wall, and enhanced oxidation of low density lipoprotein cholesterol. Although low density lipoprotein cholesterol reduction is the primary intervention in patients with lipoprotein Lp(a) excess, specific therapy to lower lipoprotein Lp(a) may be indicated for patients with premature coronary atherosclerosis, a strong family history of premature atherosclerosis, or refractory hypercholesterolemia. In consideration of the high prevalence of lipoprotein Lp(a) excess in patients with premature coronary heart disease and the intricate role of lipoprotein Lp(a) in atherothrombosis, this review provides an evidence-based approach to the screening and treatment of patients with lipoprotein Lp(a) excess.

Oxidized low-density lipoprotein and atherosclerosis

Atherosclerosis is the leading cause of morbidity and mortality in western society. The most important risk factors for atherosclerosis include smoking, hypertension, dyslipidemia, diabetes and a family history of premature atherosclerosis. Several studies indicate that an increased plasma low density lipoprotein (LDL) cholesterol constitutes a major risk factor for atherosclerosis. Many data support a proatherogenic role for oxidized LDL, and its in vivo existence. The oxidative susceptibility of LDL is increased with established cardiovascular risk factors, such as diabetes, smoking and dyslipidemia. Supplementation with antioxidants such as ascorbate and alpha to copherol can decrease LDL oxidation as well as cardiovascular mortality and thus shows promise in the prevention of atherosclerosis