Electrochemical immunosensing of low-density lipoprotein based on sol-gel encapsulation

Abstract Lipoprotein monitoring is desirable in the management of medical conditions such as atherosclerotic cardiovascular disease and coronary artery disease, in which controlling the concentration of these chylomicrons is crucial. Current clinical methods are complex and present poor reproducibility between laboratories. For these reasons, recent guidelines discard the assessment of low-density lipoprotein cholesterol (LDL-C) as a routine analysis during lipid-lowering therapies. Concerning the importance of monitoring this parameter, the authors present an electrochemical immunosensor constructed from a simple and easy-to-reproduce platform that allows detecting and quantifying LDL nanoparticles directly from human serum samples. The performance of the biosensor was studied by scanning electron microscopy, cyclic voltammetry, and electrochemical impedance spectroscopy. The biosensing platform displays good stability and linearity between 30 mg dL-1 and 135 mg dL-1 with a detection limit of 20 mg dL-1. The proposed biosensor can be easily employed for monitoring LDL concentration in clinical treatments.

Relationship between C -reactive protein and other cardiovascular risk factors in hypercholesterolemic individ alsa / Relação entre a proteína C reativa e os fatores de risco para doenças cardiovasculares em indivíduos hipercolesterolêmicos

Objective: To evaluate the correlation between ultrasensitive C-reactive protein (us-CRP) and markers of cardiovascular risk in hypercholesterolemic adults of differing nutritional status. Methods: Forty-six hypercholesterolemic subjects (7 men: 30 to 70 years; 39 women: 45 to 70 years) with total cholesterol >240 mg/dL were studied. Anthropometric variables (weight, height, and waist and hip circumference) were measured, as well as us-CRP, total cholesterol (TC), HDL-C, LDL-C, VLDL-C, triglycerides, apolipoprotein AI, apolipoprotein B, glucose and fasting insulin, and homeostasis model assessment (HOMA-IR) of insulin resistance. Spearman correlations and multiple linear regression analysis were performed at a level of significance of 5%. Results: Plasma levels of triglycerides, VLDL-C, glucose, HDL-C and us-CRP were higher in overweight subjects (p<0.05). Ultrasensitive CRP was positively correlated with body mass index (r=0.32) and hip circumference (r=0.30), as well as with TC (r=0.33), apolipoprotein B (r=0.36) and glucose (r=0.42). Regression analysis showed that us-CRP concentration was positively associated with TC, glucose, and waist-hip ratio. These parameters explained 41% of the variability in us-CRP. Conclusion: Obese individuals present a higher concentration of us-CRP, fasting glucose, triglycerides, and VLDL-C. Excess weight is associated with us-CRP, a finding highlighting the importance of this biomarker for the detection of individuals at cardiovascular risk.

Objetivo: Avaliar a correlação entre a proteína C reativa ultrasensível (PCR-us) e os marcadores clássicos de risco cardiovascular em adultos hipercolesterolêmicos em diferentes estados nutricionais. Métodos: Amostra de 46 indivíduos hipercolesterolêmicos (7 homens: 30 a 70 anos e 39 mulheres: 45 a 70 anos) com colesterol total (CT) >240 mg/dL. Realizou-se determinações antropométricas como peso, altura, circunferência da cintura (CC) e do quadril (CQ), além de medidas plasmáticas de PCR-us, CT, HDL-C, LDL-C, VLDL-C, triglicerídeos (TG), apolipoproteína AI (Apo AI), apolipoproteína B (Apo B), glicose e insulina de jejum e HOMA-IR. Realizou-se correlações de Spearman e análise de regressão linear múltipla ao nível de significância de 5%. Resultados: Os níveis plasmáticos de TG, VLDL-C, glicose, HDL-C e PCR-us foram maiores em indivíduos com sobrepeso (p<0,05). A PCR-us foi positivamente correlacionada com o índice de massa corporal (r=0,32) e com a CQ (r=0,30), bem como com o CT (r=0,33), Apo B (r=0,36) e glicose (r=0,42). A análise de regressão mostrou que a concentração de PCR-us foi positivamente associada ao CT, glicose e razão cintura-quadril. Esses parâmetros explicam a variabilidade da PCR-us em 41%. Conclusão: Os indivíduos obesos têm maior concentração plasmática de PCR-us, glicose, TG e VLDL-C. O excesso de peso está correlacionado com a PCR-us, mostrando a importância deste biomarcador para triagem de indivíduos de risco cardiovascular.

Evaluación del riesgo cardiovascular en trabajadores de institución financiera de la ciudad de Guatemala / Evaluation of the cardiovascular risk in workers of financial institution of the city of Guatemala

Las enfermedades cardiovasculares son una epidemia a nivel mundial y en países en vías de desarrollo, laincidencia y prevalencia han ido en aumento. Objetivo: El objetivo general fue determinar la prevalencia defactores de riesgo para el desarrollo de enfermedad cardiovascular en un grupo de personas económicamente activas. Métodos: Estudio descriptivo transversal que incluyó a todos los trabajadores de la institución que voluntariamente dieron una muestra de sangre y de orina, y se sometieron a una evaluación clínica durante los meses de junio de 2011 a julio del 2012. Resultados: incluimos 532 participantes, edad promedio 38años(19-65años), 69% de sexo masculino, 23% hipertensión arterial, 7% pre-hipertensión, 8% de tabaquismo, obesidad 16%, 36% sobrepeso, 35% hipercolesterolemia, 31% hipertrigliceridemia, 59% HDL<40mg/dl, 62% LDL >100mg/dl, glicemia preprandial alterada 4%, 14% hiperuricemia, 1% muy alto riesgocardiovascular, 17% alto riesgo. Conclusiones: Los factores de riesgo cardiovascular tienen una alta prevalencia en la población de estudio, a pesar de tratarse de una población joven.

Cardiovascular diseases are epidemic globally and in developing countries, the incidence and prevalence have increased. Objective: The objective was to determine the prevalence of risk factors for the development of cardiovascular disease in a group of economically active people. Methods: A cross sectional study that included all employees of the institution who voluntarily gave a blood sample and urine, and underwent a clinical evaluation during the months of June 2011 to July 2012. Results: We included 532 participants, meanage 38years (19-65años), 69%male, 23% hypertension, pre hypertension 7%, 8% smoking, obesity16%,36% overweight, 35% hypercholesterolemia, hypertriglyceridemia 31%, 59%HDL <40mg/dL, 62%LDL> 100mg/dl, altered fasting glucose4%, 14% hyperuricemia, 1% very high cardiovascular risk, 17% higher risk. Conclusions: Cardiovascular risk factors are highly prevalent in the study population, despite being a young population.

Audit of accuracy of clinical coding in oral surgery.

We aimed to study the accuracy of clinical coding within oral surgery and to identify ways in which it can be improved. We undertook did a multidisciplinary audit of a sample of 646 day case patients who had had oral surgery procedures between 2011 and 2012. We compared the codes given with their case notes and amended any discrepancies. The accuracy of coding was assessed for primary and secondary diagnoses and procedures, and for health resource groupings (HRGs). The financial impact of coding Subjectivity, Variability and Error (SVE) was assessed by reference to national tariffs. The audit resulted in 122 (19%) changes to primary diagnoses. The codes for primary procedures changed in 224 (35%) cases; 310 (48%) morbidities and complications had been missed, and 266 (41%) secondary procedures had been missed or were incorrect. This led to at least one change of coding in 496 (77%) patients, and to the HRG changes in 348 (54%) patients. The financial impact of this was £114 in lost revenue per patient. There is a high incidence of coding errors in oral surgery because of the large number of day cases, a lack of awareness by clinicians of coding issues, and because clinical coders are not always familiar with the large number of highly specialised abbreviations used. Accuracy of coding can be improved through the use of a well-designed proforma, and standards can be maintained by the use of an ongoing data quality assurance programme.

Hyper-betalipoproteinemia LDL 1,2: a newly identified nonatherogenic hypercholesterolemia in a group of hypercholesterolemic subjects.

OBJECTIVE: The identification of a non-atherogenic and an atherogenic lipoprotein profile, non-athero phenotype A vs. athero phenotype B, in a group of hypercholesterolemic subjects reveals newly discovered non-atherogenic hypercholesterolemia. Individuals with this type of hypercholesterolemia, or hyper-betalipoproteinemia LDL1,2, are probably not at increased risk to develop a premature atherothrombosis or a sudden cardiovascular event. Examined individuals with hyper-betalipoproteinemia LDL1,2 were divided into two subgroups: individuals under 40 years of age, and older individuals between 46 and 71 years of age. Subjects in the under 40 years of age group did not have any apparent clinical or laboratory-proven impairment of the cardiovascular system. The older subjects with hyper-betalipoproteinemia and a non-atherogenic lipoprotein profile had only mild signs of clinically irrelevant aortic valve sclerosis. METHODS: A quantitative analysis of the lipoprotein spectrum in plasma in a group of hypercholesterolemic subjects was performed. An innovative electrophoresis method on polyacrylamide gel (PAG) was used for the analysis of plasma lipoproteins and for the identification of atherogenic vs. non-atherogenic lipoproteins in plasma. With regard to lipids, total cholesterol and triglycerides in plasma were analyzed with an enzymatic CHOD PAP method (Roche Diagnostics, FRG). A new parameter, the score for anti-atherogenic Risk (SAAR), was calculated as the ratio between non-atherogenic to atherogenic plasma lipoproteins in the examined subjects. RESULTS: There was a high concentration of LDL1, and LDL2 subfractions (p<0.0001), and an extremely low concentration of LDL3-7 (p<0.0001) in the non-atherogenic lipoprotein profile of hyper-betalipoproteinemia LDL1,2 compared to the control group. Higher concentrations (p<0.0001) of lipids and lipoproteins in the non-atherogenic hypercholesterolemia, compared to the control group, were also found. The hyper-betalipoproteinemia LDL1,2 was also characterized by high SAAR values. There was found a higher concentration of HDL large and HDL intermediate subfractions in hypercholesterolemic subjects. CONCLUSIONS: The advantages of this new diagnostic method include: (i) identification of the existence of a non-atherogenic hyper-betalipoproteinemia LDL1,2 in examined hypercholesterolemic subjects with untreated hypercholesterolemia (ii) introduction of a new risk measure, the score for anti-atherogenic risk (SAAR), for the estimation of atherogenic/anti-atherogenic risk. (iii) the presence of small dense LDL in plasma is decisive for the declaration of an atherogenic lipoprotein profile. It is valid for hyperlipidemia and for normolipidemia as well.

Local and systemic biomarkers in gingival crevicular fluid increase odds of periodontitis.

AIM: To determine the independent and combined associations of interleukin-1beta (IL-1beta) and C-reactive protein (CRP) in gingival crevicular fluid (GCF) on periodontitis case status in the Australian population. MATERIALS AND METHODS: GCF was collected from 939 subjects selected from the 2004-2006 Australian National Survey of Adult Oral Health: 430 cases had examiner-diagnosed periodontitis, and 509 controls did not. IL-1beta and CRP in GCF were detected by enzyme-linked immunosorbent assays. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated in bivariate and stratified analysis and fully adjusted ORs were estimated using multivariate logistic regression. RESULTS: Greater odds of having periodontitis was associated with higher amounts of IL-1beta (OR=2.4, 95% CI=1.7-3.4 for highest tertile of IL-1beta relative to lowest tertile) and CRP (OR=1.9, 95% CI=1.5-2.5 for detectable CRP relative to undetectable CRP). In stratified analysis, there was no significant interaction between biomarkers (p=0.68). In the multivariate analyses that controlled for conventional periodontal risk factors, these relationships remained (IL-1beta OR=1.8, 95% CI=1.1-2.6; CRP OR=1.7, 95% CI=1.3-2.3). CONCLUSIONS: Elevated odds of clinical periodontitis was associated independently with each biomarker. This suggests that people with elevated biomarkers indicative of either local (IL-1beta) or systemic (CRP) inflammation are more likely to suffer from periodontal disease.

Reclassification of patients for aggressive cholesterol treatment: additive value of multislice coronary angiography to the National Cholesterol Education Program guidelines.

BACKGROUND: National Cholesterol Education Program (NCEP) guidelines have been used to define treatment goals in patients with hypercholesterolemia. However, epidemiology-based guidelines are unable to identify all subjects with coronary artery disease for aggressive lipid intervention. OBJECTIVE: We sought to evaluate the additive value of multislice computed tomography (MSCT) angiography to the NCEP guideline classification for lipid treatment. METHODS: Multislice computed tomography was performed in 114 consecutive patients (mean age 57+/-14 y; 59% male) without known coronary artery disease. Subjects were classified into 3 categories (low-, intermediate-, and high-risk) according to their Framingham risk scores (FRS). RESULTS: Traditional cardiac risk factors were common: hypertension 59%, diabetes 13%, and smoking 22%. On the basis of the FRS, 11% (n=12/114) of the patients met high-risk criteria requiring aggressive cholesterol reduction. Of those in the low- and intermediate-risk groups, MSCT found coronary plaque in 76% (n=77/102), with moderate or severe plaque in 38% (n=39/102), thus reclassifying them in the high-risk category. Use of statin drugs increased from 32% at baseline to 53% (p=0.002) based on MSCT results; statin dose was increased in 31% of the patients who were already on a statin. The mean low-density lipoprotein cholesterol (LDL-c) decreased from 114 mg/dL to 91 mg/dL after MSCT (p<0.001). CONCLUSION: Multislice computed tomography reclassifies a high percentage of patients considered to be low- to intermediate-risk into the high-risk category based on their coronary artery lesions. Thus, the rise in MSCT use at present may have a large impact on clinician practice patterns in lipid-lowering therapy.

Risk and disease.

The way that diseases such as high blood pressure (hypertension), high cholesterol, and diabetes are defined is closely tied to ideas about modifiable risk. In particular, the threshold for diagnosing each of these conditions is set at the level where future risk of disease can be reduced by lowering the relevant parameter (of blood pressure, low-density lipoprotein, or blood glucose, respectively). In this article, I make the case that these criteria, and those for diagnosing and treating other "risk-based diseases," reflect an unfortunate trend towards reclassifying risk as disease. I closely examine stage 1 hypertension and high cholesterol and argue that many patients diagnosed with these "diseases" do not actually have a pathological condition. In addition, though, I argue that the fact that they are risk factors, rather than diseases, does not diminish the importance of treating them, since there is good evidence that such treatment can reduce morbidity and mortality. For both philosophical and ethical reasons, however, the conditions should not be labeled as pathological. The tendency to reclassify risk factors as diseases is an important trend to examine and critique.

Who exceeds ATP-III risk thresholds? Systematic examination of the effect of varying age and risk factor levels in the ATP-III risk assessment tool.

OBJECTIVE: We sought to determine the levels of risk factors required to exceed threshold values of intermediate (> or = 10%) or high (> 20%) predicted 10-year risk for coronary heart disease using the Adult Treatment Panel III (ATP-III) Risk Assessment Tool. METHODS: Continuous risk factor values were entered into the risk assessment tool to examine levels of predicted 10-year risk. Both individual risk factors and the joint effects of varying multiple risk factors were systematically examined. RESULTS: Women only exceed 10% risk at ages > or = 70 with single risk factors of HDL-cholesterol levels < 30 mg/dL or systolic blood pressure > 170 mm Hg. Women < or = 65 only exceed 10% risk if they are smokers with low HDL-cholesterol levels. In contrast, single risk factors can cause men over 45 to exceed 10% or 20% predicted 10-year risk. Combinations of only modestly elevated risk factors cause many men to exceed 10% risk at ages > or = 45, and to exceed 20% risk at ages > or = 55. CONCLUSIONS: Because such high-risk factor levels are required for men < 45 years and women < 65 years to exceed ATP-III risk thresholds, additional means for risk communication may be needed for individuals with elevated risk factors in these age ranges.

Importance of acyl-coenzyme A:cholesterol acyltransferase 1/2 dual inhibition for anti-atherosclerotic potency of pactimibe.

Pactimibe sulfate, [7-(2,2-dimethylpropanamido)-4,6-dimethyl-1-octylindolin-5-yl]acetic acid hemisulfate, a novel Acyl-coenzyme A:cholesterol acyltransferase (ACAT) inhibitor, was investigated in vitro and in vivo to characterize its potential. Pactimibe exhibited dual inhibition for ACAT1 and ACAT2 (concentrations inhibiting 50% [IC50s] at micromolar levels) more potently than avasimibe. Kinetic analysis revealed pactimibe is a noncompetitive inhibitor of oleoyl-CoA (Ki value: 5.6 microM). Furthermore, pactimibe markedly inhibited cholesteryl ester formation (IC50: 6.7 microM) in human monocyte-derived macrophages, and inhibited copper-induced oxidation of low density lipoprotein more potently than probucol. Pactimibe exerted potent lipid-lowering and anti-atherosclerotic effects in atherogenic diet-fed hamsters. At doses of 3 and 10 mg/kg for 90 days, pactimibe decreased serum total cholesterol by 70% and 72%, and aortic fatty streak area by 79% and 95%, respectively. Despite similar cholesterol lowering, fatty streak area reduction was greater by 10 mg/kg. These results suggest that ACAT1/2 dual inhibitor pactimibe has anti-atherosclerotic potential beyond its plasma cholesterol-lowering activity.

Differential effect of two nicotinic acid preparations on low-density lipoprotein subclass distribution in patients classified as low-density lipoprotein pattern A, B, or I.

We tested the hypothesis that treatment with nicotinic acid results in a differential blood lipid response in subjects classified as having a low-density lipoprotein (LDL) pattern A or B. One hundred eighty hypercholesterolemic subjects were randomized to placebo (n = 61), immediate-release niacin (3,000 mg/day, n = 59), or extended-release niacin (1,500 mg/day, n = 60) for 14 weeks. Lipids and lipoprotein cholesterol were determined with enzymatic methods. LDL subclass distribution was determined with 2% to 16% polyacrylamide gradient gel electrophoresis. Extended- and immediate-release niacin had significant effects on the decrease of triglycerides, total cholesterol, LDL cholesterol, apoprotein B, lipoprotein(a), and apoprotein A-I and significantly increased high-density lipoprotein cholesterol. The 2 nicotinic acid compounds and doses significantly increased mean LDL peak particle diameter and percent distribution in large LDL I and IIa, with a significant decrease in small LDL IIIa, IIIb, and IVb. In patients with LDL pattern B compared with those with pattern A, extended-release niacin (1,500 mg/day) increased LDL peak particle diameter significantly more and decreased the percent distributions of small LDL IIIa, LDL IIIb, and LDL IVa significantly more. With 3,000 mg/day, immediate-release nicotinic acid in patients with LDL pattern B exhibited a significantly greater increase in LDL peak particle diameter and large LDL IIa and IIb and significantly greater decreases in small LDL IIIa, IIIb, and IVa compared with patients with pattern A. These differences in response between patients with LDL pattern A and those with pattern B were not reflected by changes in the standard lipid profile, including apoproteins A-I and B. Nicotinic acid has a significantly different effect on lipids and lipoprotein subclass distribution in subjects classified as having LDL subclass pattern A or B. Nicotinic acid has a significantly greater effect on the decrease of small LDL subclass distribution and increase in LDL peak particle diameter in pattern B versus pattern A.

Comparison of effects on low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with rosuvastatin versus atorvastatin in patients with type IIa or IIb hypercholesterolemia.

This randomized, double-blind, placebo-controlled trial was conducted in 52 centers in North America to compare the effects of the new, highly effective statin, rosuvastatin, with atorvastatin and placebo in hypercholesterolemic patients. After a 6-week dietary run-in, 516 patients with low-density lipoprotein (LDL) cholesterol > or =4.14 mmol/L (160 mg/dl) and < 6.47 mmol/L (250 mg/dl) and triglycerides < or =4.52 mmol/L (400 mg/dl) were randomized to 12 weeks of once-daily placebo (n = 132), rosuvastatin 5 mg (n = 128), rosuvastatin 10 mg (n = 129), or atorvastatin 10 mg (n = 127). The primary efficacy end point was percent change in LDL cholesterol. Secondary efficacy variables were achievement of National Cholesterol Education Program (NCEP) Adult Treatment Panel II (ATP II), ATP III, and European Atherosclerosis Society LDL cholesterol goals and percent change from baseline in high-density lipoprotein (HDL) cholesterol, total cholesterol, triglycerides, non-HDL cholesterol, apolipoprotein B, and apolipoprotein A-I. Rosuvastatin 5 and 10 mg compared with atorvastatin 10 mg were associated with greater LDL cholesterol reductions (-40% and -43% vs 35%; p <0.01 and p <0.001, respectively) and HDL cholesterol increases (13% and 12% vs 8%, p <0.01 and p <0.05, respectively). Total cholesterol and apolipoprotein B reductions and apolipoprotein A-I increases were also greater with rosuvastatin; triglyceride reductions were similar. Rosuvastatin 5 and 10 mg were associated with improved achievement in ATP II (84% in both rosuvastatin groups vs 73%) and ATP III (84% and 82% vs 72%) LDL cholesterol goals, and rosuvastatin 10 mg was more effective than atorvastatin in achieving European Atherosclerosis Society LDL cholesterol goals. Both treatments were well tolerated.

Effects of policosanol in older patients with type II hypercholesterolemia and high coronary risk.

BACKGROUND: The present study was undertaken to investigate the effects of policosanol in older patients with type II hypercholesterolemia and more than one concomitant atherosclerotic risk factor. METHODS: After 6 weeks on a lipid-lowering diet, 179 patients randomly received a placebo or policosanol at doses of 5 followed by 10 mg per day for successive 12-week periods of each dose. Policosanol (5 and 10 mg/d) significantly (p < .001) reduced low-density lipoprotein cholesterol (LDL-C; 16.9% and 24.4%, respectively) and total cholesterol (TC; 12.8% and 16.2%, respectively), while significantly (p < .01) increasing (p < .001) high-density lipoprotein cholesterol (HDL-C) by 14.6% and 29.1%, respectively. RESULTS: Policosanol significantly decreased (p < .01) the ratios of LDL-C to HDL-C (29.1%) and TC to HDL-C (28%) at study completion, although triglycerides remained unchanged. Policosanol, but not the placebo, significantly improved (p .01) cardiovascular capacity, which was assessed using the Specific Activity Scale. No serious adverse experiences occurred in policosanol patients (p < .01), compared with seven adverse experiences (7.9%) reported by placebo patients. CONCLUSIONS: This study shows that policosanol is effective, safe, and well tolerated in older hypercholesterolemic patients.

Effect of combined fluvastatin-fenofibrate therapy compared with fenofibrate monotherapy in severe primary hypercholesterolemia. French Fluvastatin Study Group.

This double-blind study was designed to assess the efficacy and safety of fluvastatin-fenofibrate combination therapy compared with fenofibrate monotherapy in severe primary hypercholesterolemia (low-density lipoprotein [LDL] cholesterol > or =190 mg/dl [4.9 mmol/L], triglycerides < or =350mg/dl [3.9 mmol/l]). After a 10-week placebo and dietary baseline period, 102 patients were randomized to receive micronized fenofibrate 200 mg, fluvastatin 20 mg plus micronized fenofibrate 200 mg, or fluvastatin 40 mg plus micronized fenofibrate 200 mg. At week 16, fenofibrate 200 mg alone lowered LDL cholesterol from baseline by 21% compared with 32% for fluvastatin 20 mg plus fenofibrate 200 mg and 41% for fluvastatin 40 mg plus fenofibrate 200 mg (p <0.001). Triglycerides decreased by 29% with fenofibrate 200 mg alone, 39% with fluvastatin 20 mg plus fenofibrate 200 mg, and 40% with fluvastatin 40 mg plus fenofibrate 200 mg (p <0.05). Safety was assessed by recording adverse events and measuring clinical laboratory parameters. The adverse event profile was similar for the 3 treatment groups. One patient withdrew due to an increase in transaminase levels. No significant increase in creatine phosphokinase levels was observed with combination therapy. In conclusion, the addition of fluvastatin to micronized fenofibrate results in substantial improvement in atherogenic plasma lipids and is well tolerated.

Lipid levels. Applying the second National Cholesterol Education Program report to geriatric medicine.

Aging is accompanied by increases in cholesterol levels that increase the risk of atherosclerosis, coronary heart disease, and stroke. A large body of evidence shows that lipid lowering can reduce the incidence of vascular-related events. Guidelines for the management of hypercholesterolemia were outlined in the second National Cholesterol Education Program report (Adult Treatment Panel II). According to ATPII, the first step is to identify individuals at risk for vascular disease and those with borderline-high or high cholesterol levels. Screening for hyperlipidemia should continue beyond age 65 if the individual patient would benefit from long-term lipid management. Primary and secondary interventions consist of dietary therapy, exercise, and pharmacotherapy, based on the individual patient's risk factors.

Mild hypercholesterolemia and premature heart disease: do the national criteria underestimate disease risk?

OBJECTIVES: To determine the frequency of hospital admissions for acute coronary syndrome in young adults and to examine the risk factors that predispose to the development of premature heart disease. BACKGROUND: Significant coronary heart disease (CHD) is considered rare in the young adult. Current guidelines do not recommend treatment of mild cholesterol abnormalities for primary prevention of CHD in the young. METHODS: This is a large case series of 449 adults (< or =50 years) admitted to the hospital with acute coronary syndrome. A history of cardiovascular risk factors and lipid profile were recorded. The presence and extent of CHD were established. RESULTS: Mean patient age was 44 +/- 6 years. Documented CHD was present in 61% of hospital admissions. Multivariate analysis revealed that history of hypercholesterolemia, history of smoking and diabetes were independently associated with premature CHD. The fasting lipid profiles were only borderline to mildly abnormal. Serum total cholesterol, low-density lipoprotein (LDL) and triglyceride levels were not different in cases compared with control subjects. Nearly half (49%) of those with LDL levels of > or =160 mg/dl had only one additional risk factor or none. Despite this, a history of hypercholesterolemia had independent and incremental value on other risk factors for the likelihood of premature CHD. CONCLUSIONS: The magnitude of hospital admissions relating to premature CHD is high. In this population, the presence of borderline or mild hypercholesterolemia has significant effects on the development of premature CHD. These observations have significant implications in the development of guidelines for primary prevention of premature CHD.