Do siblings of myocardial infarction patients have a specific management of hypertension?

Abstract

The aim of this study was to determine whether the management of hypertension differs between siblings of myocardial infarction patients and the general population. Siblings aged 35 to 74 years, unaffected by myocardial infarction, were drawn from the Augsburg Family Heart Study, conducted in 1996–1997 in southern Germany (n = 524). The reference group consisted of participants of the third MONICA population-based survey conducted in 1994–1995 in the same area, who were aged 35 to 74 years and also unaffected by myocardial infarction (n = 3802). Prevalence, awareness, treatment and control of hypertension (defined by blood pressure 140/90 mm Hg or use of antihypertensive medication) were compared between the two groups. The result was that the prevalence of hypertension was higher in the siblings (men: age-adjusted OR = 1.31, 95% CI: 0.99–1.75; women: age-adjusted OR = 1.83, 95% CI: 1.39–2.41). Male hypertensive siblings were more often aware and treated for hypertension than male hypertensives of the reference group whereas the level of awareness and treatment was comparable between female hypertensives of the two groups. In both genders, no difference in the degree of control was shown between hypertensives of the two groups. In conclusion the siblings and their physicians should pay more attention to the family history of myocardial infarction in order to improve the management of hypertension in this high risk group.

Introduction

Family history of coronary heart disease is an independent risk factor for coronary heart disease.1,2 The magnitude of this risk varies with different parameters such as age at which the event occurred,2,3 sex,3,4 and number of affected first-degree relatives.2,3 For example, Roncaglioni et al2 showed that the relative risk of myocardial infarction was 2.0 in those with one, and 3.0 in those with two or more first-degree relatives affected compared with those without a family history of myocardial infarction.

The link between hypertension and the incidence of non-fatal and fatal myocardial infarction is also well known.5,6 In southern Germany, trends in cardiovascular risk factors were studied by the MONICA Augsburg Project with three independent cross-sectional population-based surveys during a 10-year observation period (1984–1995). Results showed that the mean values of systolic and diastolic blood pressure (SBP, DBP) remained practically unchanged in men and women7 even though the use of antihypertensive medication increased in hypertensives. In the last population survey (1994–1995), 74.5% of the men aged 25–64 years and 63.4% of the women of the same age group with hypertension (140/90 mm Hg) were untreated.8 Thus, a large effort is still to be made to improve the prevention and control of hypertension in the German population. Recently, the World Health Organization-International Society of Hypertension has published new recommendations for the management of hypertension.9 Decisions for treatment of patients with hypertension should not only be based on the level of blood pressure, but also on the presence of other risk factors such as positive family history of coronary heart disease. The aim of the present study is to determine whether the management of hypertensive siblings of myocardial infarction patients differs from the management of the general hypertensive population.

Materials and methods

Samples

Reference group:

The reference group consisted of the participants aged 35–74 years of the third population-based survey of the MONICA Augsburg Project (MONItoring of trends and determinants in CArdiovascular disease),10 conducted in 1994–1995. The study area was located in southern Germany and comprised the city of Augsburg and two surrounding counties. A sex–age stratified two-stage cluster sample was drawn from the population registers of the study area. The design of the MONICA survey has been described in detail elsewhere.7 In the 35–74 age group, a total of 5205 eligible persons were sampled from a study population of 286068. The subjects were invited to one of the 19 examination centres distributed over the whole study area. The response was 75.9% (n = 3950). Participants with self-reported myocardial infarction in the interview (n = 148) were excluded, leaving 3802 participants for the analysis presented here.

Unaffected siblings of myocardial infarction patients:

From October 1984 until July 1995, within the context of the WHO-MONICA Project, all cases of acute myocardial infarction occurring in the 25 to 74-year-old residents of the Augsburg area, were registered according to the MONICA protocol.11 From October 1996 until April 1997, the Augsburg Family Heart Study was conducted with the main objective to search genetic and environmental determinants of premature myocardial infarction. In October 1996, all living myocardial infarction patients registered between 1985 and 1994 and aged <60 years were contacted using a postal form. The myocardial infarction patients and their relatives were then invited and examined in the study centre. From the 874 eligible siblings (living and reached during the family study), 580 participated (participation rate 66.4%). Siblings aged <35 years (n = 13) or aged >74 years (n = 5) and with self-reported myocardial infarction in the interview (n = 38) were excluded from the study, leaving 524 unaffected siblings of myocardial infarction patients from 310 families. The German medical ethic committee approved the two studies and a consent form was signed by the participants.

Parameters

In both studies, the participants were interviewed and examined in an essentially identical manner. They underwent a standardised interview, three blood pressure measurements, weight and height were recorded, and a non-fasting blood sample was drawn (in sitting position in the MONICA study and in lying position in the Augsburg Family Heart Study). Serum levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, glucose, and HbA1c were measured. These analyses were performed in the laboratory of the central hospital of Augsburg. Quality control procedures were performed prior and during the data-gathering phase of the surveys.

Diabetes mellitus was defined as casual glucose concentration 11.1 mmol/l (casual venipuncture is defined as performed at any time of day without regard to the time since the last meal)12 or HbA1c >7%13 or current use of antidiabetic medication. Body weight and height were determined after removing shoes and heavy clothing. Body mass index was calculated as weight/height2 (kg/m2).

Level of education, cigarette smoking habits, alcohol consumption,14 sport and work activity were ascertained in the interview. The level of education was categorised in 10 years of education vs >10 years of education. Cigarette smoking was dichotomised as current regular smokers vs never, former or occasional (less than one cigarette/day) smokers. Alcohol consumption was treated as continuous parameter (g/day). An ‘active sportsman/woman’ was defined as a subject who participated in sports in summer and in winter. Also, sport activity had to be more than 1 hour per week in at least one season. An ‘active working man/woman’ was defined as a subject who had a heavy or moderate physical workload at the workplace or in the household.

Blood pressure was measured under highly standardised conditions to ensure internal and external comparability of the two studies. After at least 20 min at rest, SBP and DBP were measured on the right arm three times in a sitting position with the Hawksley random zero sphygmomanometer. All blood pressure values were based on the first and fifth phase of the Korotkoff sounds. SBP and DBP reported here are the average of the second and third measurements. Awareness was determined in both studies by the interview question: ‘Have you ever been told that your blood pressure was elevated or too high?’. Drug treatment was determined by recording all drugs taken over the preceding 7 days prior to the interview. In this study, participants who were unaware of their hypertension were not classified as users of antihypertensive medication. Antihypertensive medications were classified as ‘beta blockers’, ‘diuretics’, ‘ACE inhibitors’, ‘calcium channel blockers’, and ‘other antihypertensive drugs’. Using this classification, we studied whether the patient was treated with one, two, three or more classes of antihypertensive medication.

Hypertension was defined as a mean SBP 140 mm Hg and/or a mean DBP 90 mm Hg and/or use of an antihypertensive medication. According to the World Health Organization–International Society of Hypertension guidelines,9 grades of hypertension were classified: grade 1 or mild hypertension (SBP: 140 to 159 mm Hg, DBP: 90 to 99 mm Hg); grade 2 or moderate hypertension (SBP: 160 to 179 mm Hg, DBP: 100 to 109 mm Hg); grade 3 or severe hypertension (SBP 180 mm Hg, DBP 110 mm Hg). When a proband's SBP and DBP fell into different categories, the higher category was applied. Controlled hypertension was defined as a normal blood pressure level under antihypertensive medication. Pulse pressure was defined as the difference between the mean SBP and the mean DBP.

Statistical methods

Separate comparisons were carried out for men and women. Except for the use of antihypertensive medication, comparisons of the rates or means between the two groups were performed using the generalised estimating equation which permitted the different age structures of the two groups to be taken into account as well as the correlation among members of the same family. The use of antihypertensive medication was compared using logistic regression models because the number of members of the same family was too small in this subgroup. The statistical significance level was set at 0.05. Data were analysed using SAS 6.12 software, LOGISTIC and GENMOD procedures (SAS, Cary, NC, USA).

Results

Socio-demographic characteristics and coronary heart disease risk factors

The group of unaffected siblings consisted of 524 individuals: 46.2% were men and 53.8% were women. The reference group consisted of 3802 individuals: 48.8% were men and 51.2% were women. In both genders, the educational level was lower in the siblings group than in subjects from the reference group. The average ratios of total-cholesterol/HDL-cholesterol were not statistically different between the two male groups (borderline P-value). In women, the average ratio was lower in the sibling group than in subjects of the reference group. Due to the small number of patients under lipid-lowering medication in each group, the average ratio of total-cholesterol/HDL-cholesterol remained almost unchanged when users of lipid-lowering medication were excluded. Male siblings tended to be more often current regular cigarette smokers and drank less alcohol than the reference group. As for physical activity, male siblings had a lower sport activity than individuals from the reference group but a trend to a higher work activity was seen. In women, no statistical difference was demonstrated for smoking, alcohol consumption and physical activity. In both sexes, the prevalence of diabetes and average body mass index were not statistically different (Table 1).

Table 1 Comparison of the main coronary heart disease risk factors between unaffected siblings of myocardial infarction patients and the reference group

Blood pressure, prevalence of hypertension, pulse pressure

The mean value of DBP was higher in male siblings than in subjects of the reference group, whereas mean SBP was not statistically different between the two groups. In female siblings, mean SBP as well as mean DBP were higher than in the reference group (Table 2). The prevalence of hypertension was higher in siblings of myocardial infarction patients than in subjects of the reference group, with a clear statistical difference in women and with a borderline P-value in men. The comparison of the prevalence of the different grades of hypertension showed no statistical difference between male subjects of the two groups. Among women, the prevalence of mild and moderate hypertension was higher in siblings. The prevalence of controlled hypertension was higher in both gender but not statistically different between women of the two groups. Among men, the average pulse pressure was higher in the reference group than in the sibling group. Among women, no statistical difference was shown between the two groups.

Table 2 Comparison of prevalence of hypertension (defined as SBP 140 or DBP 90 or use of antihypertensive medication), blood pressure and pulse pressure means between unaffected siblings of myocardial infarction patients and the reference group

Table 3 shows the average pulse pressures by age group. Among men, the average pulse pressure tended to be higher in the reference group than in the sibling group with P-values under 0.05 in the age groups 35–44 and 65–74 years. Among women, no statistical difference was shown between the two groups in each age group.

Table 3 Comparison of pulse pressure means by age group between unaffected siblings of myocardial infarction patients and the reference group

Association between hypertension and sibling status (sibling vs reference group), adjusted for the main risk factors of hypertension

Among men, after adjusting for the main risk factors of hypertension (age, level of education, body mass index, alcohol intake, work and sport activity), the association between hypertension and sibling status was slightly stronger (OR = 1.39, P = 0.03) compared to the OR adjusted only for age (OR = 1.31, P = 0.06). Among women, adjustment for these risk factors did not substantially modify the OR (Table 4).

Table 4 Association between hypertension and sibling status (sibling vs reference group), adjusted for the main risk factors of hypertension.a Final models among men and women, using the generalised estimating equation

Awareness and treatment of hypertension

Male hypertensive siblings were more aware of their hypertension than male hypertensives of the reference group. Furthermore, male hypertensive siblings were treated more often for their hypertension than male hypertensives of the reference group. Conversely, among female hypertensives, neither the degree of awareness nor the degree of treatment were different between the two groups. In both genders, no significant difference in the degree of control was shown between hypertensive siblings and hypertensives of the reference group (Table 5).

Table 5 Comparison of treatment and awareness between hypertensive siblings of myocardial infarction patients and hypertensives of the reference group

ACE inhibitors were used more than twice as much in male siblings than in the reference group and tended to be used more often in female siblings than in the reference group but the difference was not statistically significant. Calcium channel blockers tended to be used more often in male hypertensives of the reference group. Diuretics were used less often in both male and female siblings (without statistical significance in men). In both genders, no significant difference in the degree of control was shown between antihypertensive medication users of the two groups. In male siblings, one class of hypertensives tended to be prescribed more often (without statistical significance). For the combination of medication, no differences were shown between the two female groups (Table 6).

Table 6 Comparison of the antihypertensive medication used in siblings of myocardial infarction patients and in the reference group

Discussion

The difference in the prevalence of hypertension between siblings of myocardial infarction patients and a reference group was previously demonstrated.15,16,17,18 However, the lack of comparability of the groups and of the study design resulted in a limitation of the analyses in most of these publications. One of the strengths of this present study was the comparability of the methods used to examine the two groups. Furthermore, the reference group was a population-based sample from the same study area from which the families were derived.

However, this study had also some limitations. Due to the selection bias inherent to our study design (ie, only living myocardial infarction patients and living siblings were reached) the levels of the main predictive factors of myocardial infarction mortality (hypertension, body mass index, ratio total-cholesterol/HDL-cholesterol) are probably underestimated in the sibling group: some of the subjects at high risk (ie, with a combination of hypertension and other cardiovascular risk factors) have probably died already. In men, this hypothesis could explain the low association between hypertension and sibling status which increased when adjusted for the other main risk factors of hypertension. Considering this selection bias, the comparison of the pulse pressure by age group can be interpreted as follows: patients with the highest pulse pressure values in siblings could not be included in the study, probably because of more premature deaths,19,20 leading to an inversion of the expected pulse pressures differences between the two groups in men and in the oldest age groups in women.

Another limitation is that multiple comparisons have been performed in this analysis (various risk factors and subgroups). The probability of a Type I error could be higher than 0.05 set as the threshold for statistical significance in this analysis. Consequently, the results must be carefully interpreted (particularly when the P-values are close to 0.05) and the significant differences need to be confirmed by further studies.

Concerning awareness and treatment of hypertension, the analysis showed that physicians detected hypertension more often in male siblings of myocardial infarction patients than in the reference group, which is encouraging from a public health point of view. However, this result is not transposable to women: among female hypertensives, there was no difference in the degree of awareness between the siblings and the reference group. The difference between men and women is probably due to the fact that women generally use health care more often than men. This increases the possibility for the physician to detect hypertension in women independently of their sibling status. Nevertheless, female siblings did not profit from this advantage; the degree of control in hypertensive siblings was as low in women as in men (under 13%) and at the same level as in the reference group. Furthermore, in both sexes, among antihypertensive medication users, the degree of control was as low in siblings as in the reference group (under 31.5%). These results show that siblings of myocardial infarction patients and/or treating physicians do not perceive the necessity to reinforce the prevention measures (particularly the control of hypertension) in families with heart disease. Similarly, US physicians do not appear to follow national recommendations for the screening of family members of patients with early cardiovascular disease.21,22

The use of antihypertensive medication was assigned only to the participants who where aware of their hypertension. This restriction was applied to avoid misclassification due to patients taking these medications for other cardiovascular conditions such as angina pectoris or congestive heart failure. The prevalence of antihypertensive medication users who are not aware of hypertension was very low in the two groups and in both sexes: 2.3% of the 1855 men of the reference group and 2.1% of the 242 male siblings were under antihypertensive medication but unaware of hypertension. Of the 1947 women of the reference group, 2.8% and of the 282 female siblings, 3.2% were under antihypertensive medication but unaware of hypertension. We re-examined the results given in Table 5 using the definition of antihypertensive medication use without the restriction on awareness. There were no substantial changes in the results.

ACE inhibitors were used more often in male and to a certain extent more often in female siblings than in the reference group. This more frequent prescription could be the consequence of other clinical conditions associated with hypertension which would indicate the use of ACE inhibitors9 like left ventricular hypertrophy or dysfunction or diabetic nephropathy. The difference in the study period between the reference group (1994/1995) and the Augsburg Family Heart Study (1996/1997) could also partly explain this result. We estimated the increase of the ACE inhibitor prescription, using a follow-up study of the last MONICA survey, conducted between 1997 and 1998. During the follow-up study, a postal self-administered questionnaire was sent to the same eligible sample. Of the 5137 contacted persons (aged 35–74 years), 2914 answered (participation rate: 56.7%). The use of ACE inhibitors among treated hypertensives increased between the surveys with an age-adjusted odds ratio of 1.52 (95% CI: 1.03–2.25) in men and with an age-adjusted odds ratio of 1.24 (95% CI: 0.84–1.82) in women.

In conclusion, this study confirms that the prevalence of hypertension is higher among siblings of myocardial infarction patients than in the general population for both sexes. Whereas the male hypertensive siblings of myocardial infarction patients were more treated than the general hypertensive population, no difference was found between the two female groups. In both sexes, the control of hypertension was as low in hypertensive siblings as in hypertensives drawn from the general population. From a public health perspective, efforts should still be undertaken to educate siblings of myocardial infarction patients to identify themselves as being at high risk. As suggested by Swanson et al,22 included in their hospital discharge plans, myocardial infarction patients could be given educational material on risk factors and how families are affected, inviting them to contact their siblings for screening. The World Health Organization–International Society of Hypertension guidelines, mentioned clearly family history of myocardial infarction as a risk factor which must be taken into account in the management strategy of hypertension.

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Acknowledgements

This study was supported by the Deutsche Forschungsgemeinschaft (DFG-FKZ:HO 1073/8-1) and the Bundesministerium für Bildung und Forschung (BMBF-FKZ: 01ER9502/0). We thank Anita Schuler and the KORA-team of the examination centre as well as the laboratory team of the central hospital for their technical support, Dr Margit Heier for the realisation of the medication database, Birgit Filipiak and Dr Annette Peters for their statistical support.

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Metzger, MH., Engel, S., Hengstenberg, C. et al. Do siblings of myocardial infarction patients have a specific management of hypertension?. J Hum Hypertens 16, 67–74 (2002). https://doi.org/10.1038/sj.jhh.1001296

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Keywords

  • family
  • myocardial infarction prevention and control
  • cardiovascular diseases epidemiology
  • antihypertensive agents therapeutic use

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