Summary
Background
Studies on the association between family history of cardiovascular disease and arterial stiffness are rare.
Aims
This study evaluated the possible relationship between family history of cardiovascular disease and arterial stiffness in the Japanese population, by measuring brachial-ankle pulse wave velocity (ba-PWV).
Methods
A total of 1004 eligible subjects (664 men and 340 women) aged 35–69 years, who were enrolled in the baseline survey of a cohort study in Tokushima Prefecture (Japan) and who underwent ba-PWV measurement, were analysed. Information about their lifestyle characteristics and first-degree family histories of ischaemic heart disease (i.e. myocardial infarction or angina pectoris), stroke or hypertension were obtained from a structural self-administered questionnaire.
Results
Subjects of both sexes with a family history of stroke showed significantly higher multivariable-adjusted means of ba-PWV than those without that trait ( P values were 0.001 in men and 0.002 in women), while those with a family history of ischaemic heart disease did not. Subjects of both sexes with a family history of hypertension showed significantly higher age-adjusted means of ba-PWV than those without that trait, although these differences disappeared after further adjusting for blood pressure or multivariable covariates. When family histories of these diseases were inserted simultaneously into the same model, these results did not alter substantially.
Conclusion
A family history of stroke might be associated with increased arterial stiffness, independent of other known atherosclerotic risk factors, including hypertensive elements, in both sexes in the Japanese population.
Résumé
Justification
Les études sur les associations entre les antécédents familiaux de maladie cardiovasculaire et la rigidité artérielle sont rares.
Objectifs
Cette étude a évalué la possible relation entre les antécédents familiaux de maladie cardiovasculaire et la rigidité artérielle au sein d’une population japonaise, en mesurant le paramètre vélocité de l’onde de pouls bras-cheville.
Méthode
Mille quatre sujets éligibles (664 hommes) âgés de 35 à 69 ans, ont été inclus au sein de cette cohorte de la préfecture de Tokushima au Japon et ont bénéficié d’une mesure de la vélocité de l’onde de pouls bras-cheville, paramètre qui a été analysé. L’information concernant les caractéristiques de base, le mode de vie, les antécédents familiaux de maladie coronaire de 1 er degré (infarctus du myocarde ou angine de poitrine), d’infarctus cérébral et d’hypertension artérielle ont été obtenus à partir d’un questionnaire structuré renseigné par les patients.
Résultats
Les sujets des deux sexes ayant un antécédent familial d’infarctus cérébral avaient des moyennes de vélocité de l’onde de pouls bras-cheville dans les deux sexes significativement plus élevées ( p = 0,001 chez l’homme et p = 0,002 chez la femme), comparativement aux sujets n’ayant pas de tels antécédents, tandis que les patients ayant un antécédent familial de cardiopathie ischémique n’avaient pas de différence significative concernant ce paramètre. Les sujets des deux sexes ayant un antécédent familial d’hypertension artérielle avaient également des valeurs moyennes de cet indice plus élevées, comparativement aux sujets n’ayant pas ce trait, mais ces différences n’étaient plus significatives après ajustement sur la pression artérielle ou sur les co-variables en analyse multivariée. Lorsque les antécédents familiaux de ces affections cérébro-vasculaires et ischémiques étaient inclus dans le même modèle, ces résultats n’étaient pas modifiés de façon significative.
Conclusion
Un antécédent familial d’infarctus cérébral pourrait être potentiellement associé avec une augmentation de la rigidité artérielle, indépendamment des autres facteurs de risque d’athérosclérose connus, hypertension artérielle en particulier, et ce dans les deux sexes, dans une population japonaise.
Background
Cardiovascular events are major causes of death worldwide. Atherosclerosis is the main factor leading to cardiovascular events. Arterial stiffness is an indicator of atherosclerotic vascular change and can be assessed by measuring pulse wave velocity (PWV) . Many epidemiological studies have reported positive associations between PWV and the development of atherosclerotic disease . PWV is recognized as a marker of the severity of vascular damage ; moreover, it is a predictor of cardiovascular events and mortality . Brachial-ankle PWV (ba-PWV) can be measured conveniently and non-invasively, and is useful for evaluating the early stages of atherosclerosis .
Mortality due to ischaemic heart disease is less frequent in Japan than in Western countries . However, mortality and morbidity due to stroke are more frequent in Japan, especially in men . Recent studies have revealed that increased PWV is associated with coronary and cerebral atherosclerosis . Family history is a risk factor for many chronic diseases, including hypertension, ischaemic heart disease and stroke . However, little is known about the influence of family history of cardiovascular disease on arterial stiffness. Therefore, this study evaluated the possible relationship between a family history of ischaemic heart disease, stroke or hypertension and arterial stiffness in the Japanese population.
Methods
Study subjects
A total of 1065 participants aged 35–69 years, who were enrolled in the baseline survey of a prospective cohort study in Tokushima Prefecture (Japan), and who underwent measurement of ba-PWV and serum lipid concentration at the baseline survey from November 2009 to June 2012 were included in this cross-sectional study. This cohort study was performed as part of the prospective cohort study (the Japan Multi-Institutional Collaborative Cohort [J-MICC] Study), as described previously . Briefly, the aim of the J-MICC Study is to examine the associations of lifestyle and genetic factors and their interactions with lifestyle-related diseases. All participants in the J-MICC Study provided written informed consent. The ethics committees of the Nagoya university school of medicine (the affiliation of the former principal investigator [Nobuyuki Hamajima]), the Aichi cancer centre (the affiliation of the current principal investigator [Hideo Tanaka]) and the university of Tokushima graduate school approved the protocol of this study.
Questionnaire
We obtained information on individual lifestyle characteristics for the past year through a structural self-administered questionnaire; all the responses were reviewed by trained staff at the time of the survey. Leisure-time exercise was estimated based on the International Physical Activity Questionnaire . Exercise was divided into three levels: light exercise, such as walking or hiking; moderate exercise, such as light jogging or swimming; and vigorous exercise, such as marathon running or competitive sports. Degrees of leisure-time exercise for the three levels were expressed as metabolic equivalent of task (MET)-hours/week (MET level × hours of activity × events per week) and summed . In this estimation, 3.4 METs were assigned for light exercise, 7.0 METs for moderate exercise and 10.0 METs for vigorous exercise. Body height was obtained from the questionnaire; body weight was measured to the nearest 0.1 kg at the survey. Body mass index was calculated as weight (in kilograms) divided by height (in meters) squared. Additionally, we obtained information regarding first-degree family histories of ischaemic heart disease, including myocardial infarction or angina pectoris, stroke and hypertension (i.e. positive, negative or unknown). When analysed, a response of ‘positive’ was regarded as having a family history of the disease, whereas ‘negative’ and ‘unknown’ were regarded as not having a family history of the disease.
Pulse wave velocity and biochemical measurements
ba-PWV was measured using a waveform analyser (model BP-203RPE III; Colin, Co. Ltd., Komaki, Japan), as described previously . Briefly, the subjects were examined while resting in the supine position in an air-conditioned room. Extremity blood pressure was measured using an oscillometric method and the ankle-brachial pressure index (ABI) was automatically calculated. Heart rate was recorded simultaneously. ba-PWV was calculated using time-phase analysis between the right brachial artery pressure and volume waveforms at both ankles. To reduce interobserver variation, all ba-PWV measurements were performed by one researcher throughout the study. Individual ba-PWV and ABI data are expressed as the mean of the bilateral ba-PWV and ABI, respectively. Venous blood was aspirated from each participant and serum was separated within 3 hours. Serum lipid concentrations were measured at an external laboratory (BML Inc., Tokyo, Japan).
Statistical analyses
Among the 1065 participants (710 men and 355 women) initially included in this cross-sectional study, we excluded 34 with a history of ischaemic heart disease ( n = 21) and stroke ( n = 16). We excluded another five subjects who had a low right or left ABI (ABI ≤ 0.9), which suggested that they might have had peripheral arterial occlusive disease. There were no subjects who self-reported a history of cirrhosis or hepatic cancer. We further excluded subjects with missing data on family history of cardiovascular diseases ( n = 10). After excluding an additional 12 subjects for whom serum lipid concentration data were missing, 1004 subjects (664 men and 340 women) were finally included in the analyses.
Continuous variables are expressed as mean ± standard deviation or median (25 percentile, 75 percentile). Categorical variables are expressed as proportion (%). Student’s t test, Wilcoxon rank-sum test and Fisher’s exact test were used to compare baseline characteristics between subjects with and without a family history of diseases.
Prevalent hypertension was defined as systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg or receiving antihypertensive treatment. Hypercholesterolaemia was defined as serum total cholesterol ≥ 220 mg/dL or receiving treatment for hypercholesterolaemia, and low high-density lipoprotein (HDL) cholesterol was defined as serum HDL cholesterol < 40 mg/dL. Elevated triglycerides were defined as serum triglycerides ≥ 150 mg/dL. Prevalent diabetes was defined as having a history of diabetes. We used general linear models to evaluate the associations of family histories of ischaemic heart disease, stroke or hypertension with ba-PWV values in men and women separately, after adjusting for the probable covariates. Adjusted covariates were as follows: age (continuous) (model 1); age and systolic blood pressure (< 120, 120 to < 140, 140 to < 160, ≥ 160 mmHg without treatment and receiving antihypertensive treatment) (model 2); age, systolic blood pressure, body mass index (kg/m 2 ) (sex-specific quartiles), smoking status (current, past and never), alcohol drinking (current, past and never), leisure-time exercise (MET hours/week) (sex-specific quartiles), hypercholesterolaemia (no/yes), low HDL cholesterol (no/yes), elevated triglycerides (no/yes), diabetes (no/yes) and heart rate (continuous), with experienced menopause (no/yes) included for women (model 3). We further evaluated the associations of family histories of ischaemic heart disease, stroke or hypertension with ba-PWV values in additional models; family histories of these diseases were inserted simultaneously into the models, to avoid their overlapping influences, adjusting for age (model 4), age and systolic blood pressure (model 5) and the same covariates as in model 3 (model 6).
All statistical tests were based on two-sided probabilities performed using SAS version 8.2 (SAS Institute Inc., Cary, NC, USA). The level of statistical significant was set at P < 0.05.
Results
Baseline characteristics
Age was significantly correlated with ba-PWV in both sexes ( r = 0.492, P < 0.001 in men and r = 0.534, P < 0.001 in women). Systolic blood pressure was also strongly correlated with ba-PWV in both sexes ( r = 0.646, P < 0.001 in men and r = 0.770, P < 0.001 in women). There were no significant differences between sexes in the proportions with family histories of ischaemic heart disease, stroke or hypertension (data not shown).
Tables 1 and 2 show the characteristics of the subjects with and without family histories of ischaemic heart disease, stroke or hypertension in men and women, respectively. Men had considerably higher ba-PWV values than women. Subjects of both sexes with a family history of ischaemic heart disease or stroke were older than those without such a family history. Subjects of both sexes with a family history of stroke or hypertension had significantly higher systolic blood pressure and higher prevalence of hypertension than those without such a family history, while those with a family history of ischaemic heart disease did not. Subjects of both sexes with a family history of stroke or hypertension showed significantly higher ba-PWV values than those without such a family history. Women with a family history of ischaemic heart disease had significantly higher ba-PWV values than those without that trait, while men with a family history of ischaemic heart disease did not.
| Family history | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Ischaemic heart disease | Stroke | Hypertension | |||||||
| No ( n = 541; 81.5%) | Yes ( n = 123; 18.5%) | P | No ( n = 558; 84.0%) | Yes ( n = 106; 16.0%) | P | No ( n = 343; 51.7%) | Yes ( n = 321; 48.3%) | P | |
| Age (years) | 48.5 ± 8.6 | 50.6 ± 8.3 | 0.013 | 48.4 ± 8.5 | 51.8 ± 8.4 | < 0.001 | 48.3 ± 8.6 | 49.5 ± 8.6 | 0.070 |
| Body mass index (kg/m 2 ) | 24.5 ± 3.4 | 24.5 ± 3.2 | 0.920 | 24.6 ± 3.5 | 24.0 ± 2.7 | 0.081 | 24.4 ± 3.5 | 24.6 ± 3.2 | 0.553 |
| Smoking status | |||||||||
| Never | 30.3 | 27.6 | 30.1 | 28.3 | 28.9 | 30.8 | |||
| Past | 34.9 | 41.5 | 0.413 | 34.2 | 46.2 | 0.044 | 36.2 | 36.1 | 0.827 |
| Current | 34.8 | 30.9 | 35.7 | 25.5 | 35 | 33 | |||
| Alcohol drinking | |||||||||
| Never | 26.1 | 17.9 | 24.7 | 23.6 | 26.5 | 22.4 | |||
| Past | 1.8 | 0.8 | 0.111 | 1.6 | 1.9 | 0.882 | 1.2 | 2.2 | 0.308 |
| Current | 72.1 | 81.3 | 73.7 | 74.5 | 72.3 | 75.4 | |||
| Exercise (MET-hours/week) | 3.9 (0.4, 14.0) | 5.6 (1.3, 15.3) | 0.156 | 3.9 (0.4, 14.0) | 7.7 (2.6, 17.9) | 0.002 | 4.3 (0.4, 15.3) | 5.1 (1.3, 15.3) | 0.316 |
| Systolic BP (mmHg) | 134.1 ± 16.2 | 137.1 ± 17.7 | 0.069 | 134.1 ± 16.3 | 137.8 ± 17.6 | 0.036 | 132.4 ± 15.2 | 137.1 ± 17.6 | < 0.001 |
| Diastolic BP (mmHg) | 84.0 ± 11.3 | 85.5 ± 11.3 | 0.183 | 84.0 ± 11.2 | 85.8 ± 11.6 | 0.137 | 82.7 ± 10.8 | 86.0 ± 11.6 | < 0.001 |
| Heart rate (beats/min) | 66.8 ± 10.1 | 68.5 ± 12.2 | 0.152 | 67.3 ± 10.6 | 66.2 ± 10.2 | 0.327 | 66.5 ± 10.2 | 67.8 ± 10.9 | 0.108 |
| Total cholesterol (mg/dL) | 211.8 ± 35.0 | 212.5 ± 31.1 | 0.839 | 212.3 ± 34.5 | 210.4 ± 33.2 | 0.598 | 210.3 ± 34.8 | 213.7 ± 33.7 | 0.198 |
| HDL cholesterol (mg/dL) | 56.2 ± 11.9 | 56.8 ± 11.9 | 0.572 | 56.3 ± 11.9 | 56.4 ± 12.0 | 0.934 | 55.8 ± 12.3 | 56.8 ± 11.4 | 0.305 |
| Triglycerides (mg/dL) | 111 (75, 164) | 106 (77, 148) | 0.575 | 107 (75, 155) | 117.5 (84, 172) | 0.029 | 111 (74, 165) | 107 (79, 155) | 0.923 |
| Prevalence | |||||||||
| Hypertension | 44.2 | 53.7 | 0.071 | 43.9 | 56.6 | 0.019 | 38.8 | 53.6 | < 0.001 |
| Hypercholesterolaemia | 40.3 | 43.9 | 0.478 | 41.4 | 38.7 | 0.667 | 39.7 | 42.4 | 0.479 |
| Low HDL cholesterol | 4.8 | 4.9 | 1.000 | 4.3 | 7.6 | 0.211 | 6.7 | 2.8 | 0.028 |
| Elevated triglycerides | 29.9 | 23.6 | 0.186 | 27.4 | 35.9 | 0.081 | 30.6 | 26.8 | 0.304 |
| Diabetes | 3.9 | 7.3 | 0.144 | 4.7 | 3.8 | 1.000 | 4.4 | 4.7 | 0.854 |
| ABI | 1.12 ± 0.06 | 1.13 ± 0.06 | 0.138 | 1.12 ± 0.07 | 1.14 ± 0.06 | < 0.001 | 1.12 ± 0.07 | 1.13 ± 0.06 | 0.045 |
| ba-PWV (cm/s) | 1432 ± 229 | 1466 ± 268 | 0.193 | 1419 ± 220 | 1537 ± 293 | < 0.001 | 1409 ± 217 | 1468 ± 253 | 0.001 |
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