Hyperlipidemias: Frohlich J

McPherson R, Frohlich J, Fodor G, Genest J, Canadian Cardiovascular Society. · University of Ottawa Heart Institute, Ottawa, Canada. · Can J Cardiol. · Pubmed #16971976 links to  free full text

Abstract: 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.

Davidson MH, Ose L, Frohlich J, Scott RS, Dujovne CA, Escobar ID, Bertolami MC, Cihon F, Maccubbin DL, Mercuri M. · Chicago Center for Clinical Research, Chicago, Illinois 60610, USA. · Clin Cardiol. · Pubmed #14640465 No free full text.

Abstract: 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.

Frohlich J, Steiner G. · University of British Columbia, Vancouver, Canada. · Int J Clin Pract Suppl. · Pubmed #11965826 No free full text.

Abstract: Among the traditional risk factors, dyslipidaemia and coagulation disorders play an important role in increasing the risk of coronary heart disease (CHD) in patients with type 2 diabetes. The lipid abnormalities of patients with insulin resistance and type 2 diabetes include increased triglycerides, lower high density lipoprotein (HDL)-cholesterol and the predominance of small dense low density lipoprotein (LDL)-particles. The composition of HDL particles is different from healthy controls and the concentration of the larger, more anti-atherogenic particles is decreased in patients with insulin resistance and type 2 diabetes. Subgroup analyses of several large studies have shown that lowering LDL-cholesterol with statin treatment decreased cardiovascular events in patients with type 2 diabetes. In other studies, gemfibrozil decreased cardiovascular events in a subgroup of patients with diabetes, although the decreases were not always statistically significant. Platelets from patients with diabetes are more sensitive to several aggregating agents, have increased numbers of glycoprotein receptors and a lower activity of guanylate cyclase. These factors may contribute to the documented hyperreactivity of platelets in patients with type 2 diabetes. Other factors in patients with type 2 diabetes include alterations in serum fibrinogen, PAI-1, tissue-type plasminogen activator (tPa) and factors V, II and VII, which have all been linked to the risk of myocardial infarction. Increased D-dimer, von Willebrand factor (vWf) antigen, A-II anti-plasmin and decreased anti-thrombin III were also reported in patients with type 2 diabetes. This pro-thrombotic risk profile of the circulating blood in type 2 diabetes patients, together with the lipid abnormalities, contributes to the increased risk of vascular events in this population.

Sniderman AD, Frohlich J. · McGill University, Royal Victoria Hospital, Montreal, Canada. · Can J Cardiol. · Pubmed #10692659 No free full text.

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Lichtenstein AH, Ausman LM, Jalbert SM, Vilella-Bach M, Jauhiainen M, McGladdery S, Erkkilä AT, Ehnholm C, Frohlich J, Schaefer EJ. · Cardiovascular Nutrition Research Program and Lipid Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA. · J Lipid Res. · Pubmed #11861668 links to  free full text

Abstract: 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.

Levin A, Duncan L, Djurdjev O, Shapiro RJ, Frohlich J, Belanger A, Dumas R, Ross S. · Division of Nephrology, University of British Columbia, Vancouver, Canada. · Clin Nephrol. · Pubmed #10711416 No free full text.

Abstract: BACKGROUND: Renal insufficiency is characterized by lipoprotein abnormalities including elevated triglyceride levels. PATIENTS AND METHODS: The safety and efficacy of micronized fenofibrate as a treatment for dyslipidemia in patients with progressive renal insufficiency was evaluated in a randomized, placebo-controlled double-blind study comparing fenofibrate and dietary modification to dietary modification alone. Patients were evaluated following a 3-month pre-randomization period of dietary counseling. Twenty-eight patients with moderate renal insufficiency and triglyceride levels 2.3 mmol/l or LDL/HDL ratio 5 were randomized to placebo (n = 12) or fenofibrate (n = 16) therapy. Treatment and dietary counseling continued for 6 months. RESULTS: Ten of 16 patients (63%) treated with fenofibrate achieved a 30% reduction in triglyceride levels or LDL/HDL ratio reduction < 5 compared to 2 of 17% in the placebo group (p = 0.015). Triglyceride levels were significantly reduced in the fenofibrate group (-31%) versus placebo (+1.3%, p = 0.003). In compliant patients (n = 25) there was also a significantly greater increase in HDL cholesterol levels in the fenofibrate group (+19.9%) compared to placebo (-4.7%, p = 0.001). Changes in measured creatinine clearance were not significantly different between the groups and there were no serious adverse effects of treatment. CONCLUSION: Fenofibrate therapy combined with dietary modification effectively reduced triglyceride levels in renal insufficiency patients without serious adverse effects.

Aminbakhsh A, Frohlich J, Mancini GB. · Department of Medicine, University of British Columbia, St Paul's Hospital. · Clin Invest Med. · Pubmed #10664868 No free full text.

Abstract: PURPOSE: To examine the relation between carotid artery (CA) intima-media thickness (IMT) assessed by B mode ultrasonography (US), presence of plaques and major risk factors in a population without known vascular disease. Alternative methods of quantifying US results and implications for starting lipid-lowering therapy were also explored. DESIGN: Prospective study. SETTING: Specialized lipid clinic. PATIENTS: One hundred and sixty patients with hyperlipidemia but without symptomatic coronary or peripheral vascular disease were examined by US, of whom 92 patients with normal blood pressure who were not receiving lipid-lowering treatment were included in the analysis. INTERVENTIONS: B mode US of the CA was performed. Measurements were made of the IMT of the right and left common CA, and the average IMT (AIMT) was calculated. The number of plaques (PN) in the CA and its bifurcations was counted, and the average total thickness (ATT), the total area (TA), and average plaque thickness (APT) were calculated. RESULTS: Stepwise regression analysis showed that age, the ratio of total cholesterol to high-density-lipoprotein cholesterol, weight and smoking significantly predicted ATT, APT and PN. By contrast, age, weight and apo B levels predicted AIMT. Detection of patients with CA abnormalities was improved by incorporating plaque dimensions: AIMT had a 63% sensitivity in detecting CA abnormalities, whereas TA had a sensitivity of 72%. CONCLUSION: Indices of CA atherosclerosis that integrate the contribution of plaque to overall atheroma burden are related to known risk factors and are more sensitive than AIMT for detection of abnormalities.

Al Riyami NB, Frohlich J. · Department of Medical Biochemistry, University of British Columbia, St Paul's Hospital, Vancouver, Canada V6Z 1Y6. · Clin Biochem. · Pubmed #18454939 No free full text.

Abstract: We report a case of unexpected extreme hypertriglyceridemia in a 32 year old man following 5 days of intravenous heparin infusion. We believe the cause of the elevation is mainly due to a temporary depletion of lipoprotein lipase caused by heparin. To the best of our knowledge, this is the first case report of such an extreme elevation in triglycerides following prolonged intravenous heparin infusion. The clinical history and details of the suggested mechanism of the hypertriglyceridemia are discussed in this case report.

Wiesinger HA, Shah J, White A, Yoshida EM, Frohlich J, Sirrs S, Gill S, Byrne MF. · Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. · Ann Hepatol. · Pubmed #18376368 No free full text.

Abstract: BACKGROUND: The metabolic syndrome and non-alcoholic fatty liver disease are increasing at alarming rates. AIMS: To determine the effect of HMG-CoA reductase inhibitors (statins) on elevated liver enzymes in patients with hyperlipidemia. PATIENTS: Patients with AST above 60 U/L prior to or during treatment with statin therapy at a quaternary care lipid clinic were reviewed. METHODS: A retrospective analysis was conducted. Patients were separated into two groups: Group 1--elevated AST prior to statin therapy; and Group 2--elevated AST during statin therapy. RESULTS: Forty six patients with one or more measurements of AST >60 U/L remained after exclusion criteria were applied. Ten of 13 (77%) group 1 patients had reduced AST levels after initiation of statin therapy. Thirty two of 33 patients (97%) in group 2 had transient AST elevations while on statin therapy; one patient had persistently elevated AST after initiation of treatment. There were no significant adverse events reported. CONCLUSION: Use of HMG-CoA reductase inhibitors in patients with elevated AST resulted in normalization of AST levels. HMG-CoA reductase inhibitors were safe in patients with mildly elevated AST. This may translate to use of HMG-CoA reductase inhibitors in diseases such as non-alcoholic fatty liver disease and non-alcoholic steatohepatitis.

Awan Z, Alrasadi K, Francis GA, Hegele RA, McPherson R, Frohlich J, Valenti D, de Varennes B, Marcil M, Gagne C, Genest J, Couture P. · McGill University Health Center/Royal Victoria Hospital, 687 Pine avenue West, Montréal, QC H3A 1A1, Canada. · Arterioscler Thromb Vasc Biol. · Pubmed #18239150 links to  free full text

Abstract: BACKGROUND: Patients with homozygous familial hypercholesterolemia (hmzFH) attributable to LDL receptor gene mutations have shown a remarkable increase in survival over the last 20 years. Early onset coronary heart disease (CHD) and calcific aortic valve stenosis are the major complications of this disorder. We now report extensive premature calcification of the aorta in patients with hmzFH. METHODS AND RESULTS: We examined 25 hmzFH patients from Canada; mean age was 32 years (range 5 to 54), and mean baseline cholesterol before treatment was 19+/-5 mmol/L (737+/-206 mg/dL). Aortic calcification was quantified using computed tomography (CT). An elevated mean calcium score was found in patients by age 20 and correlated with age (r(2)=0.53, P=0.001). One quarter (24%) of patients underwent aortic valve surgery. CONCLUSIONS: We document premature severe aortic calcifications in all adult hmzFH patients studied. These presented considerable surgical management challenges. Strategies to identify and monitor aortic calcification in hmzFH by noninvasive techniques are required, as are clinical trials to determine whether additional or more intensive therapies will prevent the progression of such calcifications. Whether vascular calcifications in hmzFH subjects are related to sustained increases in LDL-C levels or to other mechanisms, such as abnormal osteoblast activity, remains to be determined.

Staples J, Taylor P, Magil A, Frohlich J, Johnston SM, Koschinsky M, Chan-Yan C, Levin A. · University of British Columbia, Room 6010A 1081 Burrard, Vancouver BC V6Z 1Y8, Canada. · Nephrol Dial Transplant. · Pubmed #18199694 No free full text.

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Bar SL, Holmes DT, Frohlich J. · Division of Cardiac Surgery, Vancouver General Hospital, British Columbia. · Can Fam Physician. · Pubmed #17872677 links to  free full text

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Vaverkova H, Karasek D, Novotny D, Jackuliakova D, Halenka M, Lukes J, Frohlich J. · 3rd Department of Internal Medicine, University Hospital Olomouc, 775 20 Olomouc, Czech Republic. · Atherosclerosis. · Pubmed #17714716 No free full text.

Abstract: The aim of our study was to evaluate the relationship of adiponectin to soluble forms of vascular cell adhesion molecule-1 (sVCAM-1) and intercellular cell adhesion molecule-1 (sICAM-1) in patients with cardiovascular disease or dyslipidemia. Two hundred and sixty-four patients (134 men/130 women, mean age 43.8+/-14.8/46.0+/-14.9 years) of Lipid Center, University Hospital Olomouc, off hypolipidemic therapy for at least 6 weeks, participated in the study. In multiple regression analysis, adiponectin was independently positively associated with serum HDL-cholesterol (p<0.0001) and sVCAM-1 (p<0.0001), female gender (p<0.0001) and negatively with hs-CRP (p=0.014). Serum concentration of adiponectin and sICAM-1 did not correlate but sICAM-1 was independently, positively associated with sVCAM-1 (p<0.0001) and negatively with markers of insulin resistance and inflammation, namely atherogenic index log[triglycerides/HDL-cholesterol] (p<0.0001), hs-CRP (p<0.001) and HOMA (p<0.05). Positive association of adiponectin with HDL-C and negative association with hs-CRP indicate anti-atherogenic properties of adiponectin. The finding of the positive association of adiponectin with sVCAM-1 in patients at risk is unexpected. We hypothesize that adiponectin may be involved (directly or indirectly) in shedding of ectodomains of VCAM-1 from endothelial surface and in this way down-regulates their effects. This process may be protective in the initial stages of atherosclerosis.

Barter PJ, Ballantyne CM, Carmena R, Castro Cabezas M, Chapman MJ, Couture P, de Graaf J, Durrington PN, Faergeman O, Frohlich J, Furberg CD, Gagne C, Haffner SM, Humphries SE, Jungner I, Krauss RM, Kwiterovich P, Marcovina S, Packard CJ, Pearson TA, Reddy KS, Rosenson R, Sarrafzadegan N, Sniderman AD, Stalenhoef AF, Stein E, Talmud PJ, Tonkin AM, Walldius G, Williams KM. · Heart Research Institute, Camperdown, Sydney, NSW, Australia. · J Intern Med. · Pubmed #16476102 No free full text.

Abstract: There is abundant evidence that the risk of atherosclerotic vascular disease is directly related to plasma cholesterol levels. Accordingly, all of the national and transnational screening and therapeutic guidelines are based on total or LDL cholesterol. This presumes that cholesterol is the most important lipoprotein-related proatherogenic risk variable. On the contrary, risk appears to be more directly related to the number of circulating atherogenic particles that contact and enter the arterial wall than to the measured concentration of cholesterol in these lipoprotein fractions. Each of the atherogenic lipoprotein particles contains a single molecule of apolipoprotein (apo) B and therefore the concentration of apo B provides a direct measure of the number of circulating atherogenic lipoproteins. Evidence from fundamental, epidemiological and clinical trial studies indicates that apo B is superior to any of the cholesterol indices to recognize those at increased risk of vascular disease and to judge the adequacy of lipid-lowering therapy. On the basis of this evidence, we believe that apo B should be included in all guidelines as an indicator of cardiovascular risk. In addition, the present target adopted by the Canadian guideline groups of an apo B <90 mg dL(-1) in high-risk patients should be reassessed in the light of the new clinical trial results and a new ultra-low target of <80 mg dL(-1) be considered. The evidence also indicates that the apo B/apo A-I ratio is superior to any of the conventional cholesterol ratios in patients without symptomatic vascular disease or diabetes to evaluate the lipoprotein-related risk of vascular disease.

Holmes DT, Schick BA, Humphries KH, Frohlich J. · St. Paul's Hospital Lipid Clinic and the University of British Columbia Department of Pathology and Laboratory Medicine, Vancouver, Canada. · Clin Chem. · Pubmed #16141286 links to  free full text

Abstract: 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.

Vaverkova H, Frohlich J, Jackuliakova D, Novotny D. · 3rd Clinic of Internal Medicine, University Hospital and Medical Faculty of Palacky University, Olomouc, Czech Republic. · Clin Biochem. · Pubmed #15885228 No free full text.

Abstract: 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.

Genest J, McPherson R, Frohlich J, Fodor G. · Division of Cardiology, Royal Victoria Hospital, McGill University, Montréal, Que. · CMAJ. · Pubmed #15824410 links to  free full text

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Genest J, Frohlich J, Fodor G, McPherson R, Anonymous00240. · Royal Victoria Hospital, McGill University, Montréal, Que. · CMAJ. · Pubmed #14581310 links to  free full text

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Sniderman AD, Lamarche B, Tilley J, Seccombe D, Frohlich J. · Mike Rosenbloom Laboratory for Cardiovascular Research, McGill University Health Centre, McGill University, Montreal, Canada. · Diabetes Care. · Pubmed #11874951 links to  free full text

Abstract: 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.

Miremadi S, Sniderman A, Frohlich J. · Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, V6Z 1Y6, Canada. · Clin Chem. · Pubmed #11861438 links to  free full text

Abstract: 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.

Sniderman AD, Bergeron J, Frohlich J. · Laboratory for Cardiovascular Research, McGill University Health Centre, Royal Victoria Hospital, 687 Pine Ave. W, Montreal QC H3A 1A1. · CMAJ. · Pubmed #11209748 links to  free full text

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Dobiásová M, Frohlich J. · Fyziologický ústav Akademie vĕd Ceské republiky, Praha. · Vnitr Lek. · Pubmed #11048517 No free full text.

Abstract: The new atherogenic plasma index (AIP) is a logarithmic transformation of the ratio of the molar triglyceride (TG) concentration and high density lipoprotein cholesterol (HDL-C). AIP correlates closely with the size of LDL particles (r = 0.8) and esterification rate of plasma cholesterol devoid of apo B lipoproteins (FERHDL), r = 0.9 which are considered at present the most sensitive indicators of the atherogenic plasma profile. AIP was recommended by the authors, based on analysis of results of 11 previous studies (1156 subjects) where FERHDL and plasma lipid parameters were investigated in different groups of people who differed as to the atherogenic risk. The AIP index was moreover used for evaluation of a clinical study comprising 609 patients with hyperlipidaemia, who were treated for three months with ciprofibrate (Lipanor). The mean AIP values of non-risk groups (plasma from umbilical blood, children, healthy women etc.) equalled zero or were lower, while with an increasing atherogenic risk (men, women after the menopause) AIP reached positive values, incl. high positive values in risk groups (plasma of diabetic subjects, patients with HLP, patients with positive angiography, myocardial infarction etc.). In all groups women had lower AIP values as compared with males. In patients after Lipanor therapy the AIP declined (from 0.58 +/- 0.17 to 0.33_0.18 in men, from 0.50 +/- 0.18 to 0.21 +/- 0.19 in women). If we consider AIP values from negative ones to 0.15 as "safe" from the aspect of atherogenicity, before Lipanor treatment these "safe" levels were recorded in 1.5% men and in 5.2% women and after treatment in 32% men and 48% women. The results indicate, that AIP which reflects the plasma lipoprotein profile quantifies the relations between TG and HDL-C and thus can be an objective indicator of the atherogenic risk and effectiveness of treatment and it is useful because it can be assessed in any surgery.

Holmes DT, Long P, Frohlich J. · No affiliation provided · Am J Psychiatry. · Pubmed #15994726 links to  free full text

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Fung M, Bebb R, Frohlich J. · No affiliation provided · Lancet. · Pubmed #11784667 No free full text.

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Frohlich J, Sniderman A. · No affiliation provided · Arterioscler Thromb Vasc Biol. · Pubmed #11742892 links to  free full text

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