Household cardiovascular screening of high-risk families: a school-based study.

Abstract

A parental history of cardiovascular disease has a strong relationship with risk factor clusters in the offspring. This study was performed to identify major cardiovascular risk factors in middle school-aged children and their parents in both high and low-risk families.
A school-based, cross-sectional study.
The middle schools of the 6th district of Tehran were divided randomly into two groups. A total of 169 high-risk children with their families were recruited from the first group and 105 low-risk children with their families were recruited from the second group of schools. Anthropometric and metabolic measurements were performed.
The means of the waist circumference and waist-to-hip ratio were significantly higher in high-risk fathers. The means of total and low-density lipoprotein (LDL) cholesterol were significantly higher in both parents and children of the high-risk group. The means of the fasting plasma glucose were significantly higher in fathers and offspring of high-risk families. More fathers in high-risk families were smokers. The prevalence of increased total cholesterol, LDL-cholesterol and hyperglycemia (> or = 100 mg/dl) were higher in high-risk parents and children. The prevalence of increased body mass index (> or = 25 kg/m for parents and 85th percentile for children) was higher in fathers and children of high-risk families.
Cardiovascular risk factors are more prevalent and clustered in high-risk families. The screening of high-risk families is essential to prevent the progression of atherosclerosis from childhood and reduce the burden of cardiovascular disease in adulthood.

Full text

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Original Scientific Paper
Household cardiovascular screening of high-risk families:
a school-based study
Rasoul Pourebrahim, Hossein Fakhrzadeh, Fatemeh Bandarian,
Ozra Tabatabaie, Masoomeh Noori, Forouzan Djalilpour, Farzaneh Zahedi,
Iman Rahimi, Ramin Heshmat, Ebrahim Djavadi, Sara Ghotbi and Bagher Larijani
Endocrinology and Metabolism Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Received 1 December 2004 Accepted 20 January 2006
Background A parental history of cardiovascular disease has a strong relationship with risk factor clusters in the offspring.
This study was performed to identify major cardiovascular risk factors in middle school-aged children and their parents in
both high and low-risk families.
Design A school-based, cross-sectional study.
Methods The middle schools of the 6th district of Tehran were divided randomly into two groups. A total of 169 high-risk
children with their families were recruited from the first group and 105 low-risk children with their families were recruited
from the second group of schools. Anthropometric and metabolic measurements were performed.
Results The means of the waist circumference and waist-to-hip ratio were significantly higher in high-risk fathers. The
means of total and low-density lipoprotein (LDL) cholesterol were significantly higher in both parents and children of the
high-risk group. The means of the fasting plasma glucose were significantly higher in fathers and offspring of high-risk
families. More fathers in high-risk families were smokers. The prevalence of increased total cholesterol, LDL-cholesterol
and hyperglycemia (ZZ100mg/dl) were higher in high-risk parents and children. The prevalence of increased body mass
index (ZZ25kg/m2for parents and 85th percentile for children) was higher in fathers and children of high-risk families.
Conclusions Cardiovascular risk factors are more prevalent and clustered in high-risk families. The screening of high-risk
families is essential to prevent the progression of atherosclerosis from childhood and reduce the burden of cardiovascular
disease in adulthood. Eur J Cardiovasc Prev Rehabil 13:229–235? c 2006 The European Society of Cardiology
European Journal of Cardiovascular Prevention and Rehabilitation 2006, 13:229–235
Keywords: cardiovascular disease, cholesterol, obesity, screening, risk factors
Sponsorship: This study was supported by Endocrinology and Metabolism Research Center grant LD1006, 2003.
Introduction
There has been an alarming increase in the incidence of
coronary heart disease (CHD) in Asian countries and the
Middle East crescent during the past few decades [1,2].
This is attributed to urbanization, worldwide technologi-
cal changes, economic growth and its effects on the
lifestyle of people in this region. Currently, cardiovascular
disorders are the leading cause of death in Iran,
accounting for nearly 46% of total deaths [3]. CHD is
the predominant form, with approximately 2.5 deaths for
every stroke death [3]. Atherosclerosis begins early in life,
and children exhibit cardiovascular risk factors at similar
frequencies to adults [4,5]. Clusters of multiple risk
factors often track into adulthood and are predictive of
future cardiovascular risk [6–9].
Lifestyle and health-related behaviours gradually take
form from childhood, consolidate before the age of 10
years, and the attitudes of adults in the families play the
key role in the development of behavioural risk factors
in their offspring [10,11]. On the other hand, there is
Correspondence and requests for reprints to Hossein Fakhrzadeh, Endocrinology
and Metabolism Research Center, Dr Shariati University Hospital, North Kargar
Avenue, Tehran 14114, Iran.
Tel: +9821 88026902 3; fax: +9821 88029399;
e-mail: emrc@sina.tums.ac.ir
1741-8267 ? c 2006 The European Society of Cardiology
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compelling evidence for familial aggregation of CHD
favoured by genetic and environmental factors [12,13].
The available data suggest that there are certain at-risk
families that are responsible for much of the CHD
burden in different communities [14]. A positive family
history of CHD is generally associated with a 1.5 to
twofold increase in the risk of CHD among first-degree
relatives [15]. A parental history of cardiovascular disease
(CVD) at less than 65 years of age has a strong
relationship with the risk factor clusters in the offspring
[16].
The detection and treatment of CHD risk factors from
early childhood is essential to reduce the prevalence of
disease in adulthood. In recent years, a number of studies
have shown an increasing trend in CHD risk factors
among Iranian children [17]; however, screening for risk
factors is generally not performed in this country, even in
families with a high prevalence of CHD. In this study we
aimed to identify and evaluate major cardiovascular risk
factors among middle school-aged children and their
parents. We also evaluated whether the involvement of
the children can be an effective means to increase
participation of the families in the screening programme.
Methods
This study was conducted with middle school-aged
children, that is, sixth to eighth graders, and their parents
in the sixth district of Tehran. The schools were randomly
divided into two groups A and B to recruit high and low-
risk families, respectively. In this way we tried to reduce
the effect of the interaction between high and low-risk
families, because it was our hypothesis that high-risk
families would probably take part in the study more than
low-risk families. In each household the offspring and
his/her parents with other siblings were investigated
for cardiovascular risk factors. High-risk families were
defined as those with a positive history of major
cardiovascular endpoints that had occurred before 65
years of age for women or before 55 years of age for men
in the household, or the presence of at least two classic
CVD risk factors, namely dyslipidemia, hypertension,
diabetes and smoking in at least one of the parents or
grandparents of the children. The presence of CVD or its
risk factors was detected through a self-administered
questionnaire that was completed by the parents in the
home.
The research team attended the schools to invite families
of children to take part in the study. A detailed verbal
explanation about the growing CVD burden in the
country, its risk factors, and the necessity of implement-
ing preventative measures from early childhood was given
to the pupils in the morning ceremony at the schools.
A brochure was then distributed to pupils that included a
brief description of the above items in common language
and the concept of being at high risk. Each pupil was
requested to deliver this brochure to his/her parents and
to explain its contents to them. In group A schools,
families were invited to attend a school-based clinic if
they were high risk. In group B schools, the households
that were free of a history of cardiovascular endpoints or
CVD risk factors were invited to the clinic. Written
informed consent was obtained from each of the house-
holds signed by the father of the family.
In the clinic, a structured questionnaire was filled in by
the parents that included enquiries about socio-economic
status, educational level, the frequency, quality and level
of physical activities, nutrition (i.e. the intake of
saturated fatty acid, fibre and salt) and smoking. A
general physical examination was also performed for both
parents and children. Standing height was measured to
the nearest 0.5cm (Seca Stadiometer) and weight was
measured to the nearest 0.5kg (Seca Beam Balance),
wearing minimum indoor clothing and barefoot, and the
body mass index (BMI) was calculated. Waist and hip
circumferences were measured and the waist-to-hip ratio
(WHR) was estimated. The blood pressure was measured
twice on the right arm using an appropriate cuff-sized
mercury sphygmomanometer with the subject sitting
quietly for at least 5min. The mean of two measurements
of Korotkoff’s phase I and the mean of two values of
phase IV were recorded as systolic and diastolic blood
pressure, respectively. Venous blood was collected with
minimum stasis to determine the metabolic parameters.
Subjects had been fasting for 12h and had rested for
15min before the venipuncture. Serum total cholesterol,
triglyceride, low-density lipoprotein (LDL) cholesterol,
high-density lipoprotein (HDL) cholesterol and glucose
concentrations were analysed using an auto analyser (BM
Hitachi-747; Boehringer Mannheim GmbH, Mannheim,
Germany) employing the original kits for enzymatic-
colorimetric methods (Boehringer Mannheim).
Definitions
Parents
Cutoff points for lipid parameters were determined
according to the National Cholesterol Education Program;
Adult Treatment Panel III guidelines [18]. Total
cholesterol200mg/dl or
160mg/dl or greater, HDL-cholesterol less than 40mg/
dl and triglycerides 200mg/dl or greater were considered
as dyslipidemia. Hypertension was defined as systolic
blood pressure of 140mmHg or higher or diastolic blood
pressure of 90mmHg or higher or the use of antihyper-
tensive drugs [19]. Regular smokers were those who
smoked at least one cigarette per day. Diabetes was
defined as fasting plasma glucose (FPG) values of
126mg/dl or greater or the use of glucose-lowering drugs
or insulin. For those not taking glucose-lowering drugs or
insulin, FPG between 100 and 125mg/dl was considered
as impaired fasting glucose (IFG) [20]. Overweight,
greater, LDL-cholesterol
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obesity and extreme obesity were defined as a BMI of
25.0–29.9, 30.0 or more, and 40.0kg/m2
respectively [21]. Visceral obesity assessed by WHR was
defined as over 0.95 for men and over 0.85 for women,
respectively; or else a waist circumference of 102cm or
more for men and 88cm or more for women were the cut-
off points for visceral obesity. Regular physical activity
was defined as moderate aerobic exercise performed
5 days a week with a duration of at least 20min per day
according to self-report.
or more,
Children
Reference values for dyslipidemia were taken from the
National CholesterolEducation
[22,23]. Hypertension was defined as average systolic or
diastolic blood pressure greater than or equal to the 95th
percentile of age, sex and height on at least three separate
occasions [24]. Obesity was regarded as a BMI of the 95th
or greater age and sex-specific percentile, whereas over-
weight was considered as a BMI between the 85th and
94.9th age and sex-specific percentile [25]. Physical activity
in children was defined as in their parents (see above).
Programguidelines
Statistical analysis
Statistical analysis was performed using SPSS software,
version 12 (SPSS Inc., Chicago, Illinois, USA). Measure-
ments of continuous variables were expressed as means
and standard deviations (SD). Significance of differences
was tested using Student’s t-test if the variable was
continuous; and in the case of nominal variables by the
chi-squared test and expressed as P values. Binomial
logistic regression analysis was used to determine the
relationship between independent parental factors and
being a high-risk child.
Results
As a whole, 169 (84%) high and 105 (71%) low-risk
families participated in the survey (P<0.03). There was
no statistically significant difference between the high
and low-risk families with relation to socio-economic
status. The means of age, anthropometric and blood
pressure values of both groups are presented in Table 1.
There were no statistically significant differences in the
means of age, BMI and blood pressure of the parents and
children between the two groups. The means of waist
circumference and WHR were significantly higher in the
fathers of high than those of low-risk families (P=0.003
and P<0.05, respectively). The means of metabolic
values between the groups are presented in Table 2. Total
cholesterol and LDL-cholesterol were much higher in the
parents and children of the high-risk group (P<0.001 for
all). FPG levels were higher in the fathers and children of
high than low-risk families (P<0.001 for all).
The prevalence of CHD risk factors in the parents and
children of the two groups are represented in Tables 3
and 4. More fathers in the high-risk families were active
smokers. In fathers of the high-risk group 108 (63.9%)
were overweight, 18 (10.6%) were obese and four (2.3%)
were morbidly obese, whereas in the low-risk group 53
(50.4%) were overweight, eight (7.6%) were obese and
one (0.9%) had morbid obesity (P<0.01). In mothers of
the high-risk group 70 (41.1%) were overweight, 46
(27.5%) were obese and three (1.8%) were morbidly
obese, whereas in the low-risk group 48 (54.3%) were
overweight and 13 (15.2% ) were obese (P<0.05). In
children of the high-risk group 34 (20.1%) were over-
weight and six (1.5%) were obese, whereas in children of
the low-risk group 10 (9.5%) were overweight and three
(2.8%) were obese (P<0.001).
Of the fathers in the high-risk group 25 (14%) had
diabetes and 76 (45%) had IFG, whereas in the low-risk
group three (2.9%) fathers had diabetes and 18 (17%) had
IFG (P<0.0001). Of the high-risk mothers, nine (5.3%)
had diabetes and 55 (32.5%) had IFG, whereas in the low-
risk mothers, nine (8.6%) had diabetes and 16 (15.1%)
had IFG (P<0.04). None of the children were found to
have diabetes; however, 58 of the high-risk versus 13 of
the low-risk children had IFG (P<0.001).
Thirty-four per cent of overweight/obese children in the
high-risk and 12% of the overweight/obese offspring in
the low-risk group had IFG (P<0.001).
Table 1
Means of anthropometric and blood pressure values of children and parents in high and low coronary heart disease risk families
FathersMothersChildren
High risk
n=169a
Low risk
n=105a
P valueHigh risk
n=169a
Low risk
n=105a
P valueHigh risk
n=169a
Low risk
n=105a
P value
Age (years)
Height (cm)
Weight (kg)
BMI (kg/m2)
WC (cm)
HC (cm)
WHR
SBP (mmHg)
DBP (mmHg)
43.9±3.9
173.3±7.0
82.1±11.5
28.8±19.9
98.5±8.6
104.3±5.9
0.94±0.10
107.7±13.3
70.2±9.2
43.2±2.1
167.6±20.9
76.3±15.1
27.4±3.6
93.2±9.3
103.4±9.4
0.89±0.09
112.3±16.8
69.3±8.1
NS
NS
0.04
NS
0.003
NS
0.05
NS
NS
40.9±5.2
158.3±5.2
69.7±12.7
27.8±4.8
90.8±15.9
106.4±9.1
0.85±0.08
113.1±14.0
76.1±9.6
41.6±6.0
157.4±10.5
69.3±11.2
28.4±7.6
87.1±10.9
104.3±9.9
0.83±0.09
115.2±12.1
75.4±10.4
NS
NS
NS
NS
NS
NS
NS
NS
NS
12.1±0.4
156.6±7.0
53.6±12.9
21.7±4.5
75.6±10.5
91.1±9.2
0.83±0.11
97.5±19.7
63.3±6.9
12.3±0.2
156.0±14.7
48.4±11.5
21.4±16.9
75.7±10.8
92.2±10.3
0.82±0.10
102.2±12.2
62.8±7.1
NS
NS
0.002
NS
NS
0.01
NS
NS
NS
BMI, Body mass index; DBP, diastolic blood pressure; HC, hip circumference; SBP, systolic blood pressure; WC, waist circumference; WHR, waist-to-hip ratio.aValues
are written as mean±SD.
Household cardiovascular screening Pourebrahim et al.
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Less than 30% of parents and offspring in both the high
and low-risk families were doing regular exercise.
We calculated the risk score of the children by assigning a
unit number to each of the classic risk factors, namely a
positive family history of premature CVD, hypertension,
hyper-LDL, hypertriglyceridemia, hypo-HDL, glucose
intolerance and overweight/obesity in the offspring and
adding the number of risk factors they had. High-risk
children were those who had at least two of these risk
factors.
Binomial logistic regression analysis revealed that only
age-adjusted maternal obesity, diabetes mellitus, hyper-
tension and dyslipidemia had a significant relationship
with being a high-risk child [odds ratio 4.17, 95%
confidence interval (CI) 1.92–9.06]. No correlation was
found between paternal factors such as obesity, hyperten-
sion, diabetes and dyslipidemia, and being high risk in
children. The adjusted odds ratio for obesity of fathers
and high-risk children was 0.77 (95% CI 0.27–2.21). No
obvious relationship was detected between being a
high-risk child with the presence of premature death
caused by CVD in the grandparents.
Discussion
The results of this study suggest that it is essential to
screen for cardiovascular risk factors from childhood in
high-risk families, because childhood and adolescence are
crucial periods for the development of risk-related
behaviours. On the other hand, young unaffected
members of high-risk families have a greatly increased
risk of early-onset CHD. We found that many of the
traditional CHD risk factors were more prevalent in
parents and children of the high-risk families compared
with those from low-risk families.
The most consistent findings in our study were the
higher total cholesterol and LDL-cholesterol levels in
high-risk parents and children compared with the low-risk
families, which are similar to the findings of Barth et al.
[26] that showed significantly higher total cholesterol and
LDL-cholesterol values in children with a positive family
history of premature CHD. In addition, this difference in
total cholesterol and LDL-cholesterol levels was also
present between the parents of the high and low-risk
groups in our study. However, we found no significant
difference in HDL-cholesterol and triglyceride levels
between the high and low-risk groups. In a recent study
of atherosclerosis risk factors in Iranian children [27],
Table 2
Means of metabolic parameters of parents and children in high and low coronary heart disease risk families
FathersMothers Children
High risk
n=169a
Low risk
n=105a
P valueHigh risk
n=169a
Low risk
n=105a
P value High risk
n=169a
Low risk
n=105a
P value
Total cholesterol (mg/dl)
LDL-cholesterol (mg/dl)
HDL-cholesterol (mg/dl)
FBG (mg/dl)
Uric acid (mg/dl)
Triglycerides (mg/dl)
217.8±40.6
140.0±30.3
61.9±17.5
110.2±28.1
5.1±1.2
198.4±42.1
173.9±32.9
103.4±25.3
58.6±13.9
93.8±10.6
5.6±1.7
202.0±38.4
0.0001
0.0001
NS
0.0001
NS
NS
201.9±37.9
123.1±29.1
64.9±19.9
101.7±35.5
3.7±0.9
140.0±48.1
176.7±39.7
103.7±28.9
60.9±18.7
98.2±28.1
3.5±1.1
146.2±43.2
0.0001
0.0001
NS
NS
NS
NS
163.4±36.7
98.1±25.4
50.7±14.8
89.7±15.3
3.8±1.0
126.9±39.2
142.0±29.0
77.7±21.6
49.7±16.8
67.2±6.8
4.0±0.8
121.7±34.8
0.0001
0.0001
NS
FBG, Fasting blood glucose; HDL, high-density lipoprotein; LDL, low-density lipoprotein.aValues are written as mean±SD.
Table 3
Coronary heart disease risk factors of parents in high and low coronary heart disease risk families
Fathers Mothers
High risk n (%)Low risk n (%)
P valueHigh risk n (%)Low risk n (%)
P value
Current smoker
BMI Z25kg/m2
Hypertension
Total cholesterol Z200mg/dl
LDL-cholesterol Z130mg/dl
HDL-cholesterol <40mg/dl
Triglycerides Z200mg/dl
Regular exercise
FBG Z100
69 (41%)
130 (76%)
30 (18%)
109 (64%)
44 (26%)
15 (9%)
98 (58%)
38 (22.4%)
104 (66%)
21 (20%)
62 (58%)
18 (17%)
34 (32%)
1 (1%)
11 (10%)
59 (56%)
23 (21.9%)
21 (20%)
<0.01
<0.01
NS
<0.0001
<0.0001
NS
NS
NS
<0.0001
14 (8%)
119 (70%)
13 (8%)
89 (53%)
21 (12%)
18 (11%)
64 (38%)
29 (17.1%)
64 (56%)
10 (9%)
73 (69%)
10 (9%)
19 (18%)
5 (4%)
15 (14%)
39 (37%)
19 (18.1%)
26 (25%)
NS
NS
NS
<0.0001
<0.003
NS
NS
NS
<0.04
BMI, Body mass index; FBG, fasting blood glucose; HDL, high-density lipoprotein; LDL, low-density lipoprotein.
Table 4
low coronary heart disease risk families.
Coronary heart disease risk factors of children in high and
Children
High risk n (%) Low risk n (%)
P value
Hypertension
High total cholesterol (>95th)
High LDL-cholesterol (>95th)
Low HDL-cholesterol (<5th)
High triglycerides (>95th)
Regular exercise
FBG Z100
Overweight/obese
13 (8%)
22 (10%)
15 (9%)
20 (12%)
38 (22%)
46 (27%)
58 (34%)
40 (22%)
12 (10%)
4 (4%)
3 (3%)
16 (15%)
24 (23%)
31 (29.5%)
13 (12%)
13 (12%)
NS
<0.0001
<0.0001
NS
NS
NS
<0.001
<0.001
FBG, Fasting blood glucose; HDL, high-density lipoprotein; LDL, low-density
lipoprotein.
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it was found that total cholesterol, LDL-cholesterol,
triglycerides and apolipoprotein B100 were significantly
higher, whereas apolipoprotein A1 and HDL-cholesterol
were significantly lower in the offspring of families with a
history of premature CHD. In contrast to these findings,
no significant differences were found in the concentra-
tions of lipids and lipoproteins between the offspring of
the high and low-risk families by other investigators [28].
The strong correlation between the lipid levels of the
parents and their offspring in this study is similar to the
findings from previous studies [29,30].
It is necessary to lower the average blood cholesterol level
in all of the parents and offspring with hypercholester-
olemia, as children and adolescents with high cholesterol
levels are more prone to have high plasma cholesterol
levels when they are adults [31–33].
Our finding of an increased prevalence of overweight/
obesity in the fathers and children of the high-risk
compared with the low-risk group is compatible with
those of Glowinska et al. [34], in which children with a
family history of CVD had a higher BMI. They concluded
that in these children BMI was a great risk factor. Obesity
in boys would be significantly related to coronary artery
calcification 15–20 years later [35]. Overweight and
hypercholesterolemic children would also have more
relatives dying from CVD [36].
An important finding in this study was the increased
prevalence of diabetes in high-risk fathers and the
increased rate of IFG in high-risk children compared
with the low-risk group. A higher prevalence of hypergly-
cemia, obesity and elevated cholesterol were also
previously shown in young adults with a positive family
history of CHD [37]. IFG predicts adverse cardiovascular
events whether or not this is manifested as overt diabetes
[38]. This is usually accompanied by hyperinsulinemia
and a clustering of risk factors such as obesity,
dyslipidemia and hypertension in the childhood meta-
bolic syndrome [39]. Obese and diabetic children often
originate from the families with CVD [34]. Offspring of
diabetic parents were previously shown to be significantly
overweight, with higher rates of the development of
hyper-LDL and hyperinsulinemia over time [40].
Although we did not find any significant difference in the
prevalence of hypertension between the two groups,
some other studies have indicated that hypertension
alone may be a strong risk factor for premature CVD. For
example, Masana et al. [41] found a high prevalence of
hypertension in young adults with a familial incidence of
myocardial infarction before the age of 55 years. In
another study, a high frequency of hypertension was
found in siblings of those with premature CHD [42].
We found a generally low level of physical activity in both
high and low-risk parents and children. A sedentary
lifestyle is known to increase the relative risk of CHD
death to 1.6-fold [38], so regular physical activity should
be encouraged in all family members, especially in the
children of high-risk families to forestall CVD endpoints
in their adulthood.
The findings of this study set forth special consideration
for a household approach based on obtaining a complete
family history to identify high-risk families and to
implement preventative measures for CVD from child-
hood. In general, a significant family history of CVD is
an important risk factor for recurrence in offspring [43].
A family-based approach towards screening for CVD
would serve as a surrogate for both genetic and environ-
mental components. By this method, we can also identify
at-risk individuals within high-risk families, who can be
targeted for educational and lifestyle intervention.
Although a parental history of CVD is a useful marker for
screening, it will underestimate the number of at-risk
individuals, especially the children with hyperlipidemia.
On the other hand, many parents were still too young to
manifest coronary artery disease at the time of screening
[44–47]. Therefore we tried to expand the domain of
screening by including households containing any family
member with at least two risk factors.
Schools provide an excellent setting for introducing
comprehensive health education and promotion. This
study demonstrated that it is feasible to involve pupils to
convey cardiovascular health messages into the household
environment and to motivate participation of the
members of high-risk families in the screening pro-
gramme. Health campaigns have also shown that children
could actively influence their parents’ habits [48]. In
addition, school-based programmes that get the high-risk
parents involved with their children in learning about
CHD and its risk factors can improve the ability of the
parents to instill healthy behaviours in their children
[49].
Despite the great burden of CHD in urban communities
of Iran, screening for cardiovascular risk factors is not
performed in a systematic manner. This lack of attention,
despite its being critically important for the prevention of
CVD, may be running worldwide. The survey of families
with a history of premature CHD in Europe also showed
that screening of family members for the risk factors is
rarely performed, and 80% of patients with a positive
family historyremainundiagnosed [50]. However,
regarding the familial nature of CHD and the fact that
CHD expression is clustered in subpopulations with a
positive family history, the screening of high-risk families
can identify in a cost-effective way most of the
Household cardiovascular screening Pourebrahim et al.
233
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