Laura Jartti

Population-Based Twin Study of the Effects of Migration From Finland to Sweden on Endothelial Function and Intima-Media Thickness

Finnish men have higher coronary heart disease (CHD) mortality than Swedish men do. To assess the impact of migration to a country with lower CHD mortality on subclinical atherosclerosis, we measured early functional and structural atherosclerotic vascular changes in twins discordant for migration from Finland to Sweden. Conventional CHD risk factors, flow-mediated dilatation (FMD) of the brachial artery, carotid intima-media thickness, and carotid artery compliance were measured in 74 male twin pairs (20 monozygous, 54 dizygous), aged 42 to 69 years, in which co-one twin had migrated more than 20 years ago permanently to Sweden. There were no significant differences in CHD risk factors except for diastolic blood pressure and body fat percentage, which were higher in Sweden. In all subjects, mean FMD was non-significantly higher in Sweden (5.7±4.3% vs 4.9±4.2%, P =0.22), but in monozygous twins the difference in FMD was highly significant (7.2±4.4 vs 3.7±2.9%, P =0.003). There was no significant difference in intima-media thickness or carotid artery compliance between Sweden and Finland. We conclude that in Finnish monozygous twins the endothelial function is better among the twins that have migrated to a country with lower CHD prevalence.

Determinants of short-term variation in arterial flow-mediated dilatation in healthy young men

Brachial artery FMD (flow-mediated dilatation) is widely used as a marker of systemic arterial endothelial function. FMD, however, shows considerable 25% day-to-day variation that hinders its clinical use. The reasons for this variability are poorly characterized. Therefore the present study was designed to clarify factors responsible for the hourly variation in endothelial function, including consuming a low-fat meal and circadian rhythms in endogenous hormonal levels. Brachial artery FMD, along with serum glucose, triacylglycerols (triglycerides) and levels of several hormones were measured six times per day on two separate days 1 week apart. On one day, the subjects (healthy males: n=12, mean age, 24 years) ate a light breakfast and a standardized lunch (23.5% fat, 48.7% carbohydrate and 27.8% protein). On the other day, they had a similar breakfast after which they fasted. Postprandial FMD values (both after breakfast and after lunch) were similar to baseline FMD. FMD showed a 28% hourly variation and 27% weekly variation. Variation in plasma levels of insulin (P=0.02) associated negatively and DHPG (3,4-dihydroxyphenylglycol) (P=0.001), a marker of sympathetic nervous activation, associated positively with variation in FMD. The effects of DHPG and insulin on FMD were independent of changes in baseline brachial artery diameter, although DHPG was also inversely associated with baseline diameter. Eating a regular low-fat meal does not have any measurable effects on brachial artery endothelial function. These data suggest that strict requirements for fasting conditions may be unnecessary when measuring peripheral endothelial function using the ultrasound technique. Circadian variation in serum insulin and sympathetic tone are physiological determinants of endothelial function.

Enhanced endothelium-dependent vasodilation in subjects with Proline7 substitution in the signal peptide of neuropeptide Y

Neuropeptide Y (NPY) is a molecule that may have both vasoconstrictive and vasodilatory actions. A common polymorphism in the human NPY gene that results in the Leucine7 to Proline7 substitution (Leu7Pro) in the signal peptide part of the NPY was recently identified. This substitution has been associated with elevated serum cholesterol levels and with slightly accelerated progression rate of carotid intima-media thickness, thus suggesting increased risk of atherosclerosis in carriers of Pro7 substitution. Recent data also indicate that subjects with Pro7 substitution may have increased endothelial release of NPY. This study was undertaken to elucidate the effects of Leu7Pro polymorphism on arterial endothelial function. We measured flow-mediated endothelial-dependent dilatation (FMD) of the brachial artery in two separate populations: in 152 middle-aged men and in 95 prepubertal children. In both study populations, subjects with Pro7 substitution had 48-52% higher FMD compared with subjects having the wildtype (Leu7/Leu7) signal peptide sequence. We conclude that Pro7 substitution in signal peptide of the NPY is associated with enhanced endothelial-dependent vasodilation. Prospective studies are needed to determine whether Pro7 substitution is associated with increased or decreased risk of cardiovascular morbidity and mortality.

Noninvasive assessment of brachial artery endothelial function with digital ultrasound and 13-MHz scanning frequency: feasibility of measuring the true inner luminal diameter using the intima-lumen interface

Previous studies assessing endothelial function as flow-mediated changes in the brachial artery diameter have not been able to measure the true inner luminal diameter. This is due to the lack of image quality, which has hampered the visualisation of the lumen-intimal interface. Because increases in resolution and scanning frequency have recently led to improved ultrasound (US) image quality, we assessed the feasibility of measuring the true brachial artery diameter using digital US and 13-MHz scanning frequency. Satisfactory true inner diameter measurements were obtained in all subjects (n = 148, middle-aged men, mean age 54 +/- 7 y) participating in a risk factor study. At baseline flow, the intima to intima diameter was 4.03 +/- 0.49 and 4.67 +/- 0.52 mm measured conventionally from the anterior to the posterior media-adventitia interface (difference 0.64 +/- 0.10 mm). After hyperaemia, the intima to intima diameter was 4.23 +/- 0.46 mm and the adventitia to adventitia diameter 4.86 +/- 0.50 mm. Flow-mediated dilation (FMD) expressed as the percentage change from the baseline diameter measured 5.3 +/- 4.3% using the true inner diameters and 4.3 +/- 3.7% using the conventional outer diameters. The difference in FMD values was systematic, and there was a good linear correlation between them (r = 0.93, p < 0.0001). If FMD is presented as the percentage change from baseline to hyperaemia, this new method gives values that are approximately 1% unit higher, compared with values when brachial luminal diameter is measured in the conventional way between the adventitia-media interfaces.

Increased carotid intima-media thickness in men born in east Finland: a twin study of the effects of birthplace and migration to Sweden on subclinical atherosclerosis

BACKGROUND. There is a clear east-west difference in coronary heart disease (CHD) mortality and incidence in Finland, people living in east Finland having higher CHD rate. A study of Finnish immigrants to Sweden has suggested that a long stay in Sweden would be associated with reduced CHD risk. AIM. To determine whether structural and functional markers of subclinical atherosclerosis differ between men originating from east and west Finland, and whether migration to Sweden influences subclinical atherosclerosis. METHOD. Carotid intima-media thickness (IMT) and brachial artery flow-mediated dilatation (FMD) with high-resolution ultrasound and a set of cardiovascular risk factors were measured in 76 middle-aged male twin pairs (55 pairs from east and 21 pairs from west Finland) discordant for migration to Sweden. RESULTS. Among men living in Finland, IMT was significantly higher in men originating from east Finland compared to those from west Finland (0.796 - 0.212 versus 0.704 - 0.123 mm, P = 0.02). A similar east-west difference was observed in men who had migrated to Sweden (0.766 - 0.220 versus 0.686 - 0.089 mm, P = 0.03). The east-west difference in IMT persisted after adjustment for the major traditional cardiovascular risk factors. No east-west difference was seen in FMD. Smoking, Framingham risk score and physical activity had a greater impact on IMT in men originating from east compared to west Finland. CONCLUSIONS. Men originating from east Finland, irrespective of their current residence, have a greater degree of subclinical atherosclerosis and they may be more susceptible to the impact of conventional cardiovascular risk factors than men originating from west Finland.

Migration and coronary heart disease: A study of Finnish twins living in Sweden and their co-twins residing in Finland.

Background: Finland and Sweden are neighbouring countries with a substantially higher incidence and mortality from coronary heart disease (CHD) in Finland. Migration from Finland to Sweden has resulted in a population of about 187,000 Finnish immigrants, with a higher risk of CHD than Swedes. The aim of the present study was to analyse the prevalence of CHD in migrants to Sweden compared with co-twins remaining in Finland. Methods: The study population consisted of twin pairs of the Finnish Twin Cohort Study where at least one twin had lived one year or more in Sweden, including 1,534 subjects and 251 complete twin pairs discordant regarding residency in Sweden. Emigrant twins were compared with non-migrant co-twins regarding prevalence of CHD in 1998. CHD prevalence was assessed by self-reported questionnaires validated using information from a clinical examination. Results: Self-reported CHD showed a good correspondence with clinical diagnosis. Differences in social and behavioural risk factors for CHD among men were small but emigrants were more physically active than non-migrants. Female emigrants had less overweight and better education, but were more often working class than non-migrants. Intra-pair comparisons restricted to migration discordant pairs showed a tendency towards a reduced prevalence of CHD in the migrant co-twins (0.6; 0.3—1.4). In analyses of all subjects disregarding pair status, emigrants showed a reduced prevalence of CHD compared with subjects always living in Finland (0.6; 0.4—0.9). Conclusion: Emigration from Finland to Sweden may be associated with a reduced prevalence of CHD. The causes are most likely multifactorial and may involve changes in dietary habits, physical activity, psychosocial factors, and inflammation.

Comparison of hand-to-leg and leg-to-leg bioelectric impedance devices in the assessment of body adiposity in prepubertal children. The STRIP study

The body composition of 40 seven‐year‐old children and of 50 of their parents was measured using two bioelectric impedance devices, the Model 101, RJL Systems, USA (conventional hand‐to‐leg device) and TANITA body fat analyser, TBF 105, Tanita Co, Tokio, Japan (newer leg‐to‐leg device). There were strong correlations between impedances obtained by these two devices [r= 0.95, r= 0.93, r= 0.82, r= 0.81 for girls (n= 22), boys (n= 18), mothers (n= 27) and fathers (n= 23), respectively (p < 0.0001 for all)]. However, there was a clear difference in the absolute impedance values due to the fact that the devices measure different segments of the body. Fat percentages based on inbuilt equations of the two devices correlated in girls, mothers and fathers (r= 0.71, r= 0.94, r= 0.80, respectively; p < 0.001) but not in boys (r= 0.21, p= 0.41). Using the Bland‐Altman comparison method, a large intraindividual difference was observed in the fat percentages by the two devices, independent of adiposity level. Both devices detected significant gender differences in fat percentages in 7‐y‐old girls and boys with similar BMIs.

Migration at early age from a high to a lower coronary heart disease risk country lowers the risk of subclinical atherosclerosis in middle-aged men

Background.  Study of migrants offers a natural model to assess environmental risk of coronary heart disease (CHD) in countries differing in CHD occurrence. In Sweden, CHD risk has been markedly lower than in Finland from where a large migration occurred in the 1970s.

Higher prevalence of Chlamydia pneumoniae seropositivity in Finnish twins compared with co-twins living in Sweden: relationships with markers of subclinical atherosclerosis

Mortality rates from coronary heart disease are lower in Swedish men and among Finnish migrants who have lived in Sweden for over 20 years than in men living in Finland. Sero-epidemiological studies, investigations of atheromatous plaque specimens, in vitro animal models and anti-chlamydial antibiotic trials have given support to the hypothesis that Chlamydia pneumoniae (Cpn) has a role in atherosclerosis. We investigated whether men with a similar genetic background but living permanently in Finland or Sweden have differences in the prevalence of Cpn seropositivity, and whether chronic Cpn infection is associated with markers of subclinical atherosclerosis. We measured anti-Cpn antibodies and ultrasonographic markers of subclinical atherosclerosis, including carotid intima-media thickness, carotid artery compliance and brachial artery flow-mediated dilatation, in a population of 76 migrant-discordant male twin pairs (152 men). The number of men with seropositivity to Cpn infection (defined as IgA>/=1:64 and IgG>/=1:128) was greater in Finland than in Sweden (21.5% compared with 10.5%; P =0.046). Cpn seropositivity accompanied by elevated C-reactive protein (CRP) levels (>1 mg/l) was associated with attenuated brachial artery flow-mediated dilatation (3.3+/-0.3%, compared with 5.5+/-0.4% in men with no signs of Cpn infection; P <0.001).Thus, among Finnish twin brothers discordant for migration to Sweden, the prevalence of Cpn seropositivity is higher for those living in Finland, and men with Cpn seropositivity combined with elevated CRP levels had attenuated endothelial function. These findings offer insight into the mechanism whereby chronic Cpn infection may increase the risk of coronary heart disease.