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.

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.

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

BACKGROUND: Self-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. METHODS: We studied observational data in a cohort of 433 men aged 64-76 years from a prospective, 2 x 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. RESULTS: After 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. CONCLUSION: Physical 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 REGISTRATION: Trial registration: NCT00764010.

Relationship between obesity, smoking, and the endogenous nitric oxide synthase inhibitor, asymmetric dimethylarginine.

We investigated the levels of asymmetric dimethylarginine (ADMA), an important endogenous inhibitor of nitric oxide (NO), as related to metabolic risk factors known to contribute to atherosclerotic disease. Dimethylarginines were analysed in a cross-sectional study of 563 elderly high-risk men (70 +/- 6 years). ADMA and the l-arginine/ADMA (l-arg/ADMA) ratio were highly significantly correlated with several metabolic risk factors. However, only the association with body mass index (BMI) remained significant after adjustment for inter-related variables. When analyzing the results according to being overweight or not, ADMA levels were independently significantly higher (P = .05) and the L-arg/ADMA ratios were significantly lower (P < .008) in individuals with high BMI (> or =26 kg/m(2), median value) as compared with subjects with low BMI. ADMA levels were furthermore significantly lower (P = .037) and L-arginine and the l-arg/ADMA ratios were significantly higher (P = .004 and P = .001, respectively) in smokers compared with nonsmokers, the latter being independent of other risk factors. The strong relationship found between BMI and plasma levels of ADMA and the l-arg/ADMA ratio indicate a link to endothelial dysfunction in overweight subjects. The beneficial dimethylarginine profile observed in smokers in this elderly population is not easily explainable and should be further investigated.

Dietary and antismoking advice and ischemic heart disease mortality in men with normal or high fasting triacylglycerol concentrations: a 23-y follow-up study.

BACKGROUND: In the Oslo Diet and Antismoking Trial, 1232 high-risk men aged 40-49 y were randomly assigned to either a lifestyle intervention group or a control group for 5 y. The study showed a significant reduction in ischemic heart disease (IHD) events in the intervention group. OBJECTIVE: Our objective was to examine this cohort 23 y after the start of the trial. DESIGN: We examined the effect of group assignment on IHD mortality in subjects with a normal (below the median; range: 0.69-2.00 mmol/L; n = 615) or a high (at or above the median; range: 2.01-13.80 mmol/L; n = 617) fasting triacylglycerol concentration in 1972-1973 (at inclusion into the study). We recorded vital status on 31 December 1996 and ascertained causes of death by linkage to Statistics Norway. RESULTS: In the men with a high triacylglycerol concentration, IHD death occurred in 25 (8.13%) subjects in the intervention group and in 44 (14.2%) subjects in the control group (relative risk: 0.57; 95% CI: 0.36, 0.91; P = 0.02). An adjusted Cox proportional hazards model yielded a hazard ratio of 0.56 (95% CI: 0.34, 0.93; P = 0.027). In the men with a normal triacylglycerol concentration, the intervention had no detectable effect on IHD mortality (adjusted hazard ratio: 1.10; 95% CI: 0.66, 1.83; P = 0.7). CONCLUSIONS: These data suggest that advice to change diet and smoking habits reduced the relative risk of IHD mortality after 23 y in men with high triacylglycerol concentrations. Men with normal triacylglycerol concentrations did not appear to achieve this long-term benefit of lifestyle intervention.

Supplementation with fish oil affects the association between very long-chain n-3 polyunsaturated fatty acids in serum non-esterified fatty acids and soluble vascular cell adhesion molecule-1.

We have investigated the effect of fish oil supplementation on the association between serum non-esterified fatty acid (NEFA) pattern and atherosclerotic activity. We studied correlations between serum non-esterified very long-chain eicosapentaenoic (EPA), docosahexaenoic acid (DHA) and arachidonic acid (AA) and biochemical markers of endothelial activation before and after 18-months intervention with fish oil supplementation. The fish oil supplementation consisted of 2.4 g of EPA and DHA per day, with corn oil as placebo. Elderly men ( n =171) with high risk for coronary heart disease were divided into four intervention groups in a factorial design: fish oil supplementation ( n =44), dietary intervention ( n =42), fish oil supplementation+dietary intervention ( n =47) or placebo ( n =38). The composition of fasting NEFA was analysed before and after intervention by GLC. Circulating endothelial markers were analysed by ELISA. A statistically significant positive correlation between the change in serum non-esterified DHA and soluble vascular cell adhesion molecule-1 (sVCAM-1) was found in the pooled group that received fish oil supplementation ( n =91; Spearman's correlation coefficient r =0.24, P =0.02). No such correlation was found in the pooled group without fish oil supplementation ( n =80). Furthermore, there was a significant negative correlation between the change in serum non-esterified EPA and the relative change in sVCAM-1 in the group that did not receive fish oil supplementation ( r =-0.34, P =0.002). No such correlation was found in the group with fish oil supplementation. We conclude that large increase in serum non-esterified EPA and DHA, which can only be attained by supplementation, might increase inflammation in vascular endothelium. A moderate dietary increase in fish oil intake may, however, have an effect on decreasing inflammatory markers.