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Blood pressure (BP) levels in the Finnish population are amongst the highest in the world, despite favourable changes at the national level in the past two ...
Journal of Human Hypertension (2000) 14, 441–445  2000 Macmillan Publishers Ltd All rights reserved 0950-9240/00 $15.00 www.nature.com/jhh

ORIGINAL ARTICLE

Familial aggregation of blood pressure: a population-based family study in eastern Finland RM Fuentes1, I-L Notkola1, S Shemeikka1, J Tuomilehto2 and A Nissinen1,3 1

Department of Public Health and General Practice, Faculty of Medicine, University of Kuopio, Kuopio, Finland; 2Diabetes and Genetic Epidemiology Unit, Department of Epidemiology and Health Promotion, National Public Health Institute, Helsinki, Finland; 3Department of Neurology, Faculty of Medicine, University of Kuopio, Kuopio, Finland

Blood pressure (BP) levels in the Finnish population are amongst the highest in the world, despite favourable changes at the national level in the past two decades. The study evaluates the familial aggregation of BP and the association of some environmental factors to the familial aggregation of BP as a primary epidemiological approach of the genetics of hypertension in a sample of families with young offspring from eastern Finland. Offspring aged 15 years were examined between 1996 and 1997 and their biological parents were examined between 1993 and 1994. A total of 224 children were invited, 184 families participated, from which 144 were included in the analysis with complete data. Systolic (SBP), diastolic (DBP) and mean (MAP) arterial BPs were the main outcome measurements. After the offspring’s gender and body mass index (BMI) and the parent’s age

and BMI were controlled for, the mother/offspring correlation of SBP and the father/offspring correlation of MAP were statistically significant (r ⴝ 0.18, P ⴝ 0.039, n ⴝ 134 and r ⴝ 0.20, P ⴝ 0.048, n ⴝ 99, respectively). The additional adjustment for the parent’s education and family history of acute myocardial infarction did not change these results. There was a higher proportion of offspring in the highest quartile of SBP and MAP when the mother had a history of hypertension (OR ⴝ 3.4, 95% CI ⴝ 1.4 –8.5, n ⴝ 139, and OR ⴝ 2.6, 95% CI ⴝ 1.0–6.5, n ⴝ 139, respectively). The study confirmed the familial aggregation of BP. The consistent BP association between the mother and the offspring may indicate the key role of the mother in the primary prevention of hypertension. Journal of Human Hypertension (2000) 14, 441–445

Keywords: familial aggregation; children; blood pressure; correlation

Introduction Arterial blood pressure (BP) has been found to be predictive of stroke, coronary heart disease (CHD), heart failure, renal disease and peripheral arterial disease.1–5 In the past two decades the coronary mortality in eastern Finland has halved,6,7 approximately half of that decline was associated with positive changes in smoking, serum cholesterol and BP.3 However, according to the WHO MONICA Project, BP levels in the Finnish population are amongst the highest in the world.8 In the North Karelia province between 1982 and 1997 the age-adjusted prevalence of hypertension in the adult population (BP ⭓160/95 mm Hg or under antihypertensive drug treatment) has decreased from 31% to 25% in men and from 24% to 17% in women. Although there are regional differences in trends of hypertension prevalence in Finland, these advantageous trends have Correspondence: Dr Ricardo Fuentes, Department of Public Health and General Practice, University of Kuopio, P.O.B. 1627, FIN-70211 Kuopio, Finland E-mail: ricardo.fuentes얀messi.uku.fi Received 1 February 2000; revised 20 March 2000; accepted 7 April 2000

been the result of favourable changes on lifestyles at the population level.9 The high level of BP in the Finnish population in international comparisons, which has persisted even after favourable changes at the national level, suggests that genetics may play an important causal role on the development of hypertension in the Finnish population. It has been estimated that approximately 30% of population variability of BP is accounted for by genetic heritability and that 60–70% of the familial aggregation of BP is ultimately due to genetic background.10 Finland, with its high cardiovascular disease (CVD) morbidity and mortality, high BP levels, and relatively homogeneous population,11 is well suited for family studies aimed at evaluating the genetic component of complex diseases such as CVD and related risk factors. The aims of this study were to investigate the familial aggregation of BP and to evaluate the association of some environmental factors to the familial aggregation of BP as a primary epidemiological approach of the genetics of hypertension in a sample of families with young offspring from eastern Finland. Our work hypotheses were that there is familial aggregation of BP in these families and that the association of BP between genetically related subjects (parents–offspring) is larger

Familial aggregation of blood pressure RM Fuentes et al

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than the association of BP between non-genetically related subjects (spouses).

Materials and methods The Project ‘From childhood to teenage years’ is a follow-up study on children’s development, health and life situation. It has consisted of periodical cross-sectional surveys of all children born between 1981 to 1982 living in a rural community in eastern Finland. For the present study the eligible population included 224 children born during 1981– 1982, living in the community at the age of 15 years (1996–1997). These children were contacted through the local primary schools. For this study the inclusion criteria were: (1) family positive informed consent (40 families did not give positive consent), (2) subjects with full data on BP (39 families in which the parents did not attend to the nurse session were excluded from the analysis), (3) parental relationship (one family in which the child was living with non-biological parents and nine stepfathers were excluded from the analysis). Altogether 144 children who participated at age 15 years and their parents (141 mothers and 127 fathers) who were evaluated at the survey at children’s age 12 years (1993–1994) were included in the analysis. Of the 144 index children 124 live with both biological parents, nine live with the biological mother and a stepfather (which was excluded from the analysis), eight live only with the biological mother and three live only with the biological father. Comprehensive health and lifestyle questionnaires were completed by the participants before physical measurements. Information on parenthood, parents’ education (years of school or full-time life studies), history of hypertension (ever been told having hypertension; yes, no), and family history of acute myocardial infarction (yes, at least one parent (grandparent of the index child) with history of acute myocardial infarction; no, no parent (grandparent of the index child) with history of acute myocardial infarction) was obtained by a selfadministered questionnaire. The physical measurements were conducted following the WHO MONICA Project standards.12 Weight was measured with subjects dressed in light indoor clothes without shoes using a digital scale with an accuracy of 0.1 kg. Height was measured by stadiometer of bare-footed subjects with an accuracy of 0.1 cm. Body mass index (BMI) was calculated as weight (kg) divided by the square of height (m). BP was measured on the right arm of subjects in a sitting position after 5 min of rest using a mercury sphygmomanometer with an accuracy of 2 mm Hg. Systolic BP (SBP) and diastolic BP (DBP) were recorded at the first and fifth phases of Korotkoff sounds, respectively. The mean of two measurements (separated by 3–5 min each) in parents and of three measurements (separated by 2 min each) in children was used in the study. Mean arterial BP (MAP) was calculated as 1/3SBP + 2/3DBP. T-test and ␹2 test were used to analyse differences between groups in continuous and categorical variables. Linear regression model was used to adjust Journal of Human Hypertension

BP values for the child’s gender and BMI, and the parent’s age, education, BMI, and family history of acute myocardial infarction. The regression-unstandardised residual was used as the adjusted BP in the analysis. Familial aggregation was investigated by two statistical methods. Firstly, Pearson correlations of BP were calculated between the family members without and with adjustment for confounding variables. Thirteen parents (five mothers and eight fathers) who were under antihypertensive drug treatment were excluded from the correlation analysis of quantitative traits. Since families with a member who had had myocardial infarction could consequently have changed their lifestyle patterns, like diet and physical activity, family history of acute myocardial infarction was included as a control variable in this analysis. Secondly, the child’s odds of being in the highest quartile of the gender-specific BP distribution was studied according to the parental history of hypertension. Parental history of hypertension was used in this analysis because it has been made by a physician on the basis of BP measurements taken at least on three subsequent occasions, which is more reliable than hypertension based on casual BP measurements. Results were considered as statistically significant with P-value ⬍0.05. All the statistical analyses were carried out using the SPSS program.

Results Fathers were older, and had lower education, higher BMI and BP than mothers (Table 1). A higher proportion of fathers had history of hypertension and family history of acute myocardial infarction than mothers. Boys had higher SBP than girls. No gender differences were found in other BP parameters and BMI among children. Children had lower levels of BP and BMI than their parents. Familial correlations of blood pressure The lowest familial correlations of BP were found of DBP, which were not statistically significant (Table 2). The correlations of BP between spouses were only a little lower than the parent–offspring correlations of BP, but they were not statistically significant. After controlling for the offspring’s gender and BMI and the parent’s age and BMI the mother/offspring correlation of SBP and the father/offspring correlation of MAP were statistically significant. No statistically significant gender differences in the familial correlations of BP were found. The additional adjustment for the parent’s education and family history of acute myocardial infarction did not change these results. BP level of the offspring according to the history of hypertension of the parents There was a higher proportion of offspring in the highest quartile of SBP and MAP in families where the mother had history of hypertension (Table 3). The offspring of mothers with history of hyperten-

Familial aggregation of blood pressure RM Fuentes et al

Table 1 Blood pressure and other selected variables among 144 index children and their biological parentsa Variable

Parents

P-value

443

Table 2 Familial correlations of blood pressure Familial membership

No.

Pearson Correlation Model 1 Model 2 Model 3

Mothers (n = 135)

Age (years) Education (years) BMI (kg/m2) DBP (mm Hg) SBP (mm Hg) MAP (mm Hg)

History of HTb Family history of AMIb

mean

s.d.

mean

s.d.

38.8 11.4 25.8 77.1 128.7 94.3

5.2 2.9 3.7 11.0 13.6 10.9

41.7 10.3 26.8 81.6 137.7 100.3

5.4 3.2 3.3 10.6 15.0 10.8

0.000 0.008 0.033 0.002 0.000 0.000

%

n

%

n

P-value

14 34

133 129

30 50

98 96

0.005 0.016

Variable

BMI (kg/m2) DBP (mm Hg) SBP (mm Hg) MAP (mm Hg)

Fathers (n = 101)

Children

P-value

Girls (n = 65)

Boys (n = 79)

mean

s.d.

mean

s.d.

21.9 63.7 114.6 80.7

4.0 9.3 9.8 7.7

21.1 60.6 120.7 80.7

2.9 10.3 9.9 8.8

0.173 0.064 0.000 0.985

a

Only data of parents with complete anthropometric and BP measurements are included. b The number of subjects may vary according to missing values. BMI, body mass index; DBP, diastolic blood pressure; SBP, systolic blood pressure; MAP, mean arterial pressure; History of HT, history of hypertension. Family history of AMI, parental history of acute myocardial infarction—No, no parent with AMI; Yes, at least one parent with AMI.

sion compared with the offspring of mothers without history of hypertension had 3.4-fold and 2.6-fold higher odds to be in the highest quartile of their gender-specific SBP and MAP distributions, respectively. The father’s history of hypertension was not significantly associated with the level of BP of the offspring.

Discussion The spouse correlations of BP, although not statistically significant, were only a little lower than the parent–offspring correlations of BP. Assortative marriage and cohabitation have been suggested as the main factors contributing to the spouse concordance of BP, but they were not analysed in this study.13–16 The parent–offspring correlations of BP were significant for the mother/offspring correlation of SBP and the father/offspring correlation of MAP. Both genetic and environmental factors may explain the concordance of BP between the parents and the offspring. We did not find gender differences in the familial correlations of BP. After the effect of BMI was accounted for the gender differences in the crude familial correlations of BP tended to disappear, despite significant positive correlations of BMI between the mother and the offspring (r = 0.31, P ⬍

DBP Spouses Mother/offspring Father/offspring Mother/daughter Mother/son Father/daughter Father/son

93 134 99 60 74 42 57

0.14 0.07 0.08 0.13 0.03 0.03 0.10

0.08 0.06 0.09 0.09 0.05 0.03 0.13

0.06 0.08 0.14 0.08 0.08 0.11 0.16

SBP Spouses Mother/offspring Father/offspring Mother/daughter Mother/son Father/daughter Father/son

93 134 99 60 74 42 57

0.09 0.23* 0.17 0.28* 0.16 0.11 0.15

0.13 0.18* 0.11 0.23 0.13 0.12 0.12

0.16 0.18* 0.15 0.18 0.17 0.21 0.11

MAP Spouses Mother/offspring Father/offspring Mother/daughter Mother/son Father/daughter Father/son

93 134 99 60 74 42 57

0.15 0.16 0.17 0.26* 0.08 0.09 0.23

0.11 0.13 0.17 0.19 0.09 0.10 0.23

0.13 0.14 0.20* 0.16 0.13 0.18 0.23

DBP, diastolic blood pressure; SBP, systolic blood pressure; MAP, mean arterial blood pressure; No., number of pairs. Model 1, no adjustments; Model 2, BP of the parents adjusted for age/ BP of the offspring adjusted for gender (when appropriate); Model 3, BP of the parents adjusted for age and BMI/BP of the offspring adjusted for BMI and gender (when appropriate). * Two-tail P-value ⬍0.05.

0.001, n = 140), and the father and the offspring (r = 0.23, P = 0.017, n = 107) in the same sample (results not shown). Sexual dimorphism during adolescence is reflected, among others, in different patterns of adiposity deposition and muscle development between girls and boys, and this may explain gender differences of crude familial correlations of BP. It has been described that within a family adiposity and BP share some of the same genetic components,17,18 and this has been the reason why some authors did not adjust the familial correlations of BP for BMI. In our study we adjusted the familial correlations of BP for BMI, after which the mother/offspring correlation of SBP tended to decrease but remained significant and the father/offspring correlation of MAP tended to increase and became statistically significant. These findings suggest an effect of adiposity on the familial correlations of BP. They also suggest that there are genetic and environmental factors for the familial correlations of BP not related with adiposity. The levels of the familial correlations of SBP were similar to those reported before. Pe´russe et al19 in a non-random sample of 304 French descent families living in Quebec, Canada, found correlations of SBP of 0.17 between spouses, 0.25 between the mother and the offspring and 0.20 between the father and the offspring, all of them statistically significant. Fossali et al20 in a random sample of 477 schoolage children and their parents living in Milan, Italy, Journal of Human Hypertension

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Table 3 Blood pressure of the offspring according to history of hypertension in parents Parental history of hypertension

Blood pressure of the offspring DBP

Mother Yes No OR (95%Cl); P-value n Father Yes No OR (95% CI); P-value n

SBP

MAP

High

Low

High

Low

High

Low

8 30

16 85

12 26

12 89

10 25

14 90

1.42 (0.55–3.65); 0.47 139 11 21

28 56

1.05 (0.44 –2.47); 0.92 116

3.42 (1.38–8.51); 0.01 139 11 22

28 55

0.98 (0.42–2.31); 0.97 116

2.57 (1.02–6.48); 0.04 139 9 20

30 57

0.86 (0.35–2.11); 0.74 116

DBP, diastolic blood pressure; SBP, systolic blood pressure; MAP, mean arterial blood pressure; High, BP equal or higher than the gender-specific percentile 75th; Low, BP lower than the gender-specific percentile 75th; OR, Odds Ratio; 95% CI, 95% confidence interval; n, number of pairs.

found correlations of SBP of 0.16 between the mother and the offspring, and 0.13 between the father and the offspring, both of them were also statistically significant. Tienboon et al21 in a non-random sample of 213 families with adolescent offspring from Geelong, Victoria, Australia, found correlations of SBP of 0.002 between spouses, 0.197 between the mother and the offspring and 0.238 between the father and the offspring, the last two were statistically significant. The low levels of the familial correlations of DBP may be related to the reliability of the measurement of DBP, which is lower than for SBP. Berenson,22 in a sample of 3.524 children aged 5–14 years, studied the reliability of fourth and fifth Korotkoff phases as indirect methods to measure DBP. He found that the fifth phase measurement had less consistency and replicability than the fourth phase measurement. The opposite was found by Uhari et al23 in a 6-year follow-up survey of 2.500 children aged 6–18 years. They found that the fifth phase measurement of DBP was more reliable and repeatable than the fourth phase measurement in all age groups. The significant association of the mother’s history of hypertension with the offspring’s level of SBP and MAP is in keeping with results reported by others, but the lack of association of the father’s history of hypertension with the level of BP of the offspring is not.24–26 The categorisation of the subjects in highlow BP groups is arbitrary, and it can affect the association we are looking for. After the application of the inclusion criteria a lower number of fathers than mothers were included in the analysis which also could have affected the association of BP between the parents and the offspring. In our study the parents were relatively young and some of those without history of hypertension are likely to develop high BP levels later on in their life, which possibly has an effect on the prevalence of parental history of hypertension. Maternal factors that may explain the concordance of BP between the mother Journal of Human Hypertension

and the offspring include maternal sociodemographic factors and intrauterine conditions during pregnancy that predispose the child to develop high BP later on in life.27–31 Also the capability of the mother in influencing the nutritional intakes of the child during childhood, especially in relation to BPrelated dietary factors, and in supporting the participation of the child in physical activities may play a role. Familial aggregation of nutrient intake and physical activity has been reported, and few studies have found a stronger association of these CVD risk factors between the mother and the offspring.32–37 In conclusion our study has also confirmed a significant familial aggregation of BP in Finnish families with young offspring. We found statistically significant positive parent/offspring correlations of BP and a significant association between the level of BP of the offspring and the history of hypertension of the mother. This may indicate the key role of the mother in the primary prevention of hypertension, particularly in high-risk families.

Acknowledgements This study was funded by the Juho Vainio Foundation, the Finnish Cultural Foundation of Northern Savo, the Ministry of Education of Finland and the Academy of Finland.

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