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Biomedical subjects

Jiri Frohlich

Publications and source records attributed to Jiri Frohlich.

At least 19 recordsLinked to original sources
PubMed2006

Canadian Cardiovascular Society position statement--recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease.

Since the last publication of the recommendations for the management and treatment of dyslipidemia, new clinical trial data have emerged that support a more vigorous approach to lipid lowering in specific patient groups. The decision was made to update the lipid guidelines in collaboration with the Canadian Cardiovascular Society. A systematic electronic search of medical literature for original research consisting of blinded, randomized controlled trials was performed. Meta-analyses of studies of the efficacy and safety of lipid-lowering therapies, and of the predictive value of established and emerging risk factors were also reviewed. All recommendations are evidence-based, and have been reviewed in detail by primary and secondary review panels. Major changes include a lower low-density lipoprotein cholesterol (LDL-C) treatment target (lower than 2.0 mmol/L) for high-risk patients, a slightly higher intervention point for the initiation of drug therapy in most low-risk individuals (LDL-C of 5.0 mmol/L or a total cholesterol to high-density lipoprotein cholesterol ratio of 6.0) and recommendations regarding additional investigations of potential use in the further evaluation of coronary artery disease risk in subjects in the moderate-risk category.

Canada↗
PubMed2005

Lipoprotein(a) is an independent risk factor for cardiovascular disease in heterozygous familial hypercholesterolemia.

BACKGROUND: The role of lipoprotein(a) [Lp(a)] as a predictor of cardiovascular disease (CVD) in patients with heterozygous familial hypercholesterolemia (HFH) is unclear. We sought to examine the utility of this lipoprotein as a predictor of CVD outcomes in the HFH population at our lipid clinic. METHODS: This was a retrospective analysis of clinical and laboratory data from a large multiethnic cohort of HFH patients at a single, large lipid clinic in Vancouver, Canada. Three hundred and eighty-eight patients were diagnosed with possible, probable, or definite HFH by strict clinical diagnostic criteria. Multivariate Cox regression analysis was used to study the relationship between several established CVD risk factors, Lp(a), and the age of first hard CVD event. RESULTS: An Lp(a) concentration of 800 units/L (560 mg/L) or higher was a significant independent risk factor for CVD outcomes [hazard ratio (HR) = 2.59; 95% confidence interval (CI), 1.53-4.39; P < 0.001]. Other significant risk factors were male sex [HR = 3.19 (1.79-5.69); P < 0.001] and ratio of total to HDL-cholesterol [1.18 (1.07-1.30); P = 0.001]. A previous history of smoking or hypertension each produced HRs consistent with increased CVD risk [HR = 1.55 (0.92-2.61) and 1.57 (0.90-2.74), respectively], but neither reached statistical significance (both P = 0.10). LDL-cholesterol was not an independent predictor of CVD risk [HR = 0.85 (0.0.71-1.01); P = 0.07], nor was survival affected by the subcategory of HFH diagnosis (i.e., possible vs probable vs definite HFH). CONCLUSION: Lp(a) is an independent predictor of CVD risk in a multiethnic HFH population.

Adolescent↗
PubMed2005

Dietary sitostanol and campestanol: accumulation in the blood of humans with sitosterolemia and xanthomatosis and in rat tissues.

Dietary sitostanol has a hypocholesterolemic effect because it decreases the absorption of cholesterol. However, its effects on the sitostanol concentrations in the blood and tissues are relatively unknown, especially in patients with sitosterolemia and xanthomatosis. These patients hyperabsorb all sterols and fail to excrete ingested sitosterol and other plant sterols as normal people do. The goal of the present study was to examine the absorbability of dietary sitostanol in humans and animals and its potential long-term effect. Two patients with sitosterolemia were fed the margarine Benecol (McNeill Nutritionals, Ft. Washington, PA), which is enriched in sitostanol and campestanol, for 7-18 wk. Their plasma cholesterol levels decreased from 180 to 167 mg/dL and 153 to 113 mg/dL, respectively. Campesterol and sitosterol also decreased. However, their plasma sitostanol levels increased from 1.6 to 10.1 mg/dL and from 2.8 to 7.9 mg/dL, respectively. Plasma campestanol also increased. After Benecol withdrawal, the decline in plasma of both sitostanol and campestanol was very sluggish. In an animal study, two groups of rats were fed high-cholesterol diets with and without sitostanol for 4 wk. As expected, plasma and liver cholesterol levels decreased 18 and 53%, respectively. The sitostanol in plasma increased fourfold, and sitostanol increased threefold in skeletal muscle and twofold in heart muscle. Campestanol also increased significantly in both plasma and tissues. Our data indicate that dietary sitostanol and campestanol are absorbed by patients with sitosterolemia and xanthomatosis and also by rats. The absorbed plant stanols were deposited in rat tissues. Once absorbed by sitosterolemic patients, the prolonged retention of sitostanol and campestanol in plasma might increase their atherogenic potential.

Adolescent↗
PubMed2005

Comparison of apolipoprotein B and plasma lipids as targets for lipid lowering treatment.

OBJECTIVE: To assess the discrepancies between LDL-cholesterol and apo B targets in patients at risk for vascular disease; namely, those with diabetes or hypertriglyceridemia and those with triglycerides <1.7 mmol/L and normal glucose homeostasis. METHODS: Lipid clinic patients were divided into two groups: Group 1 consisted of 182 patients whose triglyceride levels were >1.7 mmol/L or who had impaired fasting glucose or type 2 diabetes. In Group 2, there were 42 patients with triglycerides <1.7 mmol/L and normal glucose homeostasis. LDL-cholesterol and apo B were estimated during lipid clinic visits with patients on appropriate lipid lowering therapy. RESULTS: 46% of the patients in Group 1 who reached the high risk LDL-cholesterol target of <2.5 mmol/L did not reach apo B target of <0.9 g/L, while in Group 2, only 19% of those who reached the LDL-cholesterol target had apo B >0.9 g/L. CONCLUSION: Our findings demonstrate that a large percentage of patients with hypertriglyceridemia or impaired glucose tolerance, treated with lipid lowering agents, reach the LDL-cholesterol but not the apo B treatment targets.

Adult↗
PubMed2005

Differences in cardiovascular risks in the aboriginal and non-aboriginal people living in Bella Coola, British Columbia.

BACKGROUND: There is a lack of information regarding cardiovascular disease (CVD) in rural areas in British Columbia, Canada. To establish the relative prevalence of CVD risk factors in a rural area weanalyzed biochemical and clinical data collected on aboriginal and non-aboriginal descent people living in the community of Bella Coola. MATERIAL/METHODS: A retrospective review of the 2378 charts located in the Bella Coola Medical Clinic was done in the Fall of 2002. Anthropometric, biochemical and clinical information was obtained from 1,120 people of Nuxalk descent and 1258 people of mainly European descent. Children and adults of either sex, pre- and post-menopausal women, and patients with hyperlipidaemia, type 2 diabetes, and hypertension were included in the review. RESULTS: After adjusting for age, gender and BMI, non-aboriginal origin was associated with higher total and LDL-cholesterol (p<0.01) and aboriginal origin was associated with higher glucose levels (p < 0.0Ol). A significantly higher value for Log (TG/HDL), a plasma parameter defined as "Atherogenic index plasma (AIP)" was found in the aboriginal group. In addition, both aboriginal women and men had higher prevalence of metabolic syndrome than the non-aboriginal men and women. CONCLUSIONS: This study found different patterns of CVD risk factors i n non-aboriginal and aboriginalgroups living in the same geographic area. Based on the prevalence of metabolic syndrome, higher triglycerides and AIP, aboriginal participants, especially the women, are at a higher risk for CVD.

Adolescent↗
PubMed2005

Plant sterols and their role in combined use with statins for lipid lowering.

Cardiovascular disease (CVD) is currently one of the major contributors to the global burden of disease. Combination treatments to promote a maximal reduction of the ratio between total cholesterol and high-density lipoprotein are currently the most effective way of preventing CVD. In this review, we assess the role of plant sterols and statins in CVD prevention. Statins have been used by millions of patients at high to moderate risk of CVD, while plant sterols are potentially available to whole populations in food products. The benefits and risks of each compound, as well as the combination, are discussed.

Animals↗
PubMed2004

Phenotypic heterogeneity of sitosterolemia.

Sitosterolemia is a rare autosomal recessive disorder of lipoprotein metabolism characterized by xanthomas and increased plasma concentrations of plant sterols, such as sitosterol. Causative mutations occur in either the ABCG5 or ABCG8 gene, each of which encodes a sterol half-transporter expressed in the intestine. We report five Canadian subjects with nonsense mutations in these half-transporters: four related Caucasian subjects were homozygous for the ABCG8 S107X mutation, and one unrelated Japanese-Canadian subject was homozygous for a complex insertion/deletion (I/D) mutation in ABCG5 exon 3. A female subject with each mutation was symptomatic with coronary atherosclerosis: a 5-year-old ABCG8 S107X homozygote and a 75-year-old ABCG5 exon 3 I/D homozygote; these represent the extreme ends of the spectrum of vascular involvement in sitosterolemia. The largest reductions in plasma concentrations of sitosterol and LDL-cholesterol were seen with ezetimibe or bile acid sequestrant treatment, and less dramatic reductions were seen with statin drug treatment. These findings extend the range of clinical phenotypes in sitosterolemia caused by nonsense mutations in either ABCG5 or ABCG8.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed2004

Effect of fenofibrate-mediated increase in plasma homocysteine on the progression of coronary artery disease in type 2 diabetes mellitus.

The Diabetes Atherosclerosis Intervention Study (DAIS) examined the effects of fenofibrate or placebo on the progression of coronary artery disease (CAD) in 418 type 2 diabetic subjects with dyslipidemia. Fenofibrate use was associated with a 6% increase in high-density lipoprotein cholesterol, a 28% decrease in triglycerides, a 5% decrease in low-density lipoprotein cholesterol, and a 55% increase in plasma homocysteine (tHcy). The purpose of the present study was to determine whether this increase in tHcy in the fenofibrate group was associated with CAD progression or with clinical events. The increase in tHcy with fenofibrate (n = 207) was not related to changes in factors known to modulate tHcy levels (serum levels of Vitamin B(12), folate, or renal function). CAD was quantified by angiography at baseline and after a minimum of 3 years of therapy with fenofibrate or placebo. The primary end point was change in mean segment diameter (MSD), minimal lumen diameter, and percent stenosis. Baseline tHcy level was correlated with percent diameter stenosis (r = 0.111, p = 0.028). Baseline, but not end-of-study elevated tHcy levels, decreased the beneficial effect of fenofibrate. Unexpectedly, the final tHcy levels correlated negatively with CAD progression (r = -0.111, p = 0.031) in the overall group. In the fenofibrate group, there was no significant correlation between tHcy and minimal lumen diameter (r = -0.135, p = 0.069), or percent stenosis. An increase in tHcy levels was not correlated with adverse clinical events in the fenofibrate group. This analysis of the the DAIS reveals that the fenofibrate-mediated increase in tHcy levels does not attenuate the beneficial effects of fenofibrate on CAD progression or clinical events.

Aged↗
PubMed2004

Safety and tolerability of simvastatin plus niacin in patients with coronary artery disease and low high-density lipoprotein cholesterol (The HDL Atherosclerosis Treatment Study).

The high-density lipoprotein (HDL)-Atherosclerosis Treatment Study showed that simvastatin plus niacin (mean daily dose 13 mg and 2.4 g, respectively) halt angiographic atherosclerosis progression and reduce major clinical events by 60% in patients with coronary artery disease (CAD) who have low HDL, in comparison with placebos, over 3 years. How safe and well-tolerated is this combination? One hundred sixty patients with CAD, including 25 with diabetes mellitus, with mean low-density lipoprotein cholesterol of 128 mg/dl, HDL cholesterol of < or =35 mg/dl (mean 31), and mean triglycerides of 217 mg/dl were randomized to 4 factorial combinations of antioxidant vitamins or their placebos and simvastatin plus niacin or their placebos. Patients were examined monthly or bimonthly for 38 months; side effects (gastrointestinal upset, nausea, anorexia, vision, skin, and energy problems, or muscle aches) were directly queried and recorded. Aspartate aminotransferase, creatine phosphokinase (CPK), uric acid, homocysteine, and fasting glucose levels were regularly monitored. A safety monitor reviewed all side effects and adjusted drug dosages accordingly. Patients who received simvastatin plus niacin and those on placebo had similar frequencies of clinical or laboratory side effects: any degree of flushing (30% vs 23%, p = NS), symptoms of fatigue, nausea, and/or muscle aches (9% vs 5%, p = NS), aspartate aminotransferase (SGOT) > or =3 times upper limit of normal (3% vs 1%, p = NS), CPK > or =2 times upper limit of normal (3% vs 4%, p = NS), CPK > or =5 times upper limit of normal, new onset of uric acid > or =7.5 mg/dl (18% vs 15%, p = NS), and homocysteine > or =15 micromol/L (9% vs 4%, p = NS). Glycemic control among diabetics declined mildly in the simvastatin-niacin group but returned to pretreatment levels at 8 months and remained stable for rest of the study. This combination regimen was repeatedly described by 91% of treated patients and 86% of placebo subjects as "very easy" or "fairly easy" to take. Thus, the simvastatin plus niacin regimen is effective, safe, and well tolerated in patients with or without diabetes mellitus.

Blood Glucose↗
PubMed2004

Response to micronized fenofibrate treatment is associated with the peroxisome-proliferator-activated receptors alpha G/C intron7 polymorphism in subjects with type 2 diabetes.

OBJECTIVE: The association between polymorphisms in candidate genes related to lipoprotein metabolism and the reduction in plasma triglyceride (TG) in response to fenofibrate treatment was evaluated in subjects with type 2 diabetes treated with micronized fenofibrate (200 mg/day) for at least 3 years in the Diabetes Atherosclerosis Intervention Study. METHODS: The cholesteryl ester transfer protein Taq1B, LPL S447X, hepatic lipase -514 C-->T, peroxisome-proliferator-activated receptors alpha (PPARA) L162V and G/C intron 7 polymorphisms and the apolipoprotein E2/E3/E4 alleles were genotyped using PCR and restriction enzyme digestion. Subjects were divided into high TG-responders (with > 30% TG relative reduction after treatment) and low TG-responders. RESULTS: The frequency of the PPARA intron 7 G/G genotype was higher in high TG-responders than in low TG-responders (85% vs. 69%, P < 0.05). There was no significant difference between the percentage of high TG-responders and low TG-responders for any of the other genetic polymorphisms examined. In stepwise logistic regression, baseline TG and only the PPARA intron 7 polymorphism among the others were selected in the model as significant predictors of TG-response (odds ratio: 3.10, 95% CI: 1.28-7.52, P = 0.012 for PPARA polymorphism). With age, gender, body mass index, smoking status and HbA1c as additional factors, baseline TG (P< 0.0001), intron 7 (P = 0.013), body mass index (P = 0.040) and LPL-S447X (P = 0.084) were significant predictors of TG-response. CONCLUSION: These results indicate that elevated baseline TG levels and PPARA gene intron 7 G/G genotype were associated with TG reduction > 30% after fenofibrate treatment in patients with type 2 diabetes.

Apolipoprotein E2↗
PubMed2004

Are cardiovascular disease and osteoporosis directly linked?

For years, osteoporosis and cardiovascular disease were thought to be two independent consequences of aging; however, mounting evidence supports an association between these diseases. Recently, a widespread class of cholesterol-lowering drugs known as statins have demonstrated (in rodents and cell cultures) the ability to induce bone formation. This finding is significant since current therapies are limited to the prevention or slowing down of bone loss rather than (enhancing/improving) bone formation. In humans, the ability of statins to generate new bone has not been consistent; however, several investigations have demonstrated a dramatic decrease in fracture risk. Although it has been proposed that statins induce new bone via increased bone morphogenetic protein-2, other conditions affected by statins such as dyslipidaemia, vascular calcification, endothelial dysfunction and impaired nitric oxide expression, may also contribute to the cardiovascular and bone health paradigm. Furthermore, the role of physical activity and its influence on cardiovascular and bone health, especially in postmenopausal women, may contribute to the discrepancy of findings in human data. In summary, it remains to be determined if statins contribute to bone health via improvements in vascular health or by pleiotropic properties unique to their pharmacology. This review provides information on our current understanding of the bone and cardiovascular association, as well as on novel areas of research to further our current understanding of these conditions.

Animals↗
PubMed2003

The prognostic importance of endothelial dysfunction and carotid atheroma burden in patients with coronary artery disease.

OBJECTIVES: The goal of this study was to determine the relative prognostic importance of noninvasive measures of endothelial function and atheroma burden in patients with coronary artery disease (CAD). BACKGROUND: Direct measurement of atherosclerosis by carotid ultrasound and endothelial function assessment by brachial artery flow-mediated dilation (FMD) have both been shown to predict vascular events. The combined prognostic utility of carotid ultrasound and FMD relative to traditional risk markers and cardiovascular fitness has not been evaluated. METHODS: A total of 152 patients with CAD underwent metabolic testing, exercise stress tests, carotid ultrasound, and endothelial function measurements. RESULTS: Patients were followed for 34 +/- 10 months during which 22 vascular events occurred. Peak FMD (p = 0.012) and FMD/nitroglycerin-mediated dilation (NMD) ratio (p = 0.008) were lower in subjects with events. Univariate analysis with Cox proportional hazards modeling identified plaque area (p = 0.0047), total area (p = 0.0085), peak FMD (p = 0.01), FMD/NMD ratio (p = 0.008), stress test workload (p = 0.027), long-acting nitroglycerin (NTG) (p = 0.0071), and calcium blockers (p = 0.0057) as predictors of adverse events. Multivariate analysis showed that FMD/NMD ratio (p < 0.0001), carotid plaque area (p = 0.06), and NTG (p = 0.005) were independent predictors. Based on median values, subjects were divided into high and low "plaque burden" groups and into high and low FMD/NMD subgroups. Patients with high FMD/NMD had low event rates irrespective of the degree of carotid atheroma. Patients with low FMD/NMD and high "plaque burden" had the highest event rate (p < 0.05). CONCLUSIONS: The structural and functional status of the vasculature are independent predictors of coronary events as shown by noninvasive measurement of endothelial function and carotid atheroma burden in patients with CAD. Preserved endothelial function attenuates the risk of future events associated with a high plaque burden.

Carotid Artery Diseases↗