Elevated LDL-C Research Articles

Sports Requiring Stressful Physical Exertion Cause Abnormalities in Plasma Lipid Profile

To study the effect of different types of sports on plasma lipid profile. Subjects and method. Fasting plasma levels of total, LDL- and HDL-cholesterol (TC, LDLc, HDLc), triglycerides, phospholipids, apo A-I, apo B-100, and Lp(a) were measured in 28 swimmers, 17 volleyball players and 23 soccer players, and in a control group. All subjects participated in official national competitions except the control group. The results were compared to those in a control group of 26 healthy sedentary subjects. All groups were matched according to age, body mass index and nutritional status. Cutoff points to classify subjects with high plasma concentrations of Lp(a) and LDLc were 32 mg/dL and 128 mg/dL, respectively. For other variables the cutoff points were the third quartile values recorded in the control group, except for apo A-I and HDLc, for which we used the first quartile values. Persons who practice sports involving a high level of physical exertion (volleyball and soccer players) had a less favorable lipid profile compared to control subjects. In contrast, swimmers had a more favorable lipid profile. The odds ratio for lipid profile anomalies was significantly higher in volleyball and soccer players, and lower in swimmers. In the former two groups we observed a clear tendency toward simultaneous elevations in LDLc, apo B-100 and Lp(a). In contrast, the opposite interaction was seen in swimmers, who had lower values for all lipids. Our results show that stressful physical exertion can lead to abnormalities in plasma lipid profile.

Obesity and other risk factors for cardiovascular diseases among Africans: results from CARDIAC study in Tanzania

Objective: To investigate the prevalence of obesity and central adiposity and to assess if any significant relationship exists between obesity and other risk factors for cardiovascular diseases (CVD) in an African population. Methods: A cross-sectional, epidemiological study was conducted in three distinct areas: urban, rural and a pastoralist population in Tanzania. Results: The overall prevalence of obesity (body mass index (BMI)≥30 kg/m 2) was 14.2% and that of adiposity was 16.9%. Of the obese participants, 40.5% had reached higher education levels and 59.1% lived in the urban area. Significant hypertension (48.1%), hypercholesterolemia (32.4%), hypertriglyceridemia (20.3%), elevated LDL-C (33.8%), and hyperglycemia (4.6%) were seen among obese participants. Elevated plasma leptin concentration and low REE were observed among obese participants. Conclusion: Obesity, associated with significant biochemical derangement, is now a health problem in Tanzania. Effective strategies for primary prevention of obesity need to be introduced, especially in urban areas in Tanzania.

Clinical and biochemical characterisation of patients with autosomal recessive hypercholesterolemia (ARH)

Background and Aim: Inherited hypercholesterolemias are common disorders characterised by elevated LDL-C levels and premature coronary heart disease. We have recently described a recessive form of hypercholesterolemia (autosomal recessive hypercholesterolemia, ARH) in which LDL catabolism is reduced because of a mutation in the gene coding for an adaptor protein that impairs LDL-receptor (LDL-R) activity in the liver. The aim of this study was to characterise in detail the phenotypes of subjects with homozygous and heterozygous ARH. Methods and Results: We have so far identified six Italian families with ARH and studied the clinical and biochemical characteristics of 11 homozygotes (age 13–47 years) and 12 obligate heterozygotes (age 42–83 years). The study protocol included an evaluation of the lipoprotein profile, LDL-R activity in fibroblasts, LDL binding activity, and apo E genotype; a structured questionnaire (CHD risk factors, medical history, current medications); a physical examination, resting and stress ECG, ultrasound examinations (heart, carotid arteries, Achilles tendons) and coronary angiography. The pedigrees were characterised by the absence of vertical transmission; consanguinity was documented in two families. Only the two previously described Sardinian mutations, ARH1 (c.432insA) and ARH2 (c.65 G>A), were identified in the probands. All of the ARH homozygotes had large tendinous xanthomas, two had exertional angina, and four a positive stress ECG. None had experienced myocardial infarction or stroke. More than half had instrumental signs of atherosclerosis such as a positive stress ECG or positive carotid echo-doppler examination. The ARH heterozygotes were consistently normal and had a normal lipid profile. Conclusions: The ARH phenotype resembles that of familial hypercholesterolemia (FH) homozygotes, but ARH may be a less serious illness. The absence of vertical transmission, and the presence of mild coronary heart disease and consanguinity, can suggest a possible diagnosis of ARH. ARH might be considered a phenocopy of FH but heterozygous subjects seem to have a consistently normal phenotype.

Significance of triglycerides for other metabolic parameters in the familial metabolic syndrome

The relationship between the various degrees of glucose tolerance and metabolic parameters have already been examined in various studies. Whether and to what extent the triglycerides (TG) affect other metabolic parameters in the different degrees of glucose tolerance is not certain. We therefore studied the importance of the triglycerides within a defined glycemic state in patients with an elevated familial risk for metabolic diseases. We examined 866 patients (380 men, 486 women, mean age 44,4 years) in the "Familial Metabolic Syndrome Study" (FAMES). The patients were assigned to various degrees of glucose tolerance, according to the result of an oral glucose tolerance test. All degrees were divided into subgroups in respect of the triglyceride level (TG < 1,7 or TG >/= 1,7 mmol/l). In these subgroups we measured various metabolic parameters like fasting glucose, insulin resistance, insulin and proinsulin levels, HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), uric acid, HbA (1c), and free fatty acids (FFA). In patients with normal glucose tolerance the hypertriglyceridemia is already associated with other components of the metabolic syndrome like elevated HbA (1c), free fatty acids, proinsulin and insulin levels, worsened insulin sensitivity, elevated uric acid and LDL-C levels as well as a lowered HDL-C level. The patients with diabetes and hypertriglyceridemia also showed higher levels of FFA, proinsulin and insulin, a lower HDL-C level and a more prominent insulin resistance. Hypertriglyceridemia is an indicator for insulin resistance and elevated levels of other components of the metabolic syndrome within the various degrees of glucose tolerance.

Prevalence of dyslipidemia and risk factors in Campos dos Goytacazes, in the Brazilian state of Rio de Janeiro.

To determine the prevalence of dyslipidemias in adults in the city of Campos dos Goytacazes, in the Brazilian state of Rio de Janeiro, and to identify its relation to risk factors. Cross-sectional, population-based, observational study with sampling through conglomerates and stratified according to socioeconomic levels, sex, and age, with 1,039 individuals. Risk factors, familial history, blood pressure, anthropometric measurements, glucose, triglycerides and cholesterol were determined. The following prevalences were observed: of dyslipidemias 24.2%; of hypercholesterolemia, 4.2%; of elevated LDL-C, 3.5%; of low HDL-C, 18.3%; and of hypertriglyceridemia, 17.1%. The following mean levels were observed: cholesterol, 187.6 +/- 33.7 mg/dL; LDL-C, 108.7 +/- 26.8 mg/dL; HDL-C, 48.5 +/- 7.7 mg/dL; and triglycerides, 150.1 +/- 109.8 mg/dL. The following variables showed a positive correlation with dyslipidemia: increased age (P<0.001), male sex (P<0.001), low familial income (P<0.001), familial history (P<0.01), overweight/obesity (P<0.001), waist measure (P<0.001), high blood pressure (P<0.001), and diabetes mellitus (P<0.001). The following variables had no influence on dyslipidemias: ethnicity, educational level, smoking habits, and sedentary lifestyle. The frequency of lipid changes in the population studied was high, suggesting that measures for the early diagnosis should be taken, in association with implementation of programs for primary and secondary prevention of atherosclerosis.

A longitudinal evaluation of the NCEP-Peds guidelines for elevated total and LDL cholesterol in adolescent girls and boys

The National Cholesterol Education Program-Peds (NCEP-Peds) guidelines established single sets of cutoffs for evaluating borderline and elevated total (TC) and low density lipoprotein (LDL-C) cholesterol in children up to age 19 years, corresponding roughly to the 75th and 95th percentiles, respectively, of these distributions in the Lipid Research Clinics Prevalence Study (1972–1976). These cutoffs do not take into account the effects of puberty on these lipids. The purpose of this review is to describe adolescent changes and to demonstrate the effects of these changes on the prevalence of elevated TC and LDL-C. Thus, we present data on changes in growth velocity, obesity, fat patterning and pubertal maturation and apply the NCEP-Peds cutoffs to biracial adolescent cohorts by single year of age to show the variability in the percentage of children identified for follow-up. The net effect of these adolescent changes is a fall in the percentage of children identified for follow up of almost 50% from age 10 to mid-adolescence, followed by a rise in the percentages. Using multivariable analyses, we show that increasing obesity (body mass index, kg/m 2) increases the prevalence of dyslipidemias and advancing puberty decreases it. Thus, how a child is diagnosed may be a function of age and pubertal status at the time of the tests. These results suggest a need to modify the NCEP-Peds classification cutoffs to account for pubertal status.

Monogenic hypercholesterolemia: new insights in pathogenesis and treatment.

Monogenic hypercholesterolemia: new insights in pathogenesis and treatment.

Protective Effect of the Immunosuppressant Sirolimus Against Aortic Atherosclerosis In Apo E-Deficient Mice

Atherosclerosis is a chronic inflammatory disease that develops in response to injury to the vessel wall, and is augmented by hypercholesterolemia. To further delineate the role of the immune system and local factors in this process, we assessed the effects of the immunosuppressant sirolimus (Rapamycin, RAPAMUNE, Wyeth, Collegeville, PA) on atherosclerosis in the apoE-deficient (apoE KO) mouse, a well-accepted model of cardiovascular disease. ApoE KO mice were fed a high fat diet and sirolimus was administered. After 12 weeks, atherosclerotic lesions and plasma lipoproteins were measured. The expression of cytokines associated with atherosclerosis was also examined. All groups demonstrated plasma total cholesterol (TC) >1100 mg/dL. Sirolimus treatment was associated with a 30% increase in LDL-cholesterol (LDLc) and a dose-dependent elevation in HDL-cholesterol (HDLc). Despite increased LDLc, aortic atherosclerosis was markedly reduced in all sirolimus-treated groups. Sirolimus treatment resulted in decreased expression of IL-12p40, IFN-gamma and IL-10 mRNA. In contrast, TGF-beta1 was elevated. Sirolimus significantly reduced atherosclerosis in apo E-KO mice; this effect is independent of, and obviates, elevated plasma TC and LDLc. Sirolimus might therefore be of benefit on atherosclerosis in patients undergoing therapy, independent of any impact on circulating lipids.

COMMON GENETIC POLYMORPHISMS AND CHOLESTEROL RESPONSE TO EXERCISE TRAINING

Common genetic polymorphisms may affect exercise training induced improvements in plasma low-density lipoprotein (LDL-C) and total cholesterol (TC) levels. PURPOSE Major risk factors for cardiovascular disease include elevated TC and LDL-C. Exercise training is known to affect these risk factors to varying degrees among individuals. The purpose of this study is to identify genetic factors that affect the exercise training response. METHODS Subjects were 90 nonsmoking sedentary males and post-menopausal females aged 50–75 years. Subjects underwent 6 months of supervised aerobic exercise training after a six-week dietary stabilization period. Changes in LDL-C and TC were statistically analyzed using a modified backward elimination multiple regression technique. Genes investigated included those coding for apolipoprotein E (Apo E), lipoprotein lipase Pvu II (LPL-Pvu II), lipoprotein lipase Hind III (LPL-Hind III), cholesterol ester transfer protein (CETP), hepatic lipase (HL), endothelial lipase (LIPG), fatty acid binding protein-2 (FABP-2), and interleukin-6 (IL-6). Genotypes were determined using standard techniques. RESULTS No single gene or gene-gene interactions were found to significantly contribute to changes in TC with exercise training. A single gene (LPL-Pvu II) along with gene-gene interactions (LPL-Pvu II*CETP and CETP*FABP-2) were found to explain 4.9%, 9.8%, and 7.4% of the variance in LDL-C response to exercise training respectively. CONCLUSION Genetic variation partially explains the variation in LDL-C response to exercise training. Further investigation including additional subjects and analysis of other genetic polymorphisms may further explain this variance.

Pre-Menopausal Women, Classified as Hypo- or Hyper-Responders, do not Alter their LDL/HDL Ratio Following a High Dietary Cholesterol Challenge

Background: Cholesterol is the dietary component that has elicited the most public interest in conjunction with coronary heart disease. However, the impact of excess dietary cholesterol intake on plasma cholesterol levels cannot be accurately predicted; therefore, its role in disease progression is not straightforward. Individual response variation can be due to factors such as ethnicity, hormonal status, obesity and genetic predisposition.Objective: The purpose of this study was to evaluate the differences that occur within the plasma compartment of normolipidemic pre-menopausal women, classified based on their response to a high dietary cholesterol challenge.Design: We recruited 51 pre-menopausal women (29 Caucasian and 22 of Hispanic origin) aged 18 to 49 years with initial plasma cholesterol concentrations ranging from 3.62 to 5.17 mmol/L. Using a cross-over research design, women were randomly allocated to an egg (640 mg additional dietary cholesterol per day) or placebo group (0 mg additional dietary cholesterol per day) initially, and the two 30 day periods were separated by a three-week washout.Results: An initial evaluation of the ethnicity effects revealed elevations in both plasma LDL-C (p < 0.0001) and HDL-C (p < 0.001) concentrations in both Hispanics and Caucasians during the high dietary cholesterol period. However, these increases were not accompanied by a change in the LDL/HDL ratio. Subjects were then classified as hypo- (< 0.05 mmol/L increase in total plasma cholesterol per each additional 100 mg of dietary cholesterol consumed per day) or hyper-responders (≥0.06 mmol/L increase in total blood cholesterol per each additional 100 mg of dietary cholesterol consumed per day), based on their reaction to the additional dietary cholesterol provided. Hypo-responders did not experience an increase in LDL-C or HDL-C during the egg period, while both lipoproteins were elevated in hyper-responders. However, the LDL/HDL ratio, an important parameter of coronary heart disease risk, was maintained for all subjects during the egg period independent of response. Furthermore, hyper-responders had higher concentrations of apo C-III (p < 0.001), apo B (p < 0.001) and cholesterol ester transfer protein (CETP) (p < 0.05) during this period.Conclusion: These data revealed that excess dietary cholesterol does not increase the risk of developing an atherogenic lipoprotein profile in pre-menopausal women, regardless of their response classification. Although the addition of 640 mg of cholesterol to the diet did result in an increase in plasma cholesterol in hyper-responders, the LDL/HDL ratio was maintained. This result, accompanied by increases in CETP activity, leads to the speculation that hyper-responders may process the excess cholesterol in the plasma compartment through an enhancement of the reverse cholesterol transport pathway. With this mechanism identified, further measurement of additional parameters is needed to verify this conclusion.

Identification of recurrent and novel mutations in the LDL receptor gene in German patients with familial hypercholesterolemia.

In order to identify mutations in the low density lipoprotein receptor (LDLR) gene in primary hypercholesterolemia, we screened 100 unrelated German individuals with elevated plasma LDL-C (LDL-C > 4,7 mmol/l) for mutations in the 18 exons and their flanking intronic sequences including the promoter region of the LDL-R gene using a combination of polymerase chain reaction (PCR), denaturing gradient gel electrophoresis (DGGE) and direct sequencing. In addition we tested all patients for the presence of mutations in codons 3456 - 3553 of the gene encoding apolipoprotein B-100. In 56 individuals we detected 37 different mutations affecting the LDL-R gene, 16 of which, designated C122R, C127Y, C163W, F179L, R236W, E296X, R553C, V618D, T721I, V785D, G1358+2A, 257delTCTGGAGGT, 657delC, 676insACGGTATGGACTGCAdelGACG, C1205delTCT, 2420delTCCTTCT, have not yet been reported. One proband was a compound heterozygote showing two separate sequence variations (E207X and T705I). Seven patients were heterozygous for the mutation R3500Q within the apoB-100 gene. These results demonstrate that there is a broad spectrum of mutations in the LDL-R gene and that the R3500Q mutation is a frequent cause of hypercholesterolemia in the German population.

Relationships between body weight change and cardiovascular disease risk factors in male former athletes

To evaluate the cardiovascular disease risk factor profile in former athletes according to their weight-change patterns during the postcompetitive period. Cohort study with a retrospective assessment of baseline weight of male former top-level athletes. One-hundred and fifty top-level athletes aged 35-60 y were divided into four groups according to the weight-change patterns during the postcompetitive period (weight loss, constant weight, weight gain over 3.0 kg and weight gain over 10.0 kg). Anthropometric measurements (height, weight, BMI, percentage fat, skinfolds, waist-to-hip-ratio (WHR), resting systolic and diastolic blood pressure (SBP, DBP), serum lipids and lipoproteins (CHOL, HDL-C, LDL-C, TG), and physical working capacity. A questionnaire was drawn up to evaluate current and previous physical activity, lifestyle indices and to record weight at the age of 20 (according to sports diaries). Weight gain over 10.0 kg in former athletes was closely associated with higher body mass index, percentage body fat, skinfold thickness, WHR, SBP, DBP, LDL-C and TG values, as well as lower HDL-C, HDL-C/CHOL ratio and physical working capacity values. After adjustment for confounders, the weight gainers over 10.0 kg revealed a higher risk of hypertension (OR 6.65; 95% CI 2.99-11.65), abdominal fat distribution pattern (OR 10.51; 95% CI 6.11-16.24), elevated LDL-C (OR 1.88; 95% CI 1.15-3.06) and hypertriglyceridemia (OR 3.52; 95% CI 1.12-8.56) compared with those whose weight was constant. Weight loss and weight gain less than 10.0 kg were significantly related to increased risk for abdominal fat distribution pattern. The results of the present study showed that weight gain during the postcompetitive period was associated with a higher prevalence of cardiovascular disease risk factors in male former athletes.

Apo E Effects on Blood Cholesterol Are Independent of Growth and Maturation in Adolescent Girls: Project HeartBeat!

P15 Apolipoprotein E polymorphism (apo E) is a genetic determinant of lipid and lipoprotein levels and subsequent risk for CHD. We have previously demonstrated that girls with ε3/3 or ε3/4 genotypes had both higher total (TC) and LDL-cholesterol (LDL-C) throughout ages 8 to 18 compared with those with the ε2/3 genotype. The current analysis further explored potential confounding or interaction effects of physical growth, body composition, sexual maturation, and endocrine function with apo E. In Project HeartBeat!, a mixed longitudinal study of CVD risk factor development in children, apo E genotyping was performed among 331 girls aged 8, 11, and 14 years at baseline. Plasma lipid concentrations, weight, height, body mass index (BMI), skinfolds, fat free mass (FFM), percent body fat (%BF), Tanner stage (pubic hair, PH), and endocrine function (estradiol, EST) were determined by standard methods 3 times a year for up to 4 years. Analyses were restricted to 247 Caucasian girls. The numbers of measurements used ranged from 1090 to 1960 according to the combination of variables in different multilevel linear models. FFM, BMI, %BF, PH, and EST each showed a significant effect on TC and LDL-C whether tested alone or included in models containing age (age, age 2 , and age 3 ), apo E (ε2/3, ε3/3, and ε3/4), and age-apo E interaction terms. Age, apo E, and age-apo E interaction terms were strong, independent determinants of TC and LDL-C. Except for a ε3/4-by-%BF interaction, all 2-way interaction effects between apo E and FFM, BMI, %BF, PH, and EST were not significant in either TC or LDL-C models (P&gt;.05). We conclude that the apo E effects on age-related serial changes in TC and LDL-C are independent of physical growth, body composition, sexual maturation, and estradiol level in normal adolescent girls. Girls with ε3/3 or ε3/4 genotypes may be at higher risk for elevated TC and LDL-C later in life. These genotypes were found in 85% of the study population and may be important to identify in intervention studies or in clinical practice to evaluate responsiveness to lipid-lowering therapy.

Role of lipids, lipoproteins and vitamins in women with breast cancer

Objectives: Improper balance between the production of reactive oxygen metabolites (ROMs), and antioxidative defense system have been defined as oxidative stress in various pathologic conditions. Lipids, lipoproteins and antioxidative vitamins have been associated with the risk of breast cancer. The present case-control study was conducted to investigate the status of antioxidative vitamins (A, C and E), lipids (total cholesterol; TC and triglycerides; TG), lipoproteins (high-density lipoprotein cholesterol; HDL-C and low-density lipoprotein cholesterol; LDL-C) and retinol-binding protein (RBP) in breast cancer patients. The aim of the study was to find out oxidative stress in breast cancer. Design and methods: Plasma lipids, lipoproteins and vitamins were estimated in 54 untreated breast cancer patients of different clinical stages and in 42 age- and sex-matched controls. Results: Plasma TC ( p < 0.05), and LDL-C and TG ( p < 0.01) were found to be significantly elevated among breast cancer patients as compared to the controls. On the other hand, plasma HDL-C concentration ( p < 0.001) and vitamin C and E ( p < 0.01) were observed significantly decreased in breast cancer patients than in the controls. The maximum changes in plasma TC, and vitamin C and E concentrations were observed in breast cancer patients with stage IV when compared with controls. Conclusion: The study suggests that higher levels of TC and TG may play important role in carcinogenesis. Furthermore, the elevated plasma LDL-C concentration, which is more susceptible to oxidation, may result in higher lipid peroxidation in breast cancer patients. However, decreased concentrations of HDL-C and vitamin C and E are not likely to be sufficient enough to counter higher ROMs production reported earlier in breast cancer patients that may cause oxidative stress leading to cellular and molecular damage thereby resulting in cell proliferation and malignant conversions.

Physical activity for preventing and treating obesity-related dyslipoproteinemias.

The clinical trial data were reviewed on effects of physical activity on obesity-related dyslipoproteinemias (specifically low HDL-cholesterol (HDL-C), elevated triglycerides (TG), and high total and LDL-cholesterol (TC and LDL-C)) in adult men and women. Effort was made to identify all randomized clinical trials (RCT), with exercise intervention programs of at least 4 months' duration, which had lipoprotein outcomes. Those that had both an exercise only intervention and control groups or both a diet plus exercise and identical diet only intervention groups were reviewed. Tables were developed of baseline characteristics and weight and lipoprotein changes for aerobic exercise trials by body mass index: 1) < 25.0 kg x m(-2), 2) 25.0-29.9 kg x m(2), and 3) > or = 30.0 kg x m(-2)and for studies involving resistance exercise or increased energy expenditure from daily activities versus structured exercise programs. Very few RCT were found that specifically addressed the role of physical activity in preventing or treating obesity-related adverse lipoprotein levels. There was essentially no evidence found in lean or overweight men or women to support a specific role for exercise in improving undesirable lipoprotein levels; however, trial data strongly suggest that the addition of exercise to a hypocaloric, reduced-fat diet improves HDL-C and TG in men and women with generally desirable initial levels and reduces LDL-C in men and women with initially elevated LDL-C levels. The evidence is also reasonably strong that weight loss, including that achieved solely by exercise, improves HDL-C and TG in obese men, without reducing LDL-C, whereas it remains weak for women. There are also virtually no trial data to support a role for resistance exercise or an increase in daily living activities for improving obesity-related lipoproteins. Current evidence from RCT is too limited to determine whether physical activity can raise low HDL-C or lower high TG or LDL-C levels in overweight and obese individuals.

Risk factors for atherosclerosis in students of a private university in São Paulo-Brazil.

To characterize the risk profile for atherosclerosis (AS) in adolescents and young adults of a private university in São Paulo. Clinical, nutritional, and laboratory parameters were evaluated in 209 students of both genders aged 17 to 25 years. In addition to determination of the lipid profile, the association of its abnormal values with other risk factors for AS was also investigated. Increased levels of total cholesterol, LDL-C and triglycerides (TG) were observed in 9.1%, 7.6% and 16.3% of the students, respectively, and decreased levels of HDL-C in 8.6% of them. Prevalence of the remaining risk factors analyzed was elevated: sedentary life style (78.9%); high intake of total fat (77.5%); high cholesterol intake (35.9%); smoking, hypertension (15.8%) and obesity (7.2%). There was an association between elevated LDL-C and TG levels and sedentary life style and body mass index. The high prevalence of risk factors for AS in young individuals draws attention to the need for adopting preventive plans.

A PRELIMINARY STUDY OF CARDIOVASCULAR RISK BEHAVIORS IN ADOLESCENT TRANSPLANT PATIENTS

690 After transplantation, many adolescents experience significant weight gain coupled with poor physical activity. These changes are generally believed to be related to the improved feeling of well being, increased appetite, and altered metabolism associated with immunosuppressive drugs and transplantation. Since renal transplant recipients' life expectancies are increasing, long term risk factors for cardiovascular disease must be addressed. To deter risk factors and help encourage compliance, an educational program including diet, medication, and risk behaviors was instituted at the time of transplantation and twice yearly thereafter. The primary purpose of this study was to determine the effectiveness of the current education program. Patients (24) receiving care at the University of Alabama at Birmingham were enrolled: median 17 months post-transplant (range 1-152), 75% male/25% female, 58% white/42% black, median age 17 years (range 13-23). Anthropo-metric data demonstrated 67% of subjects with moderate to severe growth retardation, 72% were overweight to morbidly obese (based on percent ideal body weight and body mass index), triceps skinfolds showed that 82% were obese with mildly to severely increased fat stores, mid-arm muscle circumferences indicated that 88% had mild to severe muscle wasting and protein depletion. Other data related to cardiovascular risk factors (blood pressure, lipid levels) were evaluated: 86% of subjects had significantly elevated BP, 50% had elevated cholesterol, 40% had elevated triglycerides, and 40% had elevated LDL-C and VLDL-C. Significant correlations were noted between cyclosporine levels and total cholesterol and LDL-C. To determine patient behaviors, subjects completed the Youth Risk Behavior Survey and were found to be significantly less physically active than the reference YRBSS students. To determine dietary intake, subjects completed a 3 day diet diary and 24 hour diet recall. In spite of diet education, 28% of the subjects responded that they were on no special diet, and only 5.6% described the prescribed diet regimen. Though approximately 72% were considered to be obese, 78% were below Recommended Dietary Allowances for calories. This suggests the diet records were not reliable predictors of actual intake. These data suggest that the majority of these patients are obese with a high percentage of their body composition as fat, have significantly elevated lipid levels, poorly controlled hypertension, and decreased physical activity. All of these have been demonstrated to increase their risk for cardiovascular disease. Clearly new approaches to patient care and education are needed.

Association of plasma triglyceride-rich lipoprotein remnants with coronary atherosclerosis in cases of sudden cardiac death

Among the risk factors for coronary atherosclerosis, elevated LDL-C level is best known. The action of lipoprotein lipase on triglyceride-rich lipoproteins produces remnant lipoprotein particles enriched in cholesterol and apolipoprotein E (apo E). Apo E serves as the ligand for uptake of remnant lipoproteins via the LDL-receptor or the remnant receptor. In this study, postmortem plasma total cholesterol, triglycerides (TG), VLDL-C, HDL-C, lipoprotein (a) [Lp(a)] and remnant-like lipoprotein particles (RLP)-cholesterol, RLP-TG, apolipoproteins B, C III and E were measured, together with LDL-C to assess their potential contribution to the severity of coronary and aortic atherosclerosis of the 197 cases of sudden death (132 cardiac death and 65 non-cardiac death). In all cases, the severity of coronary atherosclerosis was determined at postmortem pathological examination. RLP-cholesterol (RLP-C) and LDL-C concentrations were significantly higher in cases with advanced coronary atherosclerosis compared with those without coronary atherosclerosis; respective median values were 13.5 vs 8.4 mg/dl ( P<0.001) and 140 vs 115 mg/dl ( P<0.05). RLP-C levels were more strongly correlated with the severity score of coronary atherosclerosis than LDL-C.

DETECTION AND EVALUATION OF DYSLIPOPROTEINEMIA

The National Cholesterol Education Program Adult Treatment Panel II guidelines recommend that all adults 20 years of age and older undergo testing to detect dyslipoproteinemia. Clinical trials have proven conclusively that lowering levels of low-density lipoprotein (LDL) cholesterol reduces coronary heart disease (CHD) incidence and mortality and total mortality in patients with and without CHD. There is persuasive scientific evidence to include young adults, women, and the elderly in the recommendation for cholesterol management. In adult without CHD, testing can begin with measurement of total cholesterol (TC) and high-density lipoprotein (HDL) cholesterol in the nonfasting state, and the results can then be used to determine which individuals require a fasting lipoprotein analysis (total cholesterol, HDL, triglycerides, and estimation of LDL); patients with known CHD should begin with lipoprotein analysis. The level of LDL cholesterol and the presence or absence of other CHD risk factors determine the need for cholesterol-lowering therapy. Patients with known CHD are at highest risk for a CHD event and have the lowest LDL cholesterol goal (100 mg/dL); patients without CHD but with elevated LDL-C (130 mg/dL) and two or more other CHD risk factors are at high risk for developing CHD and have an LDL cholesterol goal of less than 130 mg/dL; patients free of CHD with high LDL cholesterol (160 mg/dL) but fewer than two other risk factors have a lower CHD risk and an LDL cholesterol goal of less than 160 mg/dL. Elevated triglyceride may be a marker for other factors that increase CHD risk. Raising HDL cholesterol, while not proven to be of benefit, is reasonable in patients at high CHD risk.

Low density lipoprotein receptor mutations in a selected population of individuals with moderate hypercholesterolemia

To evaluate mutations in the low density lipoprotein receptor (LDL-R) gene in moderate primary hypercholesterolemia, a combination of polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP) and direct sequencing, was used to screen the LDL-R gene in a selected population of 82 unrelated individuals with moderate elevation of plasma LDL-C [mean 4.55±0.55 mmol/l (176.4±21.6 mg/dl)]. Four subjects (5%) were found to be heterozygotes for missense mutations in the LDL-R gene. These mutations were located in four different exons (exons 6, 7 15 and 17) and all alters highly conserved residues of LDL-R protein. None of these mutations were detected in 79 normocholesterolemic individuals. The mutation in exon 15 (T705I) was previously reported in a compound heterozygote for familial hypercholesterolemia (FH). In the proband carrying the mutation in exon 17 (R793Q), an in vivo LDL turnover study was performed and it demonstrated a reduction of LDL catabolism. These findings demonstrate that mutations in the LDL-R may occur in primary moderate hypercholesterolemia. They also extend the concept that some FH patients may present with a mild phenotype.