JACC Vol. 12. Xo. 5
November 19RR:127; 8o
1273
EPIDEMIOLOGIC STUDIES
Risk Factors in Siblings of People Wit
Heart Disease
reammature
Coronary
DIANE M. BECKER, ScD, MPH,* LEWIS C. EECKER, MD, FACC,t
THOMAS A. PEARSON, MD, PHD.*$ DAN J. FINTEL, MD, FAX,? DAVID M. LEVINE MD,*
PETER 0. KWITEROVICI-I, MD4
Baltimore, Maryland
Prior studies of the contribution of coronary disease risk
factors to familial aggregation of premature coronary disease may have underestimated risk factors by relying on
self-reported risk factor prevalence levels or, when risk
factors have been measured, by using cut points in excessof
the9Otb percentile. To determine the actual prevalenceof
hyperlipidenda, hypertension and diabetes, and the awareness of these coronary risk factors in unaffected family
members, 150 apparently coronary disease-free sibling of
86 people who had documentedcoronary dise@e before 60
years uf age were studii. LUI subjects participated in a I
day screetig preceded by a self-administered risk factor
questhnmaire and a m
interview. Participation of
both the b&x patients
and sibtings exceeded 86%.
With the use of nationally established recommendations
for bbod pressure and lipids, which are based on coronary
dii
risk curves, scmning revealed that 48% of brothers and 41% of sisters were hypertensive,45% of brothers
and 22% of sbters bad a lipid abnormality, 38% of siblings
Coronary heart disease has long been shown to cluster
significantly within families. First degree relatives of probands who had coronary heart disease events before 60
years of age exhibit a risk ofpremature
coronary disease that
is 2 to 12 times that of the general population (I-6).Considerable controversy exists concerning the relative indepen-
.
Fmm the Divisions of ??
lntemaI Medicine and tCardioloav.
I~. Department of
Medicine; flhe Lipid Research Clinics. Department of Pediatrics; and Uhe
Deoartment of Euidcmioloav. The Johns Hookins Medical Institutions, Baltin&e. Maryland. This study was supported in part by Preventive CardioIagy
Academ;: Award No. KO7HLOI 13 and Grant No. RRllUOJ5 CLINFO (for
Computational assWnce) from the National Institutes of Health, Bethesda,
from the DuPont Corporation. North Bilkrica, MassaMaryland and a @nant
chusetts.
Manuscript received January 8,1988; revised
manuscript received May 5.
1988, accepted June 3, 1988.
A&&&r@&
Diane M. Reeker, ScD. MPH, Preventive Cardiology Promms, The Johns Hopkins Hospital, 1830 East Monument Street.
Baltimore, Maryland.
01988 by the Americnn College of Cardiology
were current cigarette smokers and 4,?‘% were d&&tic.
Two or more risk factors were present in 42% of bro&ers
and 25% of sisters. More than 75% of siblings had ooe or
more risk factors that woukl require iatervent&L Whea
compared with a race-, gender- and age-matched referem
population from the Lipid ResearchClinks Prevateace
Study, distributiowsfor b&d presses and for tetal &HI
low density lipoproteb~cb&steral were Mgber for the
Gbliags in every gender SHI age group. !Sibli&gs were
generally unawareoithepresenceofriskfaetars,oZdy43%
of hypertensive siblii
and 27% of si
with @id
abnormalities were aware of these risk factors.
PreGously u&tected risk factors were highly prevatent
in sibiiigs of pe@e witb premature comzary d&ease.
These data support cnrreH naGonal recommer&lat&msfor
comprehensive risk factor screen& io this fSs@ i&?&i.
able high risk fw
group.
(J An Cdl Cardial19&?;12:1273-80)
dent contribution of unexplained genetic factors and known
coronary heart disease risk factors that aggregate within
families. Many investigators (7-11) contend that a positive
family history remains the most important independent
predictor for premature coronary heart disease, whereas a
few (12,131 suggest that the major portion of familjaiclustered coronary heart disease can be attributed to in,‘lerited and environmental risk factors. A recent review of
methodologic issues in family studies (14) nu!ed that one
problem in the majority of prior studies is the reliance on
self-reporting or reporting by other relatives of the presence
or absence of risk factors in family membersof coronary
heart disease probands.Another common problem in prior
studies is the use of blood pressure and lipid cut points that
exclude values that have been shown fo be associated with
increased risk of coronary disease.
The existing studies, focusing predominantly on epidemi0735-1097/W13.50
1274
BECKGR El AL.
CORONARY RISK FACTORS
IN FP
‘LIES
ologic issues, may leave the clinical community confused
about the importance of screening for remediable risk factors
in families. The objectives of this study were I) to determine
the true prevalence of modifiable coronar)’ heart disease risk
factors including hypertension, hyperlipidcmia, diabetes and
cigarette smoking using contemporary guidelines, and 2) to
determine the awareness of the presence of potentially
modifiabie risk factors in apparently healthy aduk siblings of
people with documented coronary heart disease. Further,
this study provides the first empirical estimates in the United
States population of the yield of multiple risk factor screening in unaffected siblings soon after a premature coronary
heart disease event in a young brother or sister.
Methods
Index coronary heart disease patients. Index patients
were eligible if they had a documented coronary disease
event before 60 years of age. The majority (93%) of participating index patients were identified between January 1983
and June 1986 during a coronary heart disease hospitalization. An additional 7% were identified in a cardiac rehabilitation program after a recent coronary heart disease event.
All but two had angiographicdily documented coronary
disease; these two patients had sllstained a documented
myocardial infarction. The mean age of index patients was
49 + 1I years; 83% were male. Risk factor distributions were
not analyzed in index patients becalrse 6% had experienced
coronary disease events before the hospitalization. TLese
patients were receiving anti-ischemic medications that po
tentially confound risk factor prevalences and awareness. Of
90 eligible index patients, g6 (95%) provided access to
siblings.
Asymptomatic siblings. The 86 probands yielded 172
asymptomatic biologic siblings 30 to 59 years ofage (mean 45
2 7.5); 51% were male and 99% were white. The majority
(78%) were high school graduates and 20% were colleie
graduates.
All siblings c60 years of age without known coronary
heart disease, as determined by telephone interview with
verification by the physician of record, were invited for a
cardiovascular history, physical examination and laboratory
evaluation. Of 172 eligible GbIings, I50 (87%) participated in
the screening evaluation, which was performed an average
of 2 months (range 2 weeks to 4 monrhs) after hospital
discharge of the index patient. The majority (19) of the
remaining 22 siblings cited geographic distance from the
screening site as the reason for refusal.
Screening protocol. A self-administered
questionnaire
was mailed to siblings before the screening appointment to
elicit self-reporting of the presence or absence of hypertension, hyperlipidemia, diabetes, cigaret!e smoking and curren: and past medications and illnesses. These items were
again elicited in a personal interview by a research nurse just
JACC Vol. 12. No. 5
Novcmbcr 1988: 1271-80
before the screening examination (see Appendix). The sibling was considered aware of the presence of a risk factor if
he or she indicated “possibly yes” or “yes” to the elicited
risk factor information either on the questionnaire or during
the interview.
Physical examination and laboratory evaluation. AII siblings received a history and physical examination by a
cardiologist according to a standardized protocol. Bloqd
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1276
BECK-R
ET AL
COR&ARY
RliK
IACC Vol. 12. No. 5
FACTORS
November IYRll:l273-80
IN F4MILIES
iences and awareness were aimosi identical across ail years
of the study.
Cigarette smoking (Table5). The overall prevalence of
current smoking was 38%. The prevalence of smoking in
each age group was similar for brothers and sisters. Although brothers appeared to smoke more cigarettes/day than
did sisters, this difference was not statistically significant.
Again, the prevaiences were approximately equal by study
year, with slightly fewer brothers (36%) smoking in 1986.
Diabetes or KG abnormali&.
A history of diabetes was
given by three sisters and two brothers. An additional
brother and one sister had a fasting glucose level ~130 mg/
di. which was verified with abnormal glucose tolerance
results. The overall prevalence of diabetes was 4.7%; two
siblings (2%) were unaware. Ail self-reported siblings had
received treatment.
No sibling had evidence of a prior myocardiai infarction
or of myocardiai ischemia on rest ECG. Left ventncuiar
hypertrophy by voltage criteria was present in three siblings
who were also hypertensive.
Multiple risk factors (Fig. 3). In analyzing the prevalence
of combinations of risk factors, diabetes was not included
because ail diabetic subjects also had one or more of the
three major risk factors. Of the total, 117 (78%) had one or
more risk factors. The overall prevalence of risk factors was
higher in brothers (83%), than in sisters (73%). Only 17% of
brothers were free of risk factors, whereas 27% of sisters
were without risk factors.
A
Figure 1. Hypertension
classification
in siblings according to the
Joint National Committee
on High Blood Pressure recommendation
(A, brothers; B. sisters). Numal
= diastolic blood pressure < 85 mm
Hgand systolic blood pres=ure c I40 mm Hg; high normal = diastolic
blood pressure 85 to 89 mm Hg; mild hypertension = diastolic blood
pressure 90 lo I04 mm Hg; moderate hypertension = diastolic blood
pressure I05 to I I4 mm Hg; severe hypenension
= diastolic blood
pressure 2 I5 mm Hg: borderline isalated systolic hypertension =
140 to 159 mm Hg; isolated systolic hypertension = 2160 mm Hg.
Discussion
BI~IMI pressure. The cut points of 140 mm Hg for systolic
and 90 mm Hg for diastolic blmd pressure were selected to
define hypertension not onty because these levels correspond with the Joint National Committee on High Blood
Pressure classification but because they represent levels in
the coronary heart disease risk curves where the slope of
risk increases sharply (23). The few prior family studies
(5.25,26) that measured blood pressure in siblings reported a
I
screening, with 73% of hyperiipidemic brothers and 75% of
hyperiipidemic sisters unaware of lipid elevations. (Table 4).
There were no time trends in the prevalence of hyperiipidemia or in awareness based on self-reporting by year, Preva-
Table 3. Plasma
Lipid
Distribution
of IS0 Siblings
of 86 Premature
Coronary
Heart
Disease
Probands
Brothers (age. yr)
Total cholesterol
295th pcrcer.tile*
zY@th prcentile*
Mean lotal cholesterol (mgldl)
LDL choleskrd
~75th pxcentile*
z9nh percentile’
Mean LDL choltsterol (mddl!
-.
Sisters (age, yr)
30 IO 39
(n = 24)
40 IO 49
(n = 32)
50 IO 59
(II = 21)
Total
(n = 77)
30 IO 39
(n = 16)
40 to 49
In = 291
50 to 59
(II = 28)
Total
(II = 73)
38%
33%
226 r 58
38%
19%
223 2 38
43%
1%
230 + 4s
39%
23%
226 k 49
44%
31%
209 ? 51
31%
17%
207 c 41
2%
II%
229 f 36
33%
18%
215 k 42
38%
21%
44%
22%
40%
20%
41%
24%
147 i: 56
148 f 40
IQ c 43
21%
Ii%
139 + 35
27%
14%
131 2 41
!I%
I50246
44%
19%
130 f 53
(4%
124 I 34
??
T’hc Lipid Research Clinics Prevaleitce Study raw-. gender- and age-specific reference population percentiles. LDL = low denshy lipoprotein=, (20).
JACC Vol. 12, No. 5
Novcmbcr 19tWl27FRo
Table 4. Awareness
Premature Coronary
CORDNARY
of Hyperlipidemia
in 150 Siblings of 86
Heart Disease Probands
Present
Self-report of hyperiipidemia
Yes
Absent
dias!olic
SkIerr
Precent
Abrenr
9
‘Hyperlipidemia = low density lipoprotein cholesterol ~I60 mddl. or
triglycerides 2250 mg/dl or receiving lipid-lowering drug treatment.
lower prevalence of hypertension, approximately 20%. most
likely because blood pressure cut points were set excessively high, above the 90th percentile or >I60 to 170 mm He
systdlic and >I@0 to 110 m-m Hn diastolic level. When both
the Lipid Research Clinics Prevatence Study reference population percentile distributions and risk-gssociated i984
guidelines of the Joint National Committee on High Blood
Pressure are used. it is clear that brotbnrs and sisters of
patients with documented coronary arterv disease before aee
60 have a high prevalence of b&d pressure levels that aYe
Figure 2. The prevalence of lipid abnormalities in siblings according to the National Cholesterol Education Program Adult Treatment
Gr::‘zlines
and the Triglyceride
Consensus Conference
Guidelines
(A, brothers: B, sisters). High risk low density lipoprotein cholesterol = ~160 mg/dl; low high densiiy lipoprotein cholesterol = 535
mgldl;
high triglycerides
= 5250
mgMl.
1277
associated with increased coronary heart &sea% risk and
may require medical evaluation and treatment. Brothers had
a greater prevalence
of hypertension
and of “high normal”
Hyperfiprdem,.a cm Scre-nmg”
Brothers
BECKER ET AL.
RISK FACTORS IN FAMILIES
fied
blood
as having
pressure.
“normal”
Only
31%
pressure
of brothers
on the
were
average
classiof three
taken several hours apart. of these. 5%
were already receiving antihypertensive treatment, yielding
only 26% “true normal” subjects among brothers.
The majority of brothers and almost hal of the sisters
were unaware of blood pressure elevations. A potential
problem in analyzing the awareness data in our study is the
studies and national initiatives
proliferation
of rewch
targeting blood pressure education for both the general
population and physicians between 1983 and the present.
There is no evidence from our study to sugest that hypertension detection in the sibling group had markedly improved between
1983 and 1986. it is unlikely that the
prevalence of hypertension
in siblings was decreasing over
the years of the study or that it is significantly lower at this
time. However,
new initiatives of the National High Blood
Pressure Education Program may result in improved detection of high blood pressure in the coming years.
Plasma lipids. The LDL cholesterol cut point of 160 mg/
dl was used to define hvpercholesterolemia
on the basis of
the National Cholesterol Education Program’s Adult Treatment Guidelines. Coronary heart disease risk curves demonstrate a sharp increase in the slope of risk at total
cholesterol levels of 240 mg/dl, which correspond approximately to an LDL cholesterol cut point of 160 mg/dl
!21,23,24). Although triglyceride elevations have not been
independently associated with coronary disease In most
studies, levels of 2250 mgldl classified as elevated in this
study represent the approximate !Mth percentile for the
sibling age groups in this study. Airhough only a small
percentage of brothers (6.5%) and sisters (1.4%) were considered to have abnormal lipids solely on the basis of
triglyceride levels, including those siblings as hyperlipidemic
may be justified
because
d the increased
likelihood that
trigiyceride elevation in the sibling sample represents familial combined hyperlipoproteinemia,
which is associated with
a macke~~ly increased coronary heart disease risk (27). “High
risk” L:IL cholesterol was the most frequent abnormality
cb+ KQ *II both men and women. As with hypertension,
abnormai lipids were more common in brothers than in
sisters with 54% and 78%. respectively. exhibiting desirable
lipId patterns on screening.
twareness of elevated lipid levels was low in both
brci5ers and sisters with 73% unaware. The National Chelesterol Education Program physician initiatives tPegan in
1987 with publication of the Adult Treatmen! GuiMines.
Improved practice patterns and increased public education
efforts may improve awareness of elevated lipid levels in the
future. Data from this study suggest. however, that sign&
cant awareness changes did not occur between 1983 and
rest measurements
1278
BECKER ET At.
CORONARY RISK FACTORS
Table 5. Smoking
Prevalence
JACC Vol. 12. No. 5
Novcmbcr 19llR:127340
IN FAMILIES
end Number
of Cigarettes
in 150 Siblings of 86 Premature
Coronary
Current smokers (5%)
Number of
40 IO 49
Heart
Disease
Prabands
Sisters (age. yr)
Brothers (age. yr)
30 to 39
(n = 241
(n = 32)
so to 59
tn = 21)
Total
tn = 77)
30 to 39
In = WI)
40 IO 49
tn = 29)
50 IO 59
(n = 28)
(n = 73)
42
17 r 29
44
18 + 27
29
21 238
39
19 + 31
38
8 f I2
41
I6 ? 25
32
12 f 24
37
13 f 22
Told
cigarettes per day
1986. This finding is further substantiatedby data from the
National Institutes of Health Cholesterol Awareness Surveys of both the gergeralpublic and physiciansin 1983 and
1986, which dernol;c!mred only modest changes in the
number of people who had blood cholesterol levels checked
and no increase between 1983 and 1986 in the number of
people who were told that cholesterol levels were elevated
(28,29).
Cigarettesmoking. The prevalence of current smoking in
both brothers and sisters was higher than the 27 to 30% of
the general population who smoked cigarettes during the
sibling screening period, 1983 to I986 (30). Prior studies
(26,311 in high risk families have reported a wide range of
smoking prevalence levels in sisters (I5 to 53%) and consist-
Figure3. The prevalence
of major risk factors in siblings (A,
brothers; 8, sisters). Lipid abnormality
= low density lipoprotein
cholesterol B 160 mg/dl. or triglycerides
250
mg/dl or on a lipidlowering drug; hypertension
= blood
pressure 2 140190 or on antihypertensive drug: smoking = current regular cigarette smoker.
FACTORS
!X?U
P
ent levels of approximately45% in brothers. Most of these
studies have not been done in the American population.
Although in our study the prevalence rates were similar in
brothersand sisters, brothers appeared to be heavier smokers. Given that there is evidence of a multiplicative interacties between cigarette smoking and family history of’ early
coronary disease (32,33), it is likely that smoking prevalence
alone does not reflect the true importance of smoking as a
risk factor in the sibling population. The validity of selfreporting was not examined, but prior studies (35) suggest
that the bias is in favor of underreporting, possibly related to
a perception of social undesirability.
Diabetes.
The reported diabetes prevalence of 4.7%
agrees with prior studies in families with coronary heart
disease, which have shown a prevalence rate of I to 5%
(26,31). Although this was a low frequency risk factor, a
small number of siblings with probable diabetes were unaware of their condition.
MuMpIe risk factors. The majority of brothers and sisters
had at least one of the major risk factors for coronary heart
disease. It is possible that other more recently reported
familial risk factors, such as abnormal piatelet activation (32)
and apolipoprotein abnormalities (35), may be prevalent in
those siblings who appear “normal” on screening. As it is
generally agreed that premature coronary heart disease is of
multifactorial origin, it is not surprising that such diverse risk
factor patterns exist in high risk families. Male siblings
clearly have a higher prevalence of all risk factors; 42%
exhibited two or more of the three major risk factors.
Conclusions. This study demonstrates that the age-, gender- and race-adjusted distributions of blood pressure and
plasma lipids are considerably higher in clinically unaffected
siblingsof peopie Gth premature coronary heart disease
than in a general reference population. The majority of
siblings have one or more risk factors as assessed by
contemporary nationally established guidelines for determining risk levels of blood pressure and plasma lipids; further,
mer;y were uMware of the presence of potentially modifiable
risk factors. Because high risk families such as these account
for >50% of coronary heart disease before 55 years of age
i36.37). intensive efforts should be made to identify and alter
modifiable risk factors. This study provides empirical support for recent recommendation of the National Cholesterol
Education Program (21) that physicians provide comprehen-
JACC Vol. 12. No. 5
1279
Novcmbcr tY%l273-so
sive risk factor screening to people
premature coronary disease.
with a family history of
Appendix
-.-
Items Used
to Elicit Self-Report of the
Presence of Risk Factors
1. Have
a.
b.
c.
d.
you ever had any of the foilowing
your
your
your
your
blood
blood
blood
btood
8. Nor:? ‘J. !.nflvRcr RH. Spangler RD. Noct AH. Kimberling WI. Generic
~p~denrologic PW+IYof ezy-ooser ~rehemx heart disease. CirculaliL%
IYao:hl 503-x.
RESPONSES:YES.NO, POSSIBLY
YES,
NOT
SURE
For each item, if “YES”
or “POSSIBLY
YES,”
responiients
were asked to give the level if known. indicate if the ievel was
“NORMAL”
or “HIGH,”
indicate the approximate date and the
source of information.
a.
b.
c.
d.
on any occasion
in your
high blood pressure?
_
high blood cholesterol?
high blood triglycerides?
diabetes or a high blood sugar?
RESPONSES:
YES,
NO,
life. had any of the
__
POSSlBLY
_
YES,
NOT
SURE
For each item, if “YES’ or “POSSIBLY
YES,” the respondent
was asked to name the approximate
date, duration, source of
information, level if known and specific treatment.
3. Have
you ever
conditions:
a.
b.
c.
d.
taken
any
medicine
for any of the foilowing
9. Snowden CB. McNzmara PM Garrixm RJ. Fei&tb hi. Kannel WB.
Epstein Ft!. Predicting sor?nary heart &i:ebxe in shlinp: a mt’lriv~;mte
dxe$$mect. Am J Epidemiol I%2:!15:?IF??.
111 ten Kate LP. Boatman H. Da&r 5P. Mocat~ky AG FamdrJ qge@;rrmn
of coronary heart d1sea.z and it\ re;alicr! lo krmwr: genettc rirk factors.
Am J Cardlol IW?$&94>53.
l I. Shea S. Ottman R. Gabrieli C, Srega ?,. Nichoh A. Family hlrrq a=. an
mdependent ri?k factor for coronary &III
,%zxe J Am Co11 C+rdiol
lY84:1:793-$nl.
12. R~:xmen AM. Nikkill EA. Aggrcp!ilm of coronary risk iactors in
hmdler of men wrth fatal and non-fatal coronary hean diseaw. Zr Heail
J 1979:4?~37340.
13. Gold~lem JL. Hazzard WR. Schn,.; HG. Bierman EL. Motul&y AG.
Lipid level? in 500 rurvlvors rrf myocardial miarcliun. J Clin inwd
lY73:52~I53.~3,
14. Perkms KA Family history of coronary heart disease: ir it dn indepndent risk fx:or? Am J Epidcmiol 19&;!24:182-93.
15. Central Patient Registry and Coordinating Center for the Lipid Rerearch
Climcx Reference Manual for the Lipid Research Clinics Prevalence
Chapel Hill: University of North Carolina. 1974.
Sludy. Vol.
I and
2.
high blood pressure’!
high blood cholesterol?
high blood triglycerides?
diabetes or a high blood sugar?
RESPONSES:
.I! diagnouls. Am J Cardiol lvl%.44:6&6.
levels checked:
pressure?
cholesterol?
triglycerides?
sugar?
2. Have you ever,
foltowing:
6. Rirsancn AM. FamrhaIoccurrence afc0ron-q
YES,
NO,
16. Repon of The Joint National Committee on Detection. Evatuation and
Treatmen of High Blood Pressure. Arch lnlem Med lY84;144:!U45-57.
17. Rose G. Ellackbum H. Cardiovascular Survey Metho&.
Orgmlration Monograpn Series No 56 i%.
POSSIBLY
YES,
NOT
SURE
For each item, if “YES”
or “POSSIBLY
YES,”
respondents
were asked IO give the name of the drug if known, I!K type of
drug if hnown, the duration of use and the medical care source.
“NOT SORE” responses were probed and respondents were offered the opportunity
to elucidate any potential occasion on which
the risk factor may have been present, even if transiently.
AWARE
= “YES” or “POSSIBLY YES” TV item 2 or a response
10 Item
that categorized the number as “HIGH
,” or a response on
item 3 that indicated a “YES”
or “POSSIBLY
YES”
to drug
treatment for the specific risk factors.
I
World Heabh
18. Manual of Laboratory Opetalioes. Lipid Rerearch Clinic% Progam: ‘Jot.
I: Lipid and Lipoprotein Analysis. Belhetda. Maryland: Natiowal Institutes of He&h. NIH Publication 75-628. 1974.
19 Friedewald WT. Levy RI. Frcdickwn DS. Estimation of the concentratmn of low-denshy lipoprobzin cholesterol in plasma without use of the
prepanrivc uhrdcemrifuge. Clin Clem 197?;!8:499-502.
20. The Lloid Research Clinics Powlation Sludies Data BoJk: Vol. I: The
Preval&ce Study. Bethesda, #arylanJ: National Indllutes of He&h,
NIH Publication No. 80-1527, 1980.
?I. Experl Panel. Nalional Cholesterol Educabon Program. Expert panel MI
detection. evalualion and treatment of high blood cholesterol in adults.
Arch Intern Med 19811;11:3f&9.
22. Conrensus Conference:
1984;?Sl: t 19f+200.
Trealmenl
of hypertriglyceridemia
JAMA
’
References
I. Rose G.
23. M&n JJ. Hulley SE. Browner WS. Kuller H. Wenworth 0 Serum
choleqterol. blood pressure and mortality: rmplic~lions from a cohort of
361.662 mep. Lance1 19&X:933-6.
heart disease. Br J Prev Sue Med
14. Kannel WB. McGee D. Gordon T. A general cardiovascular risk p-ofile:
the Fmmmgham Study. Am J Cardiol 19%x38:4&51.
2. Slack J, Evans KA. The increased rirk of death from ischemic hedr!
discabe in first degree relatives of I!1 men acid 96 wmcn \vith irchemic
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myocardial infarclian. Dan Med Bull lY~?~l0:25%62.
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1964:18:75-%0.
1280
BECKER ET AL.
CORONARY RISK FACTORS
IN FAMILIES
JACC Vol. 12. No. 5
November 198li:12734l
26. Hamsten A. de Faire U. Risk factors for coronary artery disease in families
of young men with myocardial infarction. Am J Cardiol 1987;59:14-9.
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27. Goldstein JL, Schrott HG, Hazzard WR, Bierman EL, Molukcy AG.
Hyperlipidemia in coronary heart disease !i. Genetic analysis of lipid
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smoking for coronary prone families in Utah. West J Med 1984:141:196202.
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cholesterol and heart disease, JAMA 1987;258:3327-35.
30. Centers for Disease Control. Cigarette smoking in the United States 1986.
MMWR 1987:36:582-S.
31. Rissanen AM. Familial occurrence of coronary heart disease according to
clinical manifestation. Acta Med Stand 1985;218:355-63.
32. Fuster V. Cheseboro JH, Frye RL. Elveback LR. Platelet survival and
the development of coronary artery disease in the young adult: effects of
34. Brockway BS. Chemical validation of self-reported smoking rates. Behav
Ther 1978;9:685-6.
35. Freedman DS, Srinivasan SR, Shear CL, Franklin FA, Webber LS,
Berenson GS. The relationship of apolipoproteins A-l and B in children to
parental myocardial infarction. N Engl J Med 1986;315:721-6.
36. Williams RR. Understanding genetic and environmental risk factors in
susceptible persons. West J Med 1984:141:799-6&
37. Williams RR, Hasstedt SJ. Wilson DE, et al. Evidenct :!x: xi: oi:h
familial hypercholestcrolemia can avoid early coronary death: an anarysis
of 77 gclle carriers in four Utah pedigrees. JAMA 1986:255:2l%24.