Tor Ole Klemsdal

Effect of diet or very long chain ω-3 fatty acids on progression of atherosclerosis, evaluated by carotid plaques, intima-media thickness and by pulse wave propagation in elderly men with hypercholesterolaemia:

Background This randomized study targeted a comparison of the effect of 3-year diet counselling or ω-3 polyunsaturated fatty acid (PUFA) supplementation (2.4g/day) on the progression of atherosclerosis in carotid arteries and on finger pulse wave propagation. Methods Measurements were assessed by high-resolution B-mode ultrasound and a photopletysmographic finger pulse-sensor, respectively. Altogether, 563 elderly men with long-standing hyperlipidaemia were randomized into four groups: controls (no dietary counselling and placebo); dietary counselling (and placebo); ω-3 PUFA supplementation (no dietary counselling); dietary counselling and ω-3 PUFA supplementation. Results In the diet only group, the carotid intima-media thickness increase (0.929 to 0.967 mm) was significantly less than in the control group (0.909 to 0.977 mm), (P=0.018). Significant increase in carotid plaques score and plaques area were observed in all four groups, but without between group differences. Changes in carotid intima-media thickness and in high-density lipoprotein-cholesterol were negatively correlated (adjusted P>0.001). Pulse wave propagation time decreased significantly in the control group (206 to 198 ms; P=0.002), reflecting reduced arterial elasticity. In the group receiving ω-3 PUFA only, pulse wave propagation time increased significantly when compared with the control group (P=0.013). Conclusion Reduced progression in carotid intima-media thickness was observed after dietary counselling, whereas ω-3 PUFA supplementation imposed a favourable effect on arterial elasticity. Eur J Cardiovasc Prev Rehabil 13:325-333

A randomized clinical trial on n-3 polyunsaturated fatty acids supplementation and all-cause mortality in elderly men at high cardiovascular risk:

Background The benefit of n-3 polyunsaturated fatty acids (PUFA) supplementation for mortality and cardiovascular events after myocardial infarction is well documented, but the effect of n-3 PUFA in Caucasians without established cardiovascular disease is not known. Our aim was to examine the influence of supplementation with eicosapentaenoic acid and docosahexaenoic acid on all-cause mortality and cardiovascular events in elderly men at high-risk of cardiovascular disease. Design In the Diet and Omega-3 Intervention Trial, 563 Norwegian men, 64–76-year old and 72% without overt cardiovascular disease, were randomized to a 3-year 2 × 2 factorial designed clinical trial of diet counseling and/or 2.4 g n-3 PUFA supplementation. The n-3 PUFA arm was placebo-controlled (corn oil). Methods Demographic parameters and classical risk factors were obtained at baseline. Deaths and cardiovascular events were recorded through 3 years, and the effects of n-3 PUFA-intervention on these outcomes were evaluated in pooled groups of the n-3 PUFA-arm. Results There were 38 deaths and 68 cardiovascular events. The unadjusted hazard ratios of all-cause mortality and cardiovascular events were 0.57 (95% confidence interval: 0.29–1.10) and 0.86 (0.57–1.38), respectively. Adjusted for baseline age, current smoking, hypertension, body mass index and serum glucose, hazard ratios were 0.53 (0.27–1.04, P = 0.063) and 0.89 (0.55–1.45, P = 0.641), respectively. Conclusion We observed a tendency toward reduction in all-cause mortality in the n-3 PUFA groups that, despite a low number of participants, reached borderline statistical significance. The magnitude of risk-reduction suggests that a larger trial should be considered in similar populations.

Effects of a low glycemic load diet versus a low-fat diet in subjects with and without the metabolic syndrome

BACKGROUND AND AIM Although many studies report benefits of low glycemic diets, the clinical effects as a whole are mixed. The study aim was to compare a low glycemic load (LGL) diet versus a low-fat diet in a trial with a moderately intense dietary intervention in subjects with varying degrees of metabolic syndrome. METHODS AND RESULTS Men and women aged 30-65 years, with a BMI of 28-40 kg/m(2) (28-35 for women) and at least one criterion of metabolic syndrome were randomized to the two diets. A total of 202 subjects were included, of which 126 (62%) had metabolic syndrome (>or=3 criteria). The completion rate was 81%. At 3 months, weight loss was greater in the LGL group (-4.8+/-3.9 kg versus -3.8+/-3.5 kg; P=0.06) compared to the low-fat group. At 1 year, however, weight loss was similar in both groups (-4.0+/-5.5 kg versus -4.3+/-6.2 kg; n.s.), but waist circumference reduction was less in the LGL group (-3.9+/-5.3 cm versus -5.8+/-6.8 cm; P=0.03). In contrast, diastolic blood pressure decreased significantly more in the LGL group (-4.0+/-8.7 mmHg versus -1.1+/-8.5 mmHg; P=0.02). We also observed a significant interaction between the presence of the metabolic syndrome and the effect of the two diets on waist circumference, with a less favorable effect of the LGL diet in subjects without the syndrome (P=0.039). CONCLUSION After 12 months, both diets reduced body weight and the metabolic disturbances similarly, but the LGL diet appeared more suitable for subjects with metabolic syndrome, and was less effective in those without it.

Effects of Selective Angiotensin II Type 1 Receptor Blockade with Losartan on Arterial Compliance in Patients with Mild Essential Hypertension

It has been suggested that antihypertensive drugs should not only decrease blood pressure, but also improve large artery compliance. The aim of the present study was to examine the effect of losartan, a selective angiotensin II type 1 receptor antagonist, on parameters reflecting arterial compliance. In a randomized, double-blind cross-over study, 16 patients with mild essential hypertension were examined after 4 weeks of treatment with placebo/losartan. The effect on finger plethysmographic arterial pulse curves were quantified by computing the relative height of the dicrotic notch, and pulse wave velocity was estimated by measurements of the time delay from the start of the QRS-complex (electrocardiogram) to the foot of the plethysmographic pulse wave. Compared with placebo, losartan reduced the relative height of the dicrotic notch from 55% (SD 12) to 47% [14] (p < 0.01), and pulse wave velocity from 9.3 m/sec to 8.7 m/sec (p < 0.05). The supine blood pressure decreased from 146/89 mmHg to 134/82 mmHg (p < 0.01). There was no correlation between the effects on blood pressure and the effects on the arterial compliance parameters, suggesting that losartan exerted an effect on arterial compliance beyond its effect on blood pressure.

Effect of a Low-Fat Versus a Low-Gycemic-Load Diet on Inflammatory Biomarker and Adipokine Concentrations

BACKGROUND Low-grade inflammation is linked to metabolic syndrome and obesity. We studied the effects of weight loss and dietary composition on serum concentrations of biomarkers of inflammation and adipokines. METHODS Men and women (n=181) aged 30-65 years with a body mass index (BMI) of 28-40 kg/m(2) (28-35 kg/m(2) for women) and one or more components of metabolic syndrome were randomized to follow one of two hypocaloric diets, a low-fat or low-glycemic-load diet for 3 months. Blood samples were taken pre- and postintervention. Serum concentrations of interleukin-6 (IL-6), tumor necrosis factorα (TNF-α), plasminogen activator inhibitor-1 (PAI-1), monocyte chemoattractant protein-1 (MCP-1), and adipokines (leptin, resistin, and adiponectin) were analyzed using multiplexed microsphere immunoassays. RESULTS Weight loss was not different in the low-fat (4.4%±3.8%) and low-glycemic-load (4.9%±3.2%) groups. Concentrations of IL-6, TNF-α, PAI-1, and leptin were significantly reduced in both dietary groups with no between-group differences, whereas MCP-1 and adiponectin concentrations did not change. Subjects with full metabolic syndrome (three or more components; n=109) experienced greater weight loss than subjects (n=72) with one to two components and greater reduction in leptin [7.08 (95% confidence interval 5.19, 8.97) vs. 3.46 (0.91, 6.00) ng/mL; p=0.02] and a tendency to greater reduction in TNF-α (1.00 [0.60, 1.44] vs 0.40 [0.02, 0.78] pg/mL; p=0.05). CONCLUSION Hypocaloric diets improved inflammatory biomarkers and adipokines independently of dietary composition. The response tended to be greater in subjects with three or more components of metabolic syndrome than their counterparts with one to two components.

Norway’s new principles for primary prevention of cardiovascular disease: age differentiated risk thresholds

Norway decided not to follow European guidelines on preventing cardiovascular disease and instead developed its own with age based thresholds. Ole Norheim and colleagues explain the rationale behind them

Physical distress is associated with cardiovascular events in a high risk population of elderly men

BackgroundSelf-reported health perceptions such as physical distress and quality of life are suggested independent predictors of mortality and morbidity in patients with established cardiovascular disease. This study examined the associations between these factors and three years incidence of cardiovascular events in a population of elderly men with long term hyperlipidemia.MethodsWe studied observational data in a cohort of 433 men aged 64–76 years from a prospective, 2 × 2 factorial designed, three-year interventional trial. Information of classical risk factors was obtained and the following questionnaires were administered at baseline: Hospital Anxiety and Depression Scale, Physical Symptom Distress Index and Life Satisfaction Index. The occurrence of cardiovascular death, myocardial infarction, cerebrovascular incidences and peripheral arterial disease were registered throughout the study period. Continuous data with skewed distribution was split into tertiles. Hazard ratios (HR) were calculated from Cox regression analyses to assess the associations between physical distress, quality of life and cardiovascular events.ResultsAfter three years, 49 cardiovascular events were registered, with similar incidence among subjects with and without established cardiovascular disease. In multivariate analyses adjusted for age, smoking, systolic blood pressure, serum glucose, HADS-anxiety and treatment-intervention, physical distress was positively associated (HR 3.1, 95% CI 1.2 – 7.9 for 3rd versus 1st tertile) and quality of life negatively associated (HR 2.6, 95% CI 1.1–5.8 for 3rd versus 1st tertile) with cardiovascular events. The association remained statistically significant only for physical distress (hazard ratio 2.8 95% CI 1.2 – 6.8, p < 0.05) when both variables were evaluated in the same model.ConclusionPhysical distress, but not quality of life, was independently associated with increased risk of cardiovascular events in an observational study of elderly men predominantly without established cardiovascular disease.Trial RegistrationTrial registration: NCT00764010

Effect of lifestyle and/or statin treatment on soluble markers of atherosclerosis in hypertensives

Objectives. To investigate the independent and combined effects of lifestyle changes and statin treatment on soluble markers of atherosclerotic activity. Design. The study was a randomised, 2×2 factorial 1 year intervention trial. Participants (n=177) were sedentary, drug-treated, hypertensive men (aged 40–74 years). They were randomised to placebo, lifestyle intervention (diet and physical activity), fluvastatin 40 mg, or the combination of lifestyle and fluvastatin. Results. Lifestyle intervention significantly reduced intercellular adhesion molecule-1 (sICAM-1) compared to usual care (p=0.003). Thrombomodulin level remained higher among individuals receiving lifestyle intervention (p=0.025). sICAM-1 was less reduced among fluvastatin treated participants compared to the placebo treated (p=0.029). Changes of blood pressure, weight or waist circumference were not significantly different between treatment groups. Individuals who achieved improvement of classical risk factors also had a significant reduction of endothelial markers (E-selectin, von Willebrands factor, tissue plasminogen activator antigen). Conclusions. One year of lifestyle intervention reduced the level of sICAM-1 in sedentary, drug-treated hypertensives, in spite of no impact on traditional risk factors. Low dose fluvastatin had no beneficial effect on the measured markers.

The influence of long-term awareness of hyperlipidemia and of 3 years of dietary counseling on depression, anxiety, and quality of life

OBJECTIVE The purpose of this study is to investigate the long-term effects of participation in a cardiovascular screening program and of dietary counseling on self-reported psychosocial outcomes and health concerns. METHODS High-risk subjects (n=563) with hyperlipidemia from the Oslo Diet and Antismoking Study (1972-1977) were reexamined after 25 years and randomly assigned to a new 3-year prospective 2x2 factorial placebo-controlled study in 1997 of n-3 polyunsaturated fatty acids and/or dietary counseling. Hospital Anxiety and Depression Scale (HADS), Life Satisfaction Index (LSI), and a new questionnaire on health concerns and behavior in response to risk information were collected at the 25-year follow-up. Hospital Anxiety and Depression Scale and LSI were evaluated at the end of the 3-year Diet and Omega-3 Intervention Trial on atherosclerosis (DOIT) in 505 subjects. RESULTS Twenty-five years after the screening program, HADS-anxiety was similar to the Norwegian norms (3.3 vs. 3.5), while HADS-depression was significantly lower (3.6 vs. 4.1, P<.01). Patients reported that 25 years of awareness of hyperlipidemia had influenced health concerns through a moderate change in diet habits, some restriction in life conduct, but an improvement of the total life situation. After a novel 3-year intervention in DOIT, there was no difference between the dietary counseling and control group with regard to anxiety, depression, or life satisfaction, but HADS-anxiety increased significantly (4.0 vs. 3.3, P<.001) in both groups. CONCLUSION Compared to the general population, screening-positive subjects did not have increased mental distress 25 years after screening, and beneficial health behavior persisted. Dietary counseling did not affect psychosocial outcomes.

The effect of transdermal nitroglycerin on exercise tolerance in relation to patch application time--a meta-analysis.

SummaryDisagreeing results have been reported in the many studies on continuous treatment with nitroglycerin patches. The effects on exercise tolerance are partly studied at the end of a 24-hour application period, and partly examined only a few hours after patch renewal. The present meta-analysis estimates the overall efficacy of nitroglycerin patches in trials with and without concomitant antianginal therapy, and investigates if the treatment effect depends on the patch application time. A computed search (MEDLINE) identified 110 publications, of which 17 trials on nitrate patch monotherapy and six trials on combined therapy satisfied the inclusion criteria. Data on ‘exercise duration’ and ‘ST-segment depression’ were converted to a standardized treatment effect size d, and pooled to an overall treatment effect size d+. In tests 2–5 hours after patch renewal, moderate but significant effects of nitrate monotherapy were observed; d+ was 1.20 with regard to ‘ST-segment depression’ and 0.39 with regard to ‘exercise duration’ (both p<0.0001). In contrast, 24 hours after patch application, the values for d+ were 0.09 (not significant) and 0.36 (p<0.01), respectively. When adding the results from the six trials on combined therapy, d+ with regard to ‘exercise duration’ was reduced to 0.28 (p<0.0001) 2–5 hours after renewal and to 0.17 (p=0.04) after 24 hours. Thus, the efficacy of continuous nitroglycerin patch treatment is moderate but evident during exercise tests 2–5 hours after patch renewal; however, it is reduced after 24 hours of patch application.