Summary. Background: Platelet size, measured as mean platelet volume (MPV), is associated with platelet reactivity. MPV is increased in acute myocardial infarction, and has been identified as an independent risk factor for future myocardial infarction and stroke. Objectives: The purpose of the study was to determine the impact of platelet count and MPV on the incidence of venous thromboembolism (VTE) in a prospective, population-based study. Methods: Platelet count, MPV and baseline characteristics were registered in 25 923 subjects aged 25-96 years who participated in the Tromsø Study in 1994-1995. Incident VTE events were registered to the end of followup (1 September 2007). Results: There were 445 validated incident VTE events (1.6 per 1000 person-years), of which 186 (42%) were unprovoked, during a mean of 10.8 years of followup. Subjects with MPV ‡ 9.5 fL had a 1.3-fold [95% confidence interval (CI) 1.0-1.7] higher risk of total VTE and a 1.5-fold (95% CI 1.1-2.3) higher risk of unprovoked VTE than subjects with MPV < 8.5 fL in analyses adjusted for age, sex, smoking, body mass index, and platelet count. Increasing MPV was associated with increased risk of total VTE (P for trend = 0.09) and unprovoked VTE (P for trend = 0.03) in analyses adjusted for age and sex. There was no significant association between increasing platelet count and risk of VTE. Conclusions: An increasing MPV was identified as a predictor for VTE, in particular VTE of unprovoked origin. The present findings support the concept that platelet reactivity is important in the pathogenesis of VTE.

To compare the effects of highly purified ethyl ester concentrates of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on serum lipids, apolipoproteins, and serum phospholipid fatty acids in humans, we conducted a double-blind, placebo-controlled, parallel design intervention study. Healthy nonsmoking men (n = 234) aged 36-56 y were randomly assigned to dietary supplementation with 3.8 g EPA/d, 3.6 g DHA/d, or 4.0 g corn oil/d (placebo) for 7 wk. Serum triacylglycerols decreased 26% (P < 0.0001) in the DHA group and 21% (P = 0.0001) in the EPA group compared with the corn oil group. Although not significant, net decreases in serum triacylglycerols were consistently greater in the DHA group across all quartiles of baseline triacylglycerol concentrations. Serum high-density-lipoprotein cholesterol increased 0.06 mmol/L (P = 0.0002) in the DHA group. In the EPA group, serum total cholesterol decreased 0.15 mmol/L (P = 0.02) and apolipoprotein A-I decreased 0.04 g/L (P = 0.0003). In the DHA group, serum phospholipid DHA increased by 69% and EPA increased by 29%, indicating retroconversion of DHA to EPA. In the EPA group, serum phospholipid EPA increased by 297% whereas DHA decreased by 15%, suggesting that EPA is not elongated to DHA in humans. The serum phospholipid ratio of n-3 to n-6 fatty acids increased in both groups, whereas the relative changes in n-6 fatty acids suggested possible alterations in liver desaturation activity in the DHA group. We conclude that both DHA and EPA decrease serum triacylglycerols, but have differential effects on lipoprotein and fatty acid metabolism in humans.

An association between body height and venous thromboembolism (VTE) has been suggested by previous studies including males only. The aim of this prospective cohort study was to investigate the sex-specific impact of body height on risk of VTE in a general population. Risk factors, including body height and weight, were registered for 26,727 subjects aged 25-96 years who participated in the Tromsø Study (Norway) in 1994-1995. Incident VTE events were registered through September 1, 2007. There were 462 VTE events during a median 12.5 years of follow-up. Body height was a risk factor for VTE in men, but not in women. Multivariable hazard ratios per 10 cm, adjusted for age, body mass index, diabetes, smoking, and hormone therapy (women), were 1.34 (95% confidence interval: 1.09, 1.64) for men and 1.13 (95% confidence interval: 0.91, 1.40) for women. Hazard ratios by quartiles of body height revealed that men in the upper quartile (>181 cm) had a 1.99-fold (95% confidence interval: 1.35, 2.92) increased risk of VTE compared with men in the lowest quartile (<173 cm) (P for trend across quartiles = 0.002). There was no significant trend (P = 0.2) across quartiles of body height for women. Study findings revealed that body height is a sex-specific risk factor for VTE in men.

The hemodynamic effects of highly purified eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) have not been evaluated in humans. We therefore conducted a randomized, double-blind, parallel-design intervention study to assess possible separate effects of EPA and DHA on blood pressure, heart rate, and cardiac mechanics. Healthy, nonsmoking men aged 36-56 y (n = 224) were randomly assigned to dietary supplementation with 4 g/d of ethyl ester concentrates of DHA or EPA or 4 g corn oil/d (control). Mean blood pressure at baseline was 122/77 mm Hg and was positively associated with concentrations of serum phospholipid saturated fatty acids. Blood pressure did not change during the intervention. Mean heart rate at baseline was 63.4 beats/min; it decreased 2.2 beats/min in the DHA group (P = 0.006 compared with control), increased 1.9 beats/min in the EPA group (P = 0.04 compared with control), and remained practically unchanged in the control group. In a pooled analysis, changes in heart rate were independent of baseline heart rate and were associated with changes in concentrations of serum phospholipid DHA and docosapentaenoic acid (22:5n-3). Echocardiography in a subsample of 52 men showed improved left ventricular diastolic filling in the marine oil groups compared with the corn oil group (P = 0.02). In contrast, an increase in plasma concentrations of saturated fatty acids was associated with delayed diastolic filling. We conclude that dietary DHA and EPA influence heart rate and that the fatty acid composition of plasma phospholipids may affect cardiac mechanics in humans.

BackgroundHematocrit above the normal range for the population, such as in primary or secondary erythrocytosis, predisposes to both arterial and venous thrombosis. However, little is known about the association between hematocrit and risk of venous thromboembolism in a general population. Design and MethodsHematocrit and related hematologic variables such as hemoglobin, red blood cell count, mean corpuscular volume, and baseline characteristics were measured in 26,108 subjects, who participated in the Tromsø Study in 1994-1995. Incident venous thromboembolic events during follow-up were registered up to September 1 st , 2007. ResultsThere were 447 venous thromboembolic events during a median of 12.5 years of followup. Multivariable hazard ratios per 5% increment of hematocrit for the total population, adjusted for age, body mass index and smoking, were 1.25 (95% CI: 1.08-1.44) for total venous thromboembolism and 1.37 (95% CI: 1.10-1.71) for unprovoked venous thromboembolism. In category-based analyses, men with a hematocrit in the upper 20 th percentile (≥46% in men) had a 1.5-fold increased risk of total venous thromboembolism (95% CI: 1.08-2.21) and a 2.4-fold increased risk of unprovoked venous thromboembolism (95% CI: 1.36-4.15) compared to men whose hematocrit was in the lower 40 th percentile. The risk estimates were higher for men than for women both in continuous and category-based analyses. The findings for hemoglobin and red blood cell count were similar to those for hematocrit, whereas mean corpuscular volume was not associated with venous thromboembolism. ConclusionsOur findings suggest that hematocrit and related hematologic variables such as hemoglobin and red blood cell count are risk factors for venous thromboembolism in a general population.Key words: hematocrit, population range, arterial and venous thrombosis. Study. Haematologica. 2010; 95:270-275. doi:10.3324/haematol.2009 Hematocrit and risk of venous thromboembolism in a general population. The Tromsø study Citation: Braekkan SK, Mathiesen EB, Njølstad I, Wilsgaard T, and Hansen J-B. Hematocrit and risk of venous thromboembolism in a general population. The Tromsø