[New AHA and ACC guidelines on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk : Statement of the D•A•CH Society for Prevention of Cardiovascular Diseases, the Austrian Atherosclerosis Society and the Working Group on Lipids and Atherosclerosis (AGLA) of the Swiss Society for Cardiology]. / Neue AHA- und ACC-Leitlinie zur Risikoreduktion von Herz-Kreislauf-Erkrankungen durch Cholesterinsenkung : Stellungnahme der D•A•CH-Gesellschaft Prävention von Herz-Kreislauf-Erkrankungen e. V., der Österreichischen Atherosklerose Gesellschaft und der Arbeitsgruppe Lipide und Atherosklerose (AGLA) der Schweizer Gesellschaft für Kardiologie.

Guidelines for the reduction of cholesterol to prevent atherosclerotic vascular events were recently released by the American Heart Association and the American College of Cardiology. The authors claim to refer entirely to evidence from randomized controlled trials, thereby confining their guidelines to statins as the primary therapeutic option. The guidelines derived from these trials do not specify treatment goals, but refer to the percentage of cholesterol reduction by statin medication with low, moderate, and high intensity. However, these targets are just as little tested in randomized trials as are the cholesterol goals derived from clinical experience. The same applies to the guidelines of the four patient groups which are defined by vascular risk. No major statin trial has included patients on the basis of their global risk; thus the allocation criteria are also arbitrarily chosen. These would actually lead to a significant increase in the number of patients to be treated with high or maximum dosages of statins. Also, adhering to dosage regulations instead of cholesterol goals contradicts the principles of individualized patient care. The option of the new risk score to calculate lifetime risk up to the age of 80 years in addition to the 10-year risk can be appreciated. Unfortunately it is not considered in the therapeutic recommendations provided, despite evidence from population and genetic studies showing that even a moderate lifetime reduction of low-density lipoprotein (LDL) cholesterol or non-HDL cholesterol has a much stronger effect than an aggressive treatment at an advanced age. In respect to secondary prevention, the new American guidelines broadly match the European guidelines. Thus, the involved societies from Germany, Austria and Switzerland recommend continuing according to established standards, such as the EAS/ESC guidelines.

Bevacizumab-associated hyperlipoproteinemia type IIb in a patient with advanced invasive-ductal breast cancer.

AIM: We report a case of bevacizumab-associated hyperlipoproteinemia in a patient with advanced breast cancer. CASE SUMMARY: A 57-year-old woman with advanced invasive-ductal breast cancer was administered bevacizumab from March 2008 to February 2009. Pretreatment laboratory showed borderline hypercholesterolemia (5.1 mmol/L, 197 mg/dL) and normal triglycerides (1.3 mmol/L, 115 mg/dL). Three months on treatment with bevacizumab, both serum cholesterol (11.9 mmol/L, 460 mg/dL) and triglycerides (7.4 mmol/L, 655 mg/dL) increased substantially, and remained well above the normal range for a period of bevacizumab treatment. From March 2008 to August 2008, the patient also received anticancer treatment with liposomal doxorubicin that was stopped early due to hand-foot syndrome. No concurrent hyperlipidemic drugs have been taken by the patient at the time of bevacizumab treatment. In February 2009, bevacizumab was stopped and the patient went on to receive paclitaxel for hepatic tumor progression. By December 2009, both serum triglycerides (1.3 mmol/L, 115 mg/dL) and cholesterol (3.2 mmol/L, 123 mg/dL) had normalized. DISCUSSION: This is the first published case of bevacizumab-associated hyperlipoproteinemia. By applying the Naranjo ADR probability scales, at least a possible relationship between hyperlipoproteinemia type IIb and bevacizumab in this patient is supported by the data (Naranjo score 4). No hyperlipidemic drugs were given concurrently with bevacizumab, and the serum cholesterol and triglycerides decreased quickly after bevacizumab was discontinued. CONCLUSIONS: This study describes a case of bevacizumab-associated hyperlipidemia. Patients receiving bevacizumab should have their cholesterol and triglycerides checked for potential worsening.

Combining bone resorption markers and heel quantitative ultrasound to discriminate between fracture cases and controls.

SUMMARY: This nested case-control analysis of a Swiss ambulatory cohort of elderly women assessed the discriminatory power of urinary markers of bone resorption and heel quantitative ultrasound for non-vertebral fractures. The tests all discriminated between cases and controls, but combining the two strategies yielded no additional relevant information. INTRODUCTION: Data are limited regarding the combination of bone resorption markers and heel quantitative bone ultrasound (QUS) in the detection of women at risk for fracture. METHODS: In a nested case-control analysis, we studied 368 women (mean age 76.2 +/- 3.2 years), 195 with low-trauma non-vertebral fractures and 173 without, matched for age, BMI, medical center, and follow-up duration, from a prospective study designed to predict fractures. Urinary total pyridinolines (PYD) and deoxypyridinolines (DPD) were measured by high performance liquid chromatography. All women underwent bone evaluations using Achilles+ and Sahara heel QUS. RESULTS: Areas under the receiver operating-characteristic curve (AUC) for discriminative models of the fracture group, with 95% confidence intervals, were 0.62 (0.56-0.68) and 0.59 (0.53-0.65) for PYD and DPD, and 0.64 (0.58-0.69) and 0.65 (0.59-0.71) for Achilles+ and Sahara QUS, respectively. The combination of resorption markers and QUS added no significant discriminatory information to either measurement alone with an AUC of 0.66 (0.60-0.71) for Achilles+ with PYD and 0.68 (0.62-0.73) for Sahara with PYD. CONCLUSIONS: Urinary bone resorption markers and QUS are equally discriminatory between non-vertebral fracture patients and controls. However, the combination of bone resorption markers and QUS is not better than either test used alone.

Insulin-like growth factor-I improves glucose and lipid metabolism in type 2 diabetes mellitus.

Hyperglycemia, hyperinsulinemia, and insulin resistance cause vascular disease in type 2 diabetes mellitus. Dietary treatment alone often fails and oral drugs or insulin enhance hyperinsulinemia. In previous studies, an intravenous bolus of recombinant human insulin-like growth factor-I (rhIGF-I) caused normoglycemia in insulin-resistant diabetics whereas rhIGF-I infusions lowered insulin and lipid levels in healthy humans, suggesting that rhIGF-I is effective in insulin-resistant states. Thus, eight type 2 diabetics on a diet received on five treatment days subcutaneous rhIGF-I (2 x 120 micrograms/kg) after five control days. Fasting and postprandial glucose, insulin, C-peptide, proinsulin, glucagon, triglyceride, insulin-like growth factor-I and -II, and growth hormone levels were determined. RhIGF-I administration increased total IGF-I serum levels 5.3-fold above control. During the control period mean (+/- SD) fasting glucose, insulin, C-peptide, and total triglyceride levels were 11.0 +/- 4.3 mmol/liter, 108 +/- 50 pmol/liter, 793 +/- 250 pmol/liter, and 3.1 +/- 2.7 mmol/liter, respectively, and decreased during treatment to a nadir of 6.6 +/- 2.5 mmol/liter, 47 +/- 18 pmol/liter, 311 +/- 165 pmol/liter, and 1.6 +/- 0.8 mmol/liter (P < 0.01), respectively. Postprandial areas under the glucose, insulin, and C-peptide curve decreased to 77 +/- 13 (P < 0.02), 52 +/- 11, and 60 +/- 9% (P < 0.01) of control, respectively. RhIGF-I decreased the proinsulin/insulin ratio whereas glucagon levels remained unchanged. The magnitude of the effects of rhIGF-I correlated with the respective control levels. Since rhIGF-I appears to improve insulin sensitivity directly and/or indirectly, it may become an interesting tool in type 2 diabetes and other states associated with insulin resistance.

Autoantibodies with antilipoprotein specificity and hypolipoproteinemia in patients with cancer.

Sera from 151 patients with a variety of cancers were screened for antibody-like activity against lipoproteins. Eighteen % of the sera exhibited activity against autologous and homologous high-density lipoproteins and 3% exhibited activity autologous and homologous low-density lipoprotiens. Antibody-like binding was proven by its restriction to the Fab fragment of IgG. The reactive part of the lipoprotein molecule was shown to be the appoprotein. Quantiation of the serum lipoproteins indicated that thehigh-density lipoprotien concentration in the sera of cancer patients was significantly lower (psmaller than 0.01) when antibody was present. These observation suggest that autoimmune mechanisms may be responsible for the decreased high-density lipoprotein serum levels in some patients with cancer.

Stimulus-response coupling in marine sponge cell aggregation: lipid metabolism and the function of exogenously added arachidonic and docosahexaenoic acids.

Cells of the marine sponge, Microciona prolifera, the most ancient of the animal cells which clump on recognition, resemble neutrophils and platelets in undergoing stimulus-response coupling when exposed to Ca2+ ionophores and phorbol esters. We have studied lipid content and remodelling in sponge cells by thin-layer, gas-liquid, and high-performance liquid chromatography (HPLC) analyses supplemented by ultraviolet and mass spectroscopy. Phosphatidylcholine (PC) (35.6%), phosphatidylethanolamine (PE) (27.4%) and phosphatidylserine (PS) (21.4%) constituted the bulk of phospholipids detected. The major fatty acids were all polyenoic; 22:6 (22%), 26:2 (17%) and 26:3 (15%). Arachidonic acid (20:4), present as 2.7% of total phospholipid, and docosahexanoic acid (22:6) were found to elicit aggregation of sponge cells when added (10 microM) in synergy with ionomycin (1 microM), resembling in their effects those of phorbol esters (but not phorbol) and 1-oleyl-2-acetylglycerol (OAG). Moreover, 20:4 and 22:6, as well as phorbol ester and OAG, overcame the block to aggregation imposed by colchicine and vinblastine. Kinetic studies of lipid remodelling showed that aggregating cells diverted [14C]22:6 or [14C]20:4 from triacylglycerol into diacylglycerol and phospholipids; appearance of label in phosphatidic acid and phosphatidylinositol (PI) anteceded labeling of phosphatidylcholine. In unstimulated cells, [14C]22:6 was rapidly incorporated into phosphatidylcholine with little accumulation in phosphatidate. Although 22:6 and 20:4 resembled OAG and phorbol esters in overcoming the effects of colchicine and vinblastine (which had no effects on overall lipid metabolism), they did not reverse the block to aggregation of nordihydroguaiaretic acid (NDGA) (which inhibited lipid metabolism). Under none of these circumstances was 22:6 or 20:4 converted to cyclooxygenase or lipoxygenase products in the course of aggregation: all labeled acyl groups remained present as unmodified fatty acids on alkaline hydrolysis. These data not only extend the observations of Muller et al. (J. Biol. Chem. 262 (1987) 9850-9858) on the role of phosphoinositides and C kinase in marine sponge cell aggregation, but also demonstrate that sponges form diacylglycerols in the process. We suggest that exogenous 22:6 and 20:4 (like phorbol esters or OAG) can substitute for endogenous diacylglycerol in the activation of protein kinase C.

Hypertriglyceridemia as a possible risk factor for prostate cancer.

We retrospectively studied anthropometric and laboratory parameters (including serum triglycerides, cholesterol), as well as comedication in 504 patients diagnosed with prostate cancer between January 1997 and August 2002 at a single referral center, and compared these patients with 565 age-matched patients with benign prostatic hyperplasia. A positive correlation was found between serum triglycerides and prostate cancer (odds ratio: 1.148/mmol/l; 95% confidence interval (CI) 1.003-1.315; P<0.05) after correcting for age, body mass index, diabetes and comedication with statins. Hypertriglyceridemia may increase the risk of prostate cancer, and the prognostic relevancy of serum triglycerides should be studied prospectively.

Antihypertensive therapy with Ca2+. Antagonist verapamil and/or ACE inhibitor enalapril in NIDDM patients.

OBJECTIVE: To assess the efficacy and tolerance of a diuretic-free antihypertensive therapy with a Ca2+ antagonist and an angiotensin-converting enzyme (ACE) inhibitor in patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: After a 2-wk washout and a 4-wk placebo phase, 47 hypertensive patients with NIDDM randomly received verapamil or enalapril alone and, if blood pressure remained elevated, both agents combined over 30 wk. RESULTS: Verapamil or enalapril alone normalized blood pressure to less than 90 mmHg diastolic in 30 patients; verapamil decreased mean +/- SE blood pressure from 159/98 +/- 3/1 to 146/87 +/- 3/2 mmHg (n = 18, P less than 0.001) and enalapril from 166/99 +/- 5/2 to 146/86 +/- 3/1 mmHg (n = 12, P less than 0.001). In 17 patients who were still hypertensive after 10 wk of monotherapy, combination of both drugs decreased blood pressure from 170/104 +/- 4/2 to 152/90 +/- 4/2 mmHg (P less than 0.001). Fasting plasma glucose, glycosylated hemoglobin, serum fructosamine, total lipids, high-density and low-density lipoprotein cholesterol, apolipoproteins A-I and B, creatinine, and urinary albumin-creatinine ratio were not significantly modified. CONCLUSIONS: In hypertensive patients with NIDDM, a diuretic-free therapy based on the Ca2+ antagonist verapamil and/or the ACE inhibitor enalapril can effectively decrease blood pressure without adversely affecting carbohydrate and lipid metabolism.

Premature atherosclerosis in HIV-infected individuals--focus on protease inhibitor therapy.

OBJECTIVE: Lipid disorders associated with the use of protease inhibitors may contribute to the premature development of atherosclerosis. The purpose of the present study was to determine whether the administration of a protease inhibitor-containing regimen to middle-aged (30-50 years) HIV-infected individuals for 6 months or longer is associated with an increased prevalence of atherosclerosis. METHODS: High-resolution B-mode ultrasound imaging was used to visualize the femoral and carotid arteries of 68 HIV-negative and 168 HIV-infected individuals, including 136 patients who had received protease inhibitors for 26.8 +/- 8.9 months (mean +/- SD). Atherogenic plaques were defined as a thickening of the intima-media > or = 1200 mm. RESULTS: The proportion of participants with one or more plaques was higher in the HIV-infected group in comparison with the HIV-negative group (55 versus 38%; P = 0.02), and so was the prevalence of cigarette smoking (61 versus 46%; P = 0.03) and hyperlipidaemia (56 versus 24%; P < 0.001). The presence of plaque was independently associated with age, male gender, plasma low-density lipoprotein cholesterol levels and smoking. In univariate logistic regression analysis, an association was also found with HIV infection. Among HIV-infected subjects protease inhibitor therapy was not associated with the presence of plaque. CONCLUSIONS: A large proportion of the middle-aged HIV-infected individuals examined during this study had one or more atherosclerotic plaques within the femoral or carotid arteries. The presence of peripheral atherosclerosis within this population is not associated with the use of protease inhibitors, but rather with 'classic' cardiovascular risk factors such as smoking and hyperlipidaemia, which are amenable to interventions.

Cardiovascular and metabolic profile during intervention with urapidil in humans.

Increased sympathetic activity or vascular reactivity to norepinephrine or both may play a complementary role in the pathogenesis of essential hypertension. Therefore, blood pressure regulation and metabolic correlates of cardiovascular risk were evaluated in 19 normal subjects and in 13 subjects with essential hypertension receiving placebo and after 4 weeks of intervention with urapidil, an agent that was found experimentally to exert a combined central sympathetic and peripheral alpha-adrenergic receptor inhibition. In hypertensive patients, urapidil normalized the initially low norepinephrine pressor dose (+ 106%), mildly increased basal plasma norepinephrine levels (+36%), and markedly shifted the plasma norepinephrine concentration-blood pressure response curve (p less than 0.01). Blood pressure was decreased (p less than 0.001). In normal subjects, urapidil produced only mild increases in norepinephrine plasma levels (+22%) and norepinephrine pressor dose (+38%) and no change in blood pressure. Body weight, exchangeable sodium, and blood volume were unaltered or increased slightly. Heart rate; plasma epinephrine, renin, angiotensin II, basal aldosterone, and electrolyte levels; plasma clearances of norepinephrine and angiotensin II; pressor effects of angiotensin II; chronotropic responses to isoproterenol or a norepinephrine-induced rise in blood pressure; and urinary prostaglandin F2 alpha excretion, as well as serum lipoprotein fractions and glucose, insulin, and uric acid levels, were not significantly modified by urapidil. Prostaglandin E2 excretion tended to be increased. Aldosterone responsiveness to angiotensin II was increased by urapidil in normal (p less than 0.05) but not in hypertensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum lipoproteins during treatment with the antihypertensive agent indapamide.

Considering the documented, potentially undesirable influence of various thiazide-type or loop diuretics on serum lipoproteins, we prospectively investigated in 69 men (mean age +/- SEM, 32 +/- 1 years) the metabolic effects of the new diuretic-antihypertensive compound indapamide. Compared to placebo, indapamide (2.5 mg/day) given for 6 to 8 weeks lowered (p less than 0.02 to less than 0.001) blood pressure (supine values from 148/98 +/- 3/2 to 137/93 +/- 3/2) in 29 men with mild to moderate essential hypertension, but not in 40 healthy men. In both groups, significant (p less than 0.05 to less than 0.001) decreases in body weight (-0.8 kg) and plasma potassium (-0.6 mmol/L), and increases in plasma uric acid (+20%), renin activity (+200%), and aldosterone documented good compliance. There were no significant changes in total cholesterol (in all subjects, from 208 +/- 6 to 213 +/- 6 mg/dl), low- or very low-density lipoprotein (VLDL) cholesterol (127 +/- 6 to 129 +/- 6 and 21 +/- 1 to 21 +/- 2 respectively), high-density lipoprotein cholesterol (50 +/- 1 to 51 +/- 1 mg/dl), total triglycerides (Tg) (108 +/- 5 to 112 +/- 6 mg/dl), VLDL-Tg, apoproteins A1 and A2, plasma glucose, epinephrine, norepinephrine, sodium, calcium, magnesium, and creatinine; apoprotein B (84 +/- 2 to 88 +/- 3 mg/dl) and plasma insulin after glucose loading dose tended to be increased minimally. The absence of distinct lipoprotein alterations after short-term indapamide treatment may be of clinical and epidemiological interest.

Cardiovascular effects of verapamil in essential hypertension.

Calcium antagonists may affect the regulation of body sodium and adrenergic-dependent mechanisms. Exchangeable sodium, blood volume, plasma norepinephrine, renin, aldosterone, pressor responsiveness to norepinephrine, heart rate responses to isoproterenol, and lipid metabolism were studied in 15 patients with essential hypertension after 8 weeks of treatment with verapamil (348 +/- 68 (SD) mg/day). Supine blood pressure decreased from 153/103 +/- 19/12 mm Hg to 140/95 +/- 14/12 mm Hg (P less than 0.01). Exchangeable sodium, blood volume, plasma norepinephrine, renin and aldosterone, serum total cholesterol, the lipoprotein fractions, and apoprotein levels were unchanged. The norepinephrine pressor and the isoproterenol chronotropic doses tended to increase, whereas the dose-response curve of blood pressure related to plasma norepinephrine was significantly displaced to the right (F = 5.34; P less than 0.05). The antihypertensive effect of verapamil is associated with a decreased cardiovascular pressor responsiveness to norepinephrine without changes in endogenous noradrenergic activity. Moreover, verapamil does not modify the sodium/fluid volume state, the activity of the renin-angiotensin aldosterone axis, or lipid metabolism.

Increased CSF levels of nerve growth factor in patients with Alzheimer's disease.

The authors quantitated CSF levels of nerve growth factor (NGF) in patients with AD, nondemented control subjects (CTR), and age-matched patients with major depression (DE). CSF levels of NGF were markedly higher in the AD group than in both the CTR and DE groups (p < 0.01 and p < 0.001). Increased CSF levels of NGF in AD patients may reflect reported accumulation of NGF in the AD brain and may constitute a candidate marker for clinical diagnosis and therapeutic monitoring.

Probucol in hypercholesterolemia. A double blind study.

The effect of Probucol on serum lipids, lipoproteins and the apoproteins A1, A2 and B was studied in 27 patients with primary hypercholesterolemia. After 3 months of dietary treatment and a 6 week placebo period the patients received 4 X 250 mg of Probucol or placebo per day for 4 months in a double blind design. Total and LDL-cholesterol were significantly reduced with Probucol (13% and 16% respectively) in addition to the diet. Apo B showed a 12% decrease. The HDL cholesterol concentration as well as the serum triglycerides and triglyceride-rich lipoproteins were not significantly altered. Both apo A1 and apo A2 were markedly reduced under Probucol treatment. In general the subjective and objective tolerance of the drug was good.

Reversal or prevention of diuretic-induced alterations in serum lipoproteins with betablockers.

In 18 patients with essential hypertension serum low density lipoprotein cholesterol (LDL-C) was significantly (P less than 0.001) increased following short-term chlorthalidone therapy, but not during combination therapy with chlorthalidone and a betablocker. This tendency was similar in two subgroups which were studied with an inverse sequence of drug administration. In Group I (11 men), a 22% increase (P less than 0.01) in LDL-C during chlorthalidone monotherapy was restored to normal 6 weeks after addition to a betablocker to the diuretic; in Group II (5 men, 2 postmenopausal women) LDL-C levels were increased by 41% (P less than 0.05) 6 weeks after withdrawal of the betablocker from the combination therapy. No significant changes occurred during either the treatment phase in high density lipoprotein cholesterol or apoprotein B levels. It is concluded that combination therapy with a betablocker may prevent or reverse an increase in serum LDL-C associated with short-term chlorthalidone monotherapy.

Anthropometric and lifestyle correlates of serum lipoprotein and apolipoprotein levels among normal non-smoking men and women.

The relationship between serologic predictors of coronary risk and anthropometric as well as lifestyle characteristics was investigated in 61 men (37.5 +/- 8.5 yrs) and 33 women (40.1 +/- 9.0 yrs). All subjects were healthy non-smokers, mostly middle-class bank employees. In bivariate analysis, among both genders the ratio of waist-to-hip circumference (WHR) was the single best predictor of levels of serum LDL-cholesterol, apolipoprotein B, VLDL-cholesterol and triglycerides (positive association) as well as HDL-cholesterol and apolipoprotein A-I (inverse association). In men, body fat as estimated from bioelectrical impedance measurement was the second best predictor of lipoprotein and apoprotein concentrations, whereas in women it was the body mass index (BMI). The additional independent predictive power of WHR and body fat for the lipid profile was tested in multivariate analysis by adding WHR and body fat sequentially to regression models containing already BMI, endurance capacity, exercise, alcohol consumption and age. For example, explained variance of triglyceride distribution rose from 26.3 to 35.1% (P = 0.01 for increase) when body fat was entered into the regression equation, or inclusion of WHR into a model already containing age, the behavioral variables, BMI, and body fat increased the explained variance of LDL/HDL-cholesterol ratio from 20.9 to 27.6% (P = 0.04 for increase). In women, the same regression models were even slightly more predictive for the serum lipid profile. Endurance capacity was related to a low atherogenic risk lipid profile in bivariate analysis but lost much of its predictive power in multivariate analysis, which confirms that the effect of fitness on lipid levels is probably mediated in part by a low body fat content. It is concluded from this cross-sectional investigation that studies which focus on associations between lifestyle and serologic predictors of atherogenic risk should possibly include the WHR and a measure of body fat, since the latter two appear to be closer correlates of serum lipoprotein and apolipoprotein levels than BMI or single behavioral factors, at least among male non-smokers.

Reduced LDL- and increased HDL-apoproteins in patients with hypercholesterolaemia under treatment with bezafibrate.

The effect of bezafibrate on serum lipids, lipoproteins and the apoproteins A-I, A-II and B was studied in 18 patients with primary hypercholesterolaemia. Total cholesterol was lowered by 20% (P less than 0.05), LDL-cholesterol by 24% (P less than 0.05), and apo B by 14% (P less than 0.05), which is comparable to the effect obtained with anion exchange resins but with far fewer side-effects. HDL increased significantly during bezafibrate treatment both by measurement of HDL-cholesterol (+54%, P less than 0.05) and by the determination of HDL-apoproteins A-I (+ 19%, P less than 0.05) and A-II (+ 23%, P less than 0.05). This increase of HDL and the decrease of triglycerides was maintained for 6 weeks of placebo treatment after cessation of bezafibrate, while serum total and LDL cholesterol as well as apo B returned to their baseline levels.

Apoproteins and lipids as discriminators of severity of coronary heart disease.

Serum apoprotein and lipid concentrations were measured in 63 patients undergoing coronary angiography. Thirty-eight patients had 50% or higher grade stenoses, 25 had chest pain, but no significant stenoses. Among the patients with higher grade stenoses 71% had hyperlipoproteinemias as opposed to 12% in patients without stenoses. As compared to suitable normal controls, patients with angiographically documented coronary heart disease showed significant changes in all lipid and apoprotein concentrations under study. However, differences between the two patients groups were also noted. Among these, apo A-I, A-II and B, total cholesterol and LDL cholesterol were statistically significant. These results indicate that apoprotein A and B levels, total cholesterol and LDL cholesterol are good discriminators of the severity of coronary heart disease, while HDL cholesterol is a more suitable parameter for epidemiological studies.

"Low dose" colestipol in children, adolescents and young adults with familial hypercholesterolemia.

The effect of colestipol on plasma lipids and lipoproteins was studied in children, adolescents and young adults with familial hypercholesterolemia. O.125 g or 0.25 g/kg body weight were given in randomized sequence for period of 4 weeks. Total cholesterol was lowered by 13 and 18% with the smaller and larger dose , respectively, and LDL cholesterol lowered by 15% with the smaller and 12% with the larger dose. HDL cholesterol rose by 18 an 32%. LDL composition before and during the study was abnormal due to a markedly reduced triglyceride content. "Low-dose" colestipol is less effective lowering total plasma and LDL cholesterol than conventional doses but may, due to very few side effects, by advantageously used in cases of familial hypercholesterolemia when plasma cholesterol levels after dietary management are only 15-20% above normal.

Effects of long-term, self-monitored exercise on the serum lipoprotein and apolipoprotein profile in middle-aged men.

To study the effects of long-term, self-monitored exercise on the serum lipid profile and body composition of middle-aged non-smoking males, a controlled study was conducted in 61 sedentary, middle-class Swiss men. Thirty-nine men were randomly allocated to jog 2 h/wk for 4 months on an individually prescribed, heart rate-controlled basis, whereas 22 men served as controls. Despite varying adherence to the exercise regimen, the following 4-month net changes (effect in exercise group minus effect in control group) in lipids were seen: HDL cholesterol (C) +0.12 mmol/l (95% CI 0.02, 0.22; P = 0.028), LDL-C +0.08 mmol/l (ns), VLDL-C -0.26 mmol/l (-0.45, -0.07; P = 0.009), total triglycerides (TT) -0.21 mmol/l (ns), HDL-C/total C +0.02 (0.001, 0.05; P = 0.047). The net changes in endurance capacity and resting heart rate in favour of exercisers were significant as well, whereas no significant changes in apolipoprotein levels were seen. Exploratory analyses revealed, for example, associations of the increase in total physical activity with an increase in the HDL-C/total C ratio (r = 0.46; P less than 0.001), and of the change in estimated body fat content with an opposed change in the HDL-C/total C ratio (r = -0.40; P less than 0.001), or an inverse relationship of the change in subcutaneous fat with a change in the HDL2-C level (r = -0.39; P less than 0.001). Multivariable regression analysis suggested that much of the effect of jogging on HDL-C was apparently mediated through a decrease in body fat content. A change in the waist/hip ratio was unrelated to lipoprotein changes but was related to the change of TT level (r = 0.22; P less than 0.05). This study confirms that individually prescribed, unsupervised jogging can increase HDL-C levels and improve the serum lipoprotein profile in self-selected nonsmoking males. Although the effect is modest, it may be relevant to preventive cardiology, given the evidence for a reduction in cardiovascular risk even after apparently small decreases in risk factor levels.