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Biomedical subjects

Jiri Frohlich

Publications and source records attributed to Jiri Frohlich.

29 records · Page 2Linked to original sources
PubMed2003

Differential effects of simvastatin and atorvastatin on high-density lipoprotein cholesterol and apolipoprotein A-I are consistent across hypercholesterolemic patient subgroups.

BACKGROUND: In addition to lowering plasma levels of low-density lipoprotein cholesterol (LDL-C), statins also raise high-density lipoprotein cholesterol (HDL-C). HYPOTHESIS: Recent studies have shown that treatment with simvastatin results in larger increases in HDL-C than those seen with atorvastatin. The results of three clinical studies are analyzed, comparing the effects of simvastatin and atorvastatin on HDL-C and apolipoprotein A-I (apo A-I) in the total cohort and in several subgroups of hypercholesterolemic patients. The three studies were all multicenter, randomized clinical trials that included simvastatin (20-80 mg) and atorvastatin (10-80 mg) treatment arms. The subgroup analyses performed were gender; age (< 65 and > or = 65 years); baseline HDL-C (male: < 40 or > or = 40 mg/dl; female: < 45 or > or = 45 mg/dl), baseline LDL-C (< 160 or > or = 160 mg/dl), and baseline triglycerides (< 200 or > or = 200 mg/dl). RESULTS: Both drugs produced similar increases in HDL-C levels at low doses; however, at higher drug doses (40 and 80 mg), HDL-C showed a significantly greater increase with simvastatin than with atorvastatin (p < 0.05 to < 0.001). Therefore, while HDL-C remained consistently elevated across all doses of simvastatin, there appeared to be a pattern of decreasing HDL-C with an increasing dose of atorvastatin. A similar negative dose response pattern was also observed with apo A-I in atorvastatin-treated patients, suggesting a reduction in the number of circulating HDL particles at higher doses. Both drugs reduced LDL-C and triglycerides in a dose-dependent fashion, with atorvastatin showing slightly greater effects. The differential effects of atorvastatin and simvastatin on HDL-C and apo A-I were observed for both the whole study cohorts and all subgroups examined; thus, no consistent treatment-by-subgroup interactions were observed. CONCLUSION: The data presented show that, across different hypercholesterolemic patient subgroups, simvastatin increases HDL-C and apo A-I more than atorvastatin at higher doses, with evidence of a negative dose response effect on HDL-C and apo A-I with atorvastatin, but not simvastatin.

Apolipoprotein A-I↗
PubMed2003

Coronary atherosclerosis in anorexia nervosa.

BACKGROUND: Chest pain is a common complaint in patients with anorexia nervosa (AN). Of those who experience chest pain, about 20% meet the diagnostic criteria for typical or atypical angina. METHODS: We compared the intima-medial thickness (IMT) of the carotid artery measured by ultrasound in AN with controls and found no difference. RESULTS AND DISCUSSION: Although clinically relevant atherosclerosis can occur in patients with a normal IMT, there is a strong correlation between carotid IMT and coronary atherosclerosis. This suggests that an atherosclerotic origin of chest pain in AN patients is unlikely.

Adult↗
PubMed2003

Fractional esterification rate of cholesterol and ratio of triglycerides to HDL-cholesterol are powerful predictors of positive findings on coronary angiography.

BACKGROUND: We examined the predictive value of various clinical and biochemical markers for angiographically defined coronary artery disease (aCAD). Specifically, we assessed the value of the ratio of plasma triglyceride (TGs) to HDL-cholesterol (HDL-C) and the fractional esterification rate of cholesterol in plasma depleted of apolipoprotein B (apoB)-containing lipoproteins (FER(HDL)), a functional marker of HDL and LDL particle size. METHODS: Patients (788 men and 320 women) undergoing coronary angiography were classified into groups with positive [aCAD(+)] and negative [aCAD(-)] findings. Patient age, body mass index, waist circumference, blood pressure (BP), medications, drinking, smoking, exercise habits, and plasma total cholesterol (TC), LDL-cholesterol (LDL-C), HDL-unesterified cholesterol, HDL-C, TGs, FER(HDL), apoB, log(TG/HDL-C), and TC/HDL-C were assessed. Lipids and apoproteins were measured by standard laboratory procedures; FER(HDL) was determined by a radioassay. RESULTS: Members of the aCAD(+) group were older and had a higher incidence of smoking and diabetes than those in the aCAD(-) group. The aCAD(+) group also had higher TG, apoB, FER(HDL), and log(TG/HDL-C) and lower HDL-C values. aCAD(+) women had greater waist circumference and higher plasma TC and TC/HDL-C. aCAD(+) men, but not women, had higher plasma LDL-C. In the multivariate logistic model, the significant predictors of the presence of aCAD(+) were FER(HDL), age, smoking, and diabetes. If only laboratory tests were included in the multivariate logistic model, FER(HDL) appeared as the sole predictor of aCAD(+). Log(TG/HDL-C) was an independent predictor when FER(HDL) was omitted from multivariate analysis. CONCLUSIONS: FER(HDL) was the best laboratory predictor of the presence of coronary atherosclerotic lesions.

Adolescent↗
PubMed2003

Assessment of novel risk factors in patients at low risk for cardiovascular events based on Framingham risk stratification.

BACKGROUND: Coronary heart disease (CHD) risk assessed by the Framingham risk score does not take into account the various "novel" markers that are of increasing interest. In this paper we examine a low-risk population to determine which novel markers may be of additive value to the Framingham assessment of CHD risk. METHODS: Levels of high-sensitivity C-reactive protein (hs-CRP), soluble vascular cell adhesion molecule (s-VCAM), soluble intercellular adhesion molecule (s-ICAM-1), endothelial selectin (e-selectin), homocysteine and von Willebrand factor (vWF) were measured in 53 apparently healthy subjects recruited from a risk-reduction referral clinic. Carotid intima medial thickness (IMT) and number of plaques were determined by ultrasonography. Brachial ultrasound flow-mediated dilation (FMD) was also measured. Framingham risk scores were calculated and univariate and multivariate analyses of the resulting percent CHD risk over 10 years and novel markers were undertaken. RESULTS: Abnormal carotid IMT and presence of plaques, hs-CRP, homocysteine, FMD and s-ICAM-1 were detected with a high frequency in this low-risk cohort. Average IMT, number of plaques and homocysteine were highly correlated with the calculated percent CHD whereas measures of hs-CRP, s-ICAM-1 and FMD were independent of the percent CHD calculation. CONCLUSIONS: FMD, as a reflection of the functional status of the vasculature, and hs-CRP and s-ICAM-1, as indicators of inflammatory processes, were independent of Framingham risk assessment in patients at low risk for cardiovascular disease.

Adult↗
PubMed2002

Old and new risk factors for atherosclerosis and development of treatment recommendations.

1. The development of atherosclerosis, including the role of the classical and new risk factors, is briefly reviewed an emphasis on the links between some of these risk factors and atherogenesis. 2. While genetic factors are doubtlessly important, they contribute (from the population point of view) little to the overall burden of atherosclerosis. 3. Our studies on the relationship between abdominal obesity and metabolic risk factors in two ethnic groups, namely individuals of Cantonese and European background, suggest that different ranges for at least some of the risk factors should be established for specific ethnic groups (e.g. waist circumference for individuals of Chinese and European background). 4. Using the example of differences between Cantonese heterozygotes for familial hypercholesterolaemia living in Vancouver, Canada, and Canton, China, we demonstrate how the environment can modify a genetic predisposition for atherosclerosis. 5. Gender differences are illustrated by a study of serum lipoprotein (a) as a risk factor in men and women. 6. The principles of current Canadian recommendations for the assessment and treatment of atherosclerosis are outlined; they are based on knowledge gained from both basic and clinical research of atherosclerosis.

Arteriosclerosis↗
PubMed2002

Hypertriglyceridemic hyperapoB in type 2 diabetes.

OBJECTIVES: Much less attention has been paid to LDL in type 2 diabetes than to VLDL or HDL. In particular, there are few data on apoB levels in these patients. Moreover, most reports have focused on mean lipoprotein levels and consequently there is little information on the frequencies of the various dyslipidemic phenotypes. RESEARCH DESIGN AND METHODS: Plasma and lipoprotein lipids, apoB and apoA1 were measured by standardized methods. LDL particle size was determined by PAGE. The total cohort was divided into phenotypes by two different methods. The first was based on triglycerides (> or = or <1.5 mmol/l) and LDL cholesterol (> or = or <4 mmol/l), whereas the second was based on triglycerides (> or = or <1.5 mmol/l) and apoB (> or = or <120 mg/dl). RESULTS: For the overall cohort, plasma triglycerides were elevated (2.13 +/- 1.6 mmol/l), total and LDL cholesterol were normal (5.34 +/- 1.1 and 3.28 +/- 0.88 mmol/l, respectively), and peak LDL size was reduced (252.9 +/- 5.8 A). HDL cholesterol was between the 25th and 50th percentiles of the general population (1.12 +/- 0.36 mmol/l). The average level of apoB was 114 +/- 29 mg/dl, a value that is between the 50th and 75th percentiles of the general population and is higher than that for LDL cholesterol, which was between the 25th and the 50th percentiles of the population. The results of the phenotyping analysis were as follows. Using the conventional approach, only 23% has abnormal LDL, i.e., an elevated LDL cholesterol level. Using the new approach, almost 40% has an elevated apoB and therefore an elevated LDL particle number. Only 12.8% has combined hyperlipidemia based on the conventional approach, whereas almost one-third had the equivalent, hypertriglyceridemic hyperapoB-based on the new algorithm. The severity of the dyslipoproteinemia in this group was noteworthy. Although the average LDL cholesterol was 3.91 mmol/l, a value just below the 75th percentile of the general population, the average apoB was 145 mg/dl, a value that approximates the 95th percentile of the population. CONCLUSIONS: The dyslipidemic profile of patients with type 2 diabetes is not uniform. A substantial group have normal lipids and normal LDL particle number and size whereas others have markedly abnormal profiles. Diagnosis based on triglycerides and apoB rather than triglycerides and LDL cholesterol revealed that more than one in five had hypertriglyceridemic hyperapoB, which is characterized by hypertriglyceridemia, marked elevation of LDL particle number, small dense LDL, and low HDL, a constellation of abnormalities that is associated with markedly accelerated atherogenesis and therefore justifies intensive medical therapy.

Apolipoproteins↗
PubMed2002

Can measurement of serum apolipoprotein B replace the lipid profile monitoring of patients with lipoprotein disorders?

BACKGROUND: Current clinical guidelines require that five indices (total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, and the total/HDL cholesterol ratio) be measured or calculated to assess the lipid-related risk of vascular disease. All five are also targets of therapy and therefore all must be measured initially and at follow-up. Considerable evidence indicates that apolipoprotein B (apo B) is a better index of reaching or not reaching treatment targets than total or LDL cholesterol. METHODS: The objective of this study was to examine whether measurement of a single marker (apo B) led to the same categorization of risk as the traditional five indices (lipid profile). If both apo B and lipid profile indicated that the patient was either within or outside their respective treatment targets, the indices were considered concordant. If not, the indices were considered discordant. Concordance/discordance was examined in 215 patients at their first and last clinic visit. RESULTS: Concordance was high in both higher (88% at the first and 92% at the last clinic visit) and lower (76% at the first and 78% at the last clinic visit) risk groups at both the initial and final visits. Discordance was virtually restricted to the group with hypertriglyceridemia with normal concentrations of apo B, a group in which little independent evidence points to any substantially increased risk of vascular disease. CONCLUSIONS: These data raise the possibility that at least for high risk patients treated with statins, follow-up could be simplified and expenses reduced if only apo B were measured. They also raise the possibility that outcome might be improved if the therapeutic algorithm were simplified.

Apolipoproteins B↗
PubMed2002

Efficacy of a Therapeutic Lifestyle Change/Step 2 diet in moderately hypercholesterolemic middle-aged and elderly female and male subjects.

Lifestyle modification to decrease cardiovascular disease (CVD) risk has recently been reaffirmed by both the National Cholesterol Education Program and American Heart Association (AHA). Using a randomized crossover design, the Therapeutic Lifestyle Change (TLC)/Step 2 diet relative to a typical Western diet was assessed in 36 moderately hypercholesterolemic subjects in a clinical setting under isoweight conditions. Mean lipoprotein and apolipoprotein levels (fasting and non-fasting), fatty acid profiles, parameters of HDL metabolism, and glucose homeostasis were determined. Relative to the Western diet, the TLC/Step 2 diet resulted in 11% and 7% lower LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C), respectively, with no significant change in TG levels or total cholesterol-HDL-C ratio. Similar responses were observed in the non-fasting state. Linoleic (18:2n-6c) and alpha-linolenic (18:3n-3) acids increased at the expense of oleic acid (18:1n-9c) in the cholesteryl ester, TG, and phospholipid subfractions. The dietary changes had no significant effect on fractional esterification rate of HDL, phospholipid transfer protein (PLTP), or cholesterol ester transfer protein activities, or glucose and insulin levels. Female and male subjects responded similarly. The TLC/Step 2 diet resulted in a decrease in some CVD risk factors and no apparent adverse effects in others.

Aged↗
PubMedDate not supplied

Dietary measures and exercise training contribute to improvement of endothelial function and atherosclerosis even in patients given intensive pharmacologic therapy.

PURPOSE: Atherosclerosis contributes to cardiovascular mortality and morbidity even with aggressive lipid management. Our objective is to determine whether a combined pharmacological and lifestyle intervention can improve atherosclerosis. METHODS: We conducted a 2-year observational study at a specialized clinic in a tertiary care hospital. One hundred fifty-six subjects with coronary disease were enrolled in an intensive pharmacological management and lifestyle measures (including counseling and exercise training) program designed to reach specific targets. The main outcome measures were carotid intima media thickness and plaque area; brachial artery flow-mediated dilation; nitroglycerin-mediated dilation; flow-mediated dilation-nitroglycerin-mediated dilation ratio; laboratory parameters including lipids, glucose, creatinine, and homocysteine; and physical fitness. RESULTS: At completion, there were improvements in lipids and physical fitness. There were no overall changes in flow-mediated dilation, nitroglycerin-mediated dilation, or carotid intima media thickness in the entire cohort. However, multivariate logistic regression showed that dietary and exercise variables, such as increasing fiber intake and reducing body weight and body fat percentage, were independent predictors of improvements in endothelial function and carotid plaque burden. CONCLUSIONS: Even in the setting of intensive pharmacological therapy, lifestyle interventions, including exercise training and dietary changes, are important determinants of improved endothelial function and atherosclerosis.

Analysis of Variance↗