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Objectives: The goal of this study was to assess the predictive power of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and the decision cutoffs in heart failure (HF) across body mass index (BMI) categories., Background: Concentrations of NT-proBNP predict outcome in HF. Although the influence of BMI to reduce levels of NT-proBNP is known, the impact of obesity on prognostic value remains uncertain., Methods: Individual data from the BIOS (Biomarkers In Heart Failure Outpatient Study) consortium were analyzed. Patients with stable HF were classified as underweight (BMI <18.5 kg/m 2 ), normal weight (BMI 18.5-24.9 kg/m 2 ), overweight (BMI 25-29.9 kg/m 2 ), and mildly (BMI 30-34.9 kg/m 2 ), moderately (BMI 35-39.9 kg/m 2 ), or severely (BMI ≥40 kg/m 2 ) obese. The prognostic role of NT-proBNP was tested for the endpoints of all-cause and cardiac death., Results: The study population included 12,763 patients (mean age 66 ± 12 years; 25% women; mean left ventricular ejection fraction 33% ± 13%). Most patients were overweight (n = 5,176), followed by normal weight (n = 4,299), mildly obese (n = 2,157), moderately obese (n = 612), severely obese (n = 314), and underweight (n = 205). NT-proBNP inversely correlated with BMI (β = -0.174 for 1 kg/m 2 ; P < 0.001). Adding NT-proBNP to clinical models improved risk prediction across BMI categories, with the exception of severely obese patients. The best cutoffs of NT-proBNP for 5-year all-cause death prediction were lower as BMI increased (3,785 ng/L, 2,193 ng/L, 1,554 ng/L, 1,045 ng/L, 755 ng/L, and 879 ng/L, for underweight, normal weight, overweight, and mildly, moderately, and severely obese patients, respectively) and were higher in women than in men., Conclusions: NT-proBNP maintains its independent prognostic value up to 40 kg/m 2 BMI, and lower optimal risk-prediction cutoffs are observed in overweight and obese patients., Competing Interests: Funding Support and Author Disclosures Dr Januzzi is supported in part by the Hutter Family Professorship; is a Trustee of the American College of Cardiology; has received grant support from Novartis Pharmaceuticals, Roche Diagnostics, Abbott, Singulex and Prevencio; has received consulting income from Abbott, Janssen, Novartis, Pfizer, Merck, and Roche Diagnostics; and participates in clinical endpoint committees/data safety monitoring boards for Abbott, AbbVie, Amgen, Boehringer Ingelheim, Janssen, and Takeda. Dr Richards has sat on advisory boards and/or received speakers honoraria, travel support, and/or grants from Novartis, Roche Diagnostics, Abbott Laboratories, Thermo Fisher, and Critical Diagnostics. Dr Lam is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research support from Boston Scientific, Bayer, Roche Diagnostics, AstraZeneca, Medtronic, and Vifor Pharma; has served as consultant or on the Advisory Board/ Steering Committee/Executive Committee for Boston Scientific, Bayer, Roche Diagnostics, AstraZeneca, Medtronic, Vifor Pharma, Novartis, Amgen, Merck, Janssen Research & Development LLC, Menarini, Boehringer Ingelheim, Novo Nordisk, Abbott Diagnostics, Corvia, Stealth BioTherapeutics, JanaCare, Biofourmis, Darma, Applied Therapeutics, MyoKardia, WebMD Global LLC, Radcliffe Group Ltd, and Corpus. Dr Latini has received grant support and travel reimbursements from Roche Diagnostics. Dr Brunner-La Rocca reports unrestricted research grants and consulting fees from Roche Diagnostics, as well as unrestricted research grants from Novartis and GlaxoSmithKline outside this work. Dr Bayes-Genis has received grant support from Roche Diagnosis, lecture honoraria from Roche Diagnostics and Critical Diagnostics, and consulting income from Roche Diagnostics, Critical Diagnostics, and Novartis. Dr Lupón has received lecture honoraria from Roche Diagnostics and Critical Diagnostics. The University Medical Centre Groningen, which employs Drs De Boer and Meems, has received research grants and/or fees from AstraZeneca, Abbott, Boehringer Ingelheim, Cardior Pharmaceuticals Gmbh, Ionis Pharmaceuticals, Inc, Novo Nordisk, and Roche. Dr de Boer received speaker fees from Abbott, AstraZeneca, Bayer, Novartis, and Roche, outside the submitted work. Dr Gaggin has received grant support from Roche and Portola; consulting income from Roche Diagnostics, Amgen, and Ortho Clinical; and research payments for clinical endpoint committees for EchoSense and Radiometer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Celiac disease diagnostics begin by measuring autoantibodies, which may fail to identify seronegative patients. Duodenal lesion in the absence of antibodies is scarcely studied, especially in children., Aims: To investigate the prevalence and diagnostic outcomes of children with seronegative duodenal lesion in two countries with different disease profiles., Methods: Medical data, including the results of histology and transglutaminase (tTGab) and endomysium (EmA) antibody measurements were collected from 1172 Finnish and 264 Romanian children with systematic duodenal sampling. Database of 509 Finnish children with celiac disease was examined to identify earlier seronegative patients., Results: Celiac disease was diagnosed in 307 Finnish and 83 Romanian children in the endoscopy cohorts. No seronegative patients were found among 899 celiac disease patients, although some were only tTGab or EmA positive. Non-celiac duodenal lesion was detected in eight Finnish and 32 Romanian children, their most common diagnoses being inflammatory bowel disease and infections, respectively. Six children with morphological lesion received no diagnosis. None of them developed celiac disease during a follow-up of 3-11 years., Conclusion: Pediatric seronegative celiac disease is exceptional in the era of modern autoantibodies. Other reasons for duodenal lesion should therefore be sought, bearing in mind possible differences across countries., (Copyright © 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Both coronary microvascular dysfunction (CMD) and reduced exercise capacity are associated with adverse cardiovascular prognosis. The association between CMD and cardiopulmonary exercise testing (CPET) derived exercise capacity in symptomatic individuals without obstructive coronary artery disease (CAD) is not clear. We investigated whether exercise capacity was reduced in women with angina, CMD and no obstructive CAD compared with sex-matched controls. Furthermore, we assessed the association between CMD and other CPET-derived variables., Methods: All participants underwent transthoracic Doppler echocardiography of the left anterior descending artery with dipyridamole-induced vasodilation and CPET using ergometer cycle with an incremental test protocol., Results: We included 99 women with angina and no obstructive CAD (patients) and 27 asymptomatic women (controls), age (mean ± standard deviation) 61 ± 10 and 58 ± 10 years, respectively. Patients had a higher burden of risk factors compared with controls, while the weekly physical activity level was comparable between the groups (p = 0.72). CMD was present in 27 (27%) patients and 5 (19%) controls. Peak VO 2 was significantly reduced in patients with CMD compared with controls with normal coronary microvascular function ((median (IQR) 17.3 (15.5-21.3) vs. 27.3 (21.6-30.8) ml/kg/min; age-adjusted p = 0.001), independent of cardiovascular risk factors (p = 0.041). Presence of CMD in symptomatic women was also associated with diminished heart rate reserve (p < 0.001) and blunted heart rate recovery., Conclusions: Women with angina, CMD and no obstructive CAD have markedly reduced exercise capacity compared with sex-matched controls. Moreover, combination of angina and CMD is associated with impaired heart rate response and heart rate recovery., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: In a recent individual patient data meta-analysis, high-sensitivity troponin T (hs-TnT) emerged as robust predictor of prognosis in stable chronic heart failure (HF). In the same population, we compared the relative predictive performances of hs-TnT, N-terminal fraction of pro-B-type natriuretic peptide (NT-proBNP), hs-C-reactive protein (hs-CRP), and estimated glomerular filtration rate (eGFR) for prognosis., Methods and Results: 9289 patients (66 ± 12 years, 77% men, 85% LVEF <40%, 60% ischemic HF) were evaluated over a 2.4-year median follow-up. Median eGFR was 58 mL/min/1.73 m 2 (interquartile interval 46-70; n = 9220), hs-TnT 16 ng/L (8-20; n = 9289), NT-proBNP 1067 ng/L (433-2470; n = 8845), and hs-CRP 3.3 mg/L (1.4-7.8; n = 7083). In a model including all 3 biomarkers, only hs-TnT and NT-proBNP were independent predictors of all-cause and cardiovascular mortality and cardiovascular hospitalization. hs-TnT was a stronger predictor than NT-proBNP: for example, the risk for all-cause death increased by 54% per doubling of hs-TnT vs. 24% per doubling of NT-proBNP. eGFR showed independent prognostic value from both hs-TnT and NT-proBNP. The best hs-TnT and NT-proBNP cut-offs for the prediction of all-cause death increased progressively with declining renal function (eGFR ≥ 90: hs-TnT 13 ng/L and NT-proBNP 825 ng/L; eGFR < 30: hs-TnT 40 ng/L and NT-proBNP 4608 ng/L). Patient categorization according to these cut-offs effectively stratified patient prognosis across all eGFR classes., Conclusions: hs-TnT conveys independent prognostic information from NT-proBNP, while hs-CRP does not. Concomitant assessment of eGFR may further refine risk stratification. Patient classification according to hs-TnT and NT-proBNP cut-offs specific for the eGFR classes holds prognostic significance., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background and Aims: While a plethora of biomarkers have been shown to be associated with coronary artery disease, studies assessing biomarkers in coronary microvascular dysfunction (CMD) are few. We investigated associations between cardiovascular protein biomarkers and non-endothelium dependent CMD assessed by positron emission tomography (PET)., Methods: In 97 women with angina pectoris and no significant obstructive coronary artery disease (<50% stenosis on invasive coronary angiography), CMD was defined as myocardial blood flow reserve (MBFR) < 2.5 by rubidium-82 PET. Blood samples were analyzed with a cardiovascular disease proteomic panel encompassing 92 biomarkers. The relation between MBFR and biomarkers was evaluated with age-adjusted regression analysis., Results: Median age was 62 years (range 31-79), median MBFR was 2.7 (range 1.2-4.7) and 32% had non-endothelium dependent CMD (MBFR<2.5). Four biomarkers were significantly correlated with MBFR: Galectin-4 (Gal4, p = 0.008), growth differentiation factor 15 (GDF15, p = 0.026), tissue-type plasminogen activator (tPA, p = 0.030) and von Willebrand factor (vWF, p = 0.018), while 12 biomarkers showed a trend for correlation (0.05 ≤ p < 0.15). Of the 16 identified biomarkers, 10 are involved in pro-inflammatory pathways., Conclusions: In a panel of 92 cardiovascular protein biomarkers, 4 were significantly associated with non-endothelium dependent CMD in women: Gal4, GDF15, tPA and vWF, suggesting that inflammatory status and coagulation changes are associated with impaired microvascular dilatation. Further confirmatory studies are needed to corroborate these findings., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: The aim of this study is to obtain a deeper understanding of midwives' lived experiences of caring for new mothers with initial breastfeeding difficulties., Methods: A reflective lifeworld approach was used. Six midwives were recruited from a hospital in western Sweden. Data were collected via individual lifeworld interviews and analysed using phenomenological methods., Results: The essential meaning can be described as a midwife's wish to help new mothers reach their breastfeeding goals by trying to interact with them as individual women in unique breastfeeding situations. This wish constitutes a contradiction to the midwife's own desire to succeed in enabling mothers to breastfeed and the perceived risk of failure as a midwife if the mothers decide not to breastfeed. This is further described by five constituents: striving to provide individualised care, collegial and personal responsibility both enables and prevents care, a struggle to be sufficient, an uphill struggle and mutual joy becomes the motivation to care., Conclusions: Caring for new mothers with initial breastfeeding difficulties is a balancing act between the midwife's personal desire to succeed in enabling mothers to breastfeed, the mothers' wishes, the infants' needs, the importance of collective collegial competence and the limitations in the health care organisation. This makes the midwife's efforts to provide individualised care frustrating and demanding as well as motivating., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background.: Apnoeic oxygenation during anaesthesia has traditionally been limited by the rapid increase in carbon dioxide and subsequent decrease in pH. Using a Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE) technique a slower increase in carbon dioxide than earlier studies was seen. Notably, apnoeic oxygenation using THRIVE has not been systematically evaluated with arterial blood gases or in patients undergoing laryngeal surgery. The primary aim of this study was to characterize changes in arterial P O 2 , P CO 2 and pH during apnoeic oxygenation using THRIVE under general anaesthesia., Methods.: Adult patients, (ASA I-II), undergoing shorter laryngeal surgery under general anaesthesia, were oxygenated during apnoea using THRIVE, 100% oxygen, 40-70 litres min - 1 . A cohort was randomized to hyperventilate during pre-oxygenation. Vital parameters and blood gases were monitored., Results.: Thirty-one patients, age 51 (34-76) yr, BMI 25 (4) were included. Mean apnoea time was 22.5 (4.5) min. Patients were well oxygenated, S pO 2 was never below 91%. The increase in P aCO 2 and end-tidal CO 2 during apnoea was 0.24 (0.05) and 0.12 (0.04) kPa min -1 , respectively. Hyperventilation during pre-oxygenation generated no difference in P aCO 2 at the end of apnoea compared with normoventilation., Conclusions.: This physiological study of apnoeic oxygenation using THRIVE during laryngeal surgery shows that this technique is able to keep patients with mild systemic disease and a BMI <30 well oxygenated for a period of up to 30 min. The THRIVE concept makes it possible to extend the apnoeic window but monitoring of CO 2 and/or pH is recommended., Clinical Trial Registration.: NCT02706431., (© The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Background: Coronary microvascular function can be assessed by transthoracic Doppler echocardiography as a coronary flow velocity reserve (TTDE CFVR) and by positron emission tomography as a myocardial blood flow reserve (PET MBFR). PET MBFR is regarded the noninvasive reference standard for measuring coronary microvascular function but has limited availability. We compared TTDE CFVR with PET MBFR in women with angina pectoris and no obstructive coronary artery disease and assessed repeatability of TTDE CFVR., Methods: From a cohort of women with angina and no obstructive coronary artery stenosis at invasive coronary angiography, TTDE CFVR by dipyridamole induced stress and MBFR by rubidium-82 PET with adenosine was successfully measured in 107 subjects. Repeatability of TTDE CFVR was assessed in 10 symptomatic women and in 10 healthy individuals., Results: MBFR was systematically higher than CFVR. Median MBFR (interquartile range, IQR) was 2.68 (2.29-3.10) and CFVR (IQR) was 2.31 (1.89-2.72). Pearson's correlation coefficient was 0.36 (p<0.01). Limits of agreement (2·standard deviation) assessed by the Bland-Altman (confidence interval, CI) method was 1.49 (1.29;1.69) and unaffected by time-interval between examinations. Results were similar when adjusting for rate pressure product or focusing on perfusion of the left anterior descending artery region. Limits of agreement (CI) for repeated CFVR in 10 healthy individuals and in 10 women with angina was 0.44 (0.21;0.68) and 0.48 (0.22; 0.74), respectively., Conclusion: CFVR had a good repeatability, but the agreement between CFVR and MBFR was modest. Divergence could be due to methodology differences; TTDE estimates flow velocities whereas PET estimates myocardial blood flow., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: To assess whether the prognostic significance of cardiovascular (CV) biomarkers, is affected by renal dysfunction (RD) in systolic heart failure (HF)., Background: It is unknown, whether the prognostic significance of CV biomarkers, such as N-terminal-pro-brain-natriuretic-peptide (NT-proBNP), high-sensitive troponin T (hsTNT), pro-atrial natriuretic peptide (proANP), copeptin and pro-adrenomedullin (proADM), is affected by renal function in HF., Methods: Clinical data and laboratory tests from 424 patients with systolic HF were collected prospectively. The patients were followed for 4.5 years (interquartile range: 2-7.7 years). CV biomarkers were analyzed on frozen plasma, and renal function was estimated by the Modification of Diet in Renal Disease (MDRD) formula. Cox proportional hazard models for mortality risk were constructed and tests for interaction between each CV biomarker and RD were performed., Results: Median age was 73 years (51-83), 29% were female, LVEF was 30% (13-45), 74% were NYHA classes I-II and estimated glomerular filtration rate (eGFR) was 68 ml/min/1.73 m(2) (18-157). A total of 252 patients died. All five biomarkers--log(NT-proBNP) (HR: 2.13, 95% CI: 1.57-2.87:, P<0.001), hsTNT (HR: 3.07, 95% CI: 1.90-4.96 P<0.001), proANP (HR: 1.02, 95% CI: 1.01-1.03, P<0.001), copeptin (HR: 1.02, 95% CI: 1.01-1.03, P=0.008) and proADM (HR: 2.37, 95% CI: 1.66-3.38, P<0.001)--were associated with mortality risk, but not affected by RD (P>0.05 for all interactions)., Conclusion: Established and new CV biomarkers are closely associated with renal function in HF. However, their prognostic significance is not affected by RD, and all CV biomarkers can be used for risk stratification independently of renal function., (© 2013.)

A gas chromatography-high-resolution mass spectrometry (GC-HRMS) method using solid-phase microextraction (SPME) for the determination of 2,4,6-trichloroanisole (TCA) and 2,4,6-tribromoanisole (TBA) in wine at low ng L(-1) levels was developed. A robust SPME method was developed by optimizing several different parameters, including type of fiber, salt addition, sample volume, extraction and desorption time. The quantification limit for TCA and TBA in wine was lowered substantially using GC-HRMS in combination with the optimized SPME method and allowed the detection of low analyte concentrations (ng L(-1)) with good accuracy. Limits of quantification for red wine of 0.3 ng L(-1) for TCA and 0.2 ng L(-1) for TBA with gas chromatography-negative chemical ionization mass spectrometry and 0.03 ng L(-1) for TCA and TBA were achieved using GC-HRMS. The method was applied to 30 wines of which 4 wines were sensorically qualified as cork defected. TCA was found in three of these wines with concentrations in the range 2-25 ng L(-1). TBA was not detected in any of the samples.

The effects of albumin and human serum on the pharmacodynamics of faropenem were studied. The protein binding of faropenem was 91-95%, corresponding to the increase in MICs for Haemophilus influenzae in broth supplemented with albumin. Time-kill experiments in albumin-containing medium and in inactivated human serum 50% v/v showed that much higher drug concentrations were needed to achieve a bactericidal effect than were needed in broth. Active human serum alone exerted a strain-dependent bactericidal effect. It was concluded that it is the free fraction of faropenem in serum that has antibacterial activity against H. influenzae.

Background: The fatty acid composition of the diet is known to be partially reflected by the fatty acid composition of serum lipids., Objective: We examined whether pentadecanoic acid (15:0) in serum lipids can be used as a marker for intake of milk fat, the major dietary source of 15:0. We also investigated the relations between intake of milk fat and cardiovascular disease risk factors., Design: Sixty-two 70-y-old men completed 7-d dietary records. The intake of milk products was studied in relation to the proportions of 15:0 in serum cholesterol esters and phospholipids, as well as to the clinical characteristics of these men, by using Spearman's rank correlation., Results: The proportions of 15:0 in serum cholesterol esters were positively related to butter intake (r = 0.36. P = 0.004) and to the total amount of fat from milk products (r = 0.46, P < 0.0001): 15:0 in phospholipids was related to the amount of fat from milk and cream (r = 0.34, P = 0.008) and to the total amount of fat from milk products (r = 0.34, P = 0.008). Inverse associations were found between intake of milk products and body mass index, waist circumference, LDL-HDL ratio, HDL triacylglycerols, and fasting plasma glucose, whereas relations to HDL cholesterol and apolipoprotein A-I tended to be positive., Conclusions: The results suggest that 15:0 in serum can be used as a marker for intake of milk fat. The explanation for the inverse associations between the intake of milk products and certain cardiovascular risk factors is not known.

The compounds that cause off-flavours in plastics, have been recognized mainly as carbonyl compounds (aldehydes, ketones and esters). They occur in low concentrations, and due to their low-threshold odour concentrations, their typical odours were identified. Most of these off-flavour compounds are volatile. Chemical analysis of smelling compounds requires a very sensitive method with a high-resolution capability. The analysis of volatile organic compounds (VOCs) in high density polyethene (HD-PE) granules and waters in which the granules have been shaken for 4 h, were carried out by gas chromatography-mass spectrometry-sniffing system (GC-MS-SNIFF) and by gas chromatography-fourier transform infrared spectroscopy-sniffing system (GC-FTIR-SNIFF). A purge-and-trap technique was used to introduce the VOCs from samples into the gas chromatograph. Leaching waters of HD-PE granules were also evaluated by panel. This panel agreed upon six descriptive attributes for odour: sweet, chemical, stale, dusty, foul and floor-cloth. The attributes for taste were: sweet, metallic, stony, pungent, dusty, plastic, foul, stink bug and candle grease.

The effects of 3 wk on a diet rich in monounsaturated rapeseed oil were compared with those of a diet containing sunflower oil within a lipid-lowering diet. Ninety-five subjects with moderate hyperlipoproteinemia were randomly assigned to one of the two well-controlled diets prepared at the hospital kitchen. Total serum, low-density- and high-density-lipoprotein cholesterol concentrations decreased by 15%, 16%, and 11% (P < 0.001), respectively, on the rapeseed oil diet and by 16%, 14%, and 13% (P < 0.001) on the sunflower oil diet. Serum triglycerides decreased more markedly (by 29%, P < 0.001) on the sunflower oil than on the rapeseed oil diet (14%, P < 0.01). The n-3 fatty acids (20:5 and 22:5) in the serum phospholipids increased significantly on the rapeseed oil diet but decreased on the sunflower oil diet. There was an increase in the alpha-tocopherol concentrations after both diets. The findings indicate that low erucic acid rapeseed oil can replace oils and fats rich in polyunsaturated fatty acids in a lipid-lowering diet.

The aim of this study was to compare the effects of a diet enriched with monounsaturated (MUFAs) with one enriched with polyunsaturated (PUFAs) fatty acids on the serum lipoprotein composition in patients with hyperlipidemia. A new model for conducting controlled dietary treatment studies in free-living hyperlipidemic patients was tested. Twenty-six patients with an average age of 51 y participated in a crossover study during two consecutive 3.5-wk treatment periods. The mean serum cholesterol and LDL cholesterol decreased by 17% and 19%, respectively, on the MUFA diet. The corresponding figures on the PUFA diet were 19% and 23%, respectively. The HDL-cholesterol concentration was significantly decreased after both dietary periods. No significant differences in any of the variables studied were found between the diets. It is concluded that MUFAs and PUFAs, within a diet with a restricted content of saturated fat and total fat, are interchangeable with regard to lipid-lowering effects among free-living hyperlipidemic patients.

Controlled comparisons of the effects of monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) as a part of lipid-lowering diets in persons with hyperlipoproteinaemia are sparse. The present study was carried out at a metabolic ward. Forty hyperlipidaemic patients (25 hypercholesterolaemic and 15 hypertriglyceridaemic) were given a 3-week diet rich in either MUFA (saturated fatty acids 7.3 energy% (E%), MUFA 14.6 E%, PUFA 4.8 E%) or PUFA (saturated fatty acids 7.8 E%, MUFA 8.4 E%, PUFA 10.4 E%), but otherwise with an identical composition. The mean serum cholesterol reduction on the MUFA diet was 12% (P < 0.001), with a low density lipoprotein cholesterol reduction of 11% (P < 0.001). The corresponding reductions on the PUFA diet were 15% (P < 0.001) and 16% (P < 0.001). The serum apolipoprotein B and A-I concentrations decreased highly significantly by 13% and 11% on the MUFA diet and by 14% and 11% on the PUFA diet. None of these changes differed between the two diets. Neither were there any differences between the diets regarding the effects on blood glucose, serum insulin and plasma fibrinogen, but there was a significant decrease in serum insulin with a significant reduction of the insulin/glucose ratio after the MUFA diet. The results of this study indicate that MUFA and PUFA are interchangeable within the given frames in lipid lowering diets even in patients with hyperlipidaemia.

Nine hyperlipoproteinaemic patients were treated with a serum lipid-lowering diet during 4 weeks in a metabolic ward. The diet contained 35% energy from fat and the ratio between polyunsaturated and saturated fats (the P/S ratio) was 2.0. This treatment caused a reduction of the serum concentrations of the low density lipoprotein cholesterol (Chol) by 17% (P less than 0.01), of the apolipoprotein (apo) B by 27% (P less than 0.01), of high density lipoprotein (HDL) Chol by 15% (P less than 0.05) and of the apo A-I by 9% (P less than 0.02). The apo B/apo A-I ratio decreased by 19% (P less than 0.01). It is suggested that the reduced HLD Chol and apo A-I concentrations may be due to both the qualitative change to more polyunsaturated fats in the diet and to the reduction of the total dietary fat intake.

The fatty acid composition of the plasma lipid esters has been studied during lipid-lowering treatment of 95 patients with atherosclerotic disease. During the first two months of the trial only a diet was prescribed. During the ensuing two months either clofibrate or niceritrol, a nicotinic acid ester, was added in a randomized order. During the last two months the second drug was added. The combined treatment with diet, clofibrate and niceritrol caused highly significant serum lipid reductions. The fatty acid composition in the plasma lipid esters was determined in samples from each trial period to measure the degree of dietary adherence. During dietary treatment the relative content of saturated and monounsaturated fatty acids secreased and the polyunsaturated fatty acids increased with an increasing ratio between pulyunsaturated and saturated fatty acids (P/S ratio) in the cholesterol esters and triglycerides. Only minor changes were seen in the phospholipids. The changes caused by the diet were partly reversed by clofibrate while niceritrol did not cause any major changes of the fatty acid composition. Clofibrate treatment coincided with increasing amounts of monounsaturated fatty acids, especially oleate (18 : 1), in the cholesterol esters, triglycerides and phospholipids while there were significant reductions of the content of linoleic (18 : 2) acid in both the cholesterol esters and triglycerides. The 18 : 2/18 : 1 ratio decreased significantly in all the lipid esters analyzed. However, the P/S ratio was not significantly affected, partly because the relative content of saturated fatty acids also tended to decrease during clofibrate treatment. It is concluded that addition of clofibrate treatment to patients who are on a diet enriched with polyunsaturated fats is associated with a change from polyunsaturated to monounsaturated fatty acids in the plasma lipid esters but does not significantly effect the ratio between polyunsaturated and saturated fatty acids. The fatty acid changes caused by clofibrate treatment and counteracted by an increased amount of polyunsaturated fat in the diet.

The feasibility of reducing serum lipoprotein levels in patients with atherosclerotic disease by combining diet, clofibrate and nicotinic acid (niceritrol) has been investigated. An additive lipid-lowering effect of diet and the two drugs was demonstrated. It was possible to reduce the serum triglycerides (TG) in hypertriglyceridaemic patients by 50-60%. This corresponded to a reduction of very low density lipoprotein (VLDL) TG by 73 and 66% in patients with hyperlipoproteinaemia (HLP) type IIB and IV, respectively. In normotriglyceridaemic patients the serum TG concentration decreased by 30-40%. The serum cholesterol (Chol) concentration was reduced by 33% and the low density lipoprotein (LDL) Chol by 37% in HLP type IIA and IIB. The LDL Chol decreased by 32% in normolipoproteinaemic patients and by 21% in HLP type IV. The mean value for serum cholesterol after therapy was in all groups close to 200 mg/100 ml. In hypertriglyceridaemic patients high density lipoprotein (HDL) Chol increased by 18%. Clofibrate and niceritrol differed with regard to the effect on serum lipoprotein concentrations as well as on other metabolic parameters. Niceritrol was significantly more effective than clofibrate in lowering LDL Chol and in increasing HDL Chol. Niceritrol treatment significantly reduced the Chol/TG ratio in VLDL while no such effect was seen during clofibrate administration. The two drugs also showed significantly different effects on the fractional removal rate (K2) of triglyceride-rich lipoproteins as measured by the intravenous fat tolerance test (IVFTT). The K2 was significantly increased by clofibrate but was not affected by niceritrol treatment. The two drugs differed also with regard to the effects on serum uric acid concentration and the liver function tests. The plasma fibrinogen levels and the erythrocyte sedimentation rates were reduced during treatment with both niceritrol and clofibrate. The present study demonstrates that it is possible to obtain substantial reductions of serum lipoprotein concentrations by combining lipid-lowering diet, clofibrate and niceritrol treatment. There was an additive lipid-lowering effect of this treatment and the combination of the two drugs seemed beneficial in regard to certain possible side effects. The impact of a lipid reduction within this range on cardiovascular morbidity and mortality remains to be evaluated.