To Örebro University

INTRODUCTION: Platelet aggregation and secretion can be induced by a large number of endogenous activators, such as collagen, adenosine diphosphate (ADP) and epinephrine. Conversely, the blood vessel endothelium constitutively release platelet inhibitors including nitric oxide (NO) and prostacyclin. NO and prostacyclin are also well-known vasodilators and contribute to alterations in local blood flow and systemic blood pressure.

MATERIALS AND METHODS: In this study we investigated individual variations in platelet reactivity and arterial functions including blood pressure and flow-mediated vasodilation (FMD) in 43 young, healthy individuals participating in the Lifestyle, Biomarkers and Atherosclerosis (LBA) study. Platelet aggregation and dense granule secretion were measured simultaneously by light transmission and luminescence. FMD was measured with ultrasound.

RESULTS: The platelet function assay showed inter-individual differences in platelet reactivity. Specifically, a sub-group of individuals had platelets with an increased response to low concentrations of ADP and epinephrine, but not collagen. When the NO-donor S-nitroso-N-acetyl-DL-penicillamine (SNAP) was combined with high doses of these platelet activators, the results indicated for sub-groups of NO-sensitive and NO-insensitive platelets. The individuals with NO-sensitive platelets in response to SNAP in combination with collagen had a higher capacity of FMD of the arteria brachialis.

CONCLUSIONS: Platelet reactivity towards ADP, epinephrine and NO differs between young, healthy individuals. Some individuals have a more effective response towards NO, both in the aspect of platelet inhibition ex vivo, as well as vasodilation in vivo.

Background: The progression of cardiovascular disease (CVD) and atherosclerosis is slow and develops over decades. In the cross-sectional Swedish Lifestyle, Biomarker, and Atherosclerosis study, 834 young, self-reported healthy adults aged 18.0-25.9 years have been studied to identify early risk factors for atherosclerosis.

Purpose: The aims of this study were to 1) assess selected cardiometabolic biomarkers, carotid intima-media thickness (cIMT) as a marker of subclinical atherosclerosis, and lifestyle-related indicators (food habits, handgrip strength, and oxygen uptake, VO(2)max);2) analyze the associations between cIMT and lifestyle factors; and 3) identify subjects at risk of CVD using a risk score and to compare the characteristics of subjects with and without risk of CVD.

Method: Blood samples were taken in a fasting state, and food habits were reported through a questionnaire. cIMT was measured by ultrasound, and VO2 max was measured by ergometer bike test. The risk score was calculated according to Wildman.

Result: cIMT (mean +/- standard deviation) was 0.50 +/- 0.06 mm, and VO2 max values were 37.8 +/- 8.5 and 42.9 +/- 9.9 mL/kg/min, in women and men, respectively. No correlation was found between aerobic fitness expressed as VO2 max (mL/kg/min) and cIMT. Using Wildman's definition, 12% of the subjects were classified as being at risk of CVD, and 15% had homeostasis model assessment of insulin resistance. A total of 35% of women and 25% of men had lower high-density lipoprotein cholesterol than recommended. Food habits did not differ between those at risk and those not at risk. However, aerobic fitness measured as VO2 max (mL/kg/min) differed; 47% of the subjects at risk had low aerobic fitness compared to 23% of the nonrisk subjects (P<0.001).

Conclusion: High aerobic fitness is associated with low CVD risk in Swedish young adults. The high prevalence of young adults observed with unfavorable levels of high-density lipoprotein cholesterol and homeostasis model assessment of insulin resistance raises concerns about future CVD risk.

Background: Early changes in the large muscular arteries are already associated with risk factors as hypertension and obesity in adolescence and young adulthood. The present study examines the association between arterial stiffness measurements, pulse wave velocity and augmentation index and lifestyle-related factors, body composition and cardiorespiratory fitness, in young, healthy, Swedish adults.

Design: This study used a population-based cross-sectional sample.

Methods: The 834 participants in the study were self-reported healthy, non-smoking, age 18-25 years. Augmentation index and pulse wave velocity were measured with applanation tonometry. Cardiorespiratory fitness was measured by ergometer bike test to estimate maximal oxygen uptake. Body mass index (kg/m(2)) was calculated and categorised according to classification by the World Health Organisation.

Results: Young Swedish adults with obesity and low cardiorespiratory fitness have significantly higher pulse wave velocity and augmentation index than non-obese young adults with medium or high cardiorespiratory fitness. The observed U-shaped association between pulse wave velocity and body mass index categories in women indicates that it might be more beneficial to be normal weight than underweight when assessing the arterial stiffness with pulse wave velocity. The highest mean pulse wave velocity was found in overweight/obese individuals with low cardiorespiratory fitness. The lowest mean pulse wave velocity was found in normal weight individuals with high cardiorespiratory fitness. Cardiorespiratory fitness had a stronger effect than body mass index on arterial stiffness in multiple regression analyses.

Conclusions: The inverse association between cardiorespiratory fitness and arterial stiffness is observed already in young adults. The study result highlights the importance of high cardiorespiratory fitness, but also that underweight individuals may be a possible risk group that needs to be further studied.

Background: Weight loss resulting from low-calorie diets is often less than expected. We hypothesized that energy restriction would influence proton leakage and improve mitochondrial efficiency, leading to reduced energy expenditure, partly explaining the difficulties in weight loss maintenance.

Methods: Eleven women with a median BMI of 38.5 kg/m(2) (q-range 37-40), and referred to gastric bypass surgery participated. Before surgery, and at 6 months of follow-up, muscle biopsies were collected from the vastus lateralis muscle. Mitochondria were isolated and analyzed for coupled (state 3) and uncoupled (state 4) respiration and mitochondrial capacity (P/O ratio).

Results: At follow-up, the participants had a median BMI of 29.6 kg/m(2) (28.3-32.0). State 3 increased from 20.6 (17.9-28.9) to 34.9 nmol O2/min/U citrate synthase (CS) (27.0-49.0), p = 0.01, while state 4 increased from 2.8 (1.8-4.2) to 4.2 nmol O2/min/U CS (3.1-6.1), although not statistically significant. The P/O ratio increased from 2.7 (2.5-2.8) to 3.2 (3.0-3.4), p = 0.02, indicating improved mitochondrial efficiency.

Conclusions: Six months after gastric bypass surgery, the mitochondrial capacity for coupled, i.e., ATP-generating, respiration increased, and the P/O ratio improved. Uncoupled respiration was not enhanced to the same extent. This could partly explain the decreased basal metabolism and the reduced inclination for weight loss during energy restriction.