Genomics|Family History|Tables|Family History and CHD

Expanding the definition of a positive family history for early-onset coronary heart disease
Scheuner, Maren T. MD, MPH^1,2; Whitworth, William C. MPH¹; McGruder, Henraya PhD, MS³
Yoon, Paula W. ScD, MPH¹; Khoury, Muin J. MD, PhD¹

Tables

TABLE 1: Characteristics of respondents with early-onset coronary heart disease and no coronary heart disease (HealthStyles 2003 Survey of Health-related Attitudes and Behaviors Among the U.S. Adult Population)

Characteristic		Early-onset CHD (n = 178) n (%)	No CHD (n = 3778) n (%)	P values^a
Female		81 (45.5)	2307 (61.1)	.002
Age group^b
	18–34y	8 (4.5)	692 (18.3)	.00004
	35–44y	16 (9.0)	28.8 (1088)	<.00002
	45–54 y	54 (30.3)	956 (25.3)	.13
	55–64 y	62 (34.8)	493 (13.0)	<.00002
	65+ y	38 (21.3)	549 (14.5)	.2
Race/ethnicity
	White	127 (71.3)	2709 (71.7)	.91
	African American	26 (14.6)	462 (12.2)	.33
	Hispanic	15 (8.4)	428 (11.3)	.23
	Asian	5 (2.8)	132 (3.5)	.62
	Other race/ethnicity	5 (2.8)	47 (1.2)	.12
More than high school education		92 (51.7)	2321 (61.4)	.18
Ever married		166 (93.3)	3268 (86.5)	.18
Income >$35,000		71 (39.9)	2195 (58.1)	.00004
Stroke onset <60 y		29 (16.3)	87 (2.3)	<.00002
Stroke onset >60 y		30 (16.9)	127 (3.4)	<.00002
Diabetes		69 (38.8)	397 (10.5)	<.00002
Obesity		52 (29.2)	631 (16.7)	.00032
Hypertension		124 (69.7)	1158 (30.7)	<.00002
Hypercholesterolemia		130 (73.0)	1190 (31.5)	<.00002

CHD, coronary heart disease; early-onset CHD, disease at or before age 60 years.
^aCorrected P values adjusted for 20 comparisons.
^bMean age (standard deviation) for early-onset CHD, 55.8 years (11.1 years)
and no CHD, 47.5 years (14.1 years) (P < .0001).

TABLE 2: Associations between various definitions of family history of coronary heart disease and early-onset coronary heart disease

Definitions of family history of CHD		Early-onset CHD N = 178	No CHD N = 3778	Prevalence OR^a for early-onset CHD (95% CI)
First-degree relatives only
	Having at least 1 first-degree relative with CHD (and no affected second-degree relative) regardless of age at onset, number, type, or lineage	53	566	3.8 (2.3–6.2)
	No family history^b	33	1701	1.0
Age of onset
	Regardless of number, type, or lineage of first-degree relatives with CHD, having at least 1 relative with:
	Early-onset CHD	33	256	5.0 (2.8–8.7)
	Late-onset CHD	12	241	2.5 (1.2–5.3)
	Early- and late-onset CHD	8	69	3.2 (1.2–8.5)
	No family history^b	33	1701	1.0
Number of affected relatives
	Regardless of age of onset, type, or lineage of first-degree relatives with CHD, having:
	1 relative with CHD	25	393	3.0 (1.7–5.4)
	>2 relatives with CHD	28	173	5.1 (2.8–9.4)
	No family history^b	33	1701	1.0
Type of affected relatives
	Regardless of age of onset or number of first-degree relatives with CHD, having a:
	Sibling with CHD	10	88	3.1 (1.3–7.3)
	Parent with CHD	30	390	3.8 (2.2–6.7)
	Parent and sibling with CHD	13	88	5.0 (2.2–11.1)
	No family history^b	33	1701	1.0
Lineage of affected relatives
	Regardless of age of onset or number of first-degree relatives with CHD, having a:
	Nuclear relative with CHD^c	10	88	3.1 (1.3–7.3)
	Maternal relative with CHD^d	10	144	2.8 (1.3–6.2)
	Paternal relative with CHD^e	18	255	3.5 (1.8–6.6)
	Maternal and paternal relative with CHD^d,e	15	79	6.2 (2.9–13.3)
	No family history^b	33	1701	1.0
Second-degree relatives only
	Having at least 1 second-degree relative with CHD (and no affected first-degree relative) regardless of age at onset, number, or lineage	20	667	2.2 (1.1–4.2)
	No family history^b	33	1701	1.0
Age of onset
	Regardless of number or lineage of second-degree relatives with CHD, having at least 1 relative with:
	Early-onset CHD	13	210	4.6 (2.1–10.3)
	Late-onset CHD	2	215	NA
	Early- and late-onset CHD	5	242	1.5 (0.5–4.3)
	No family history^b	33	1701	1.0
Number of affected relatives
	Regardless of age of onset or lineage of second-degree relatives with CHD, having:
	1 relative with CHD	5	290	1.3 (0.5–3.7)
	>2 relatives with CHD	15	377	2.8 (1.3–6.0)
	No family history^b	33	1701	1.0
Lineage of affected relatives
	Regardless of age of onset or number of second-degree relatives with CHD, having a:
	Maternal relative with CHD	5	271	1.2 (0.4–3.6)
	Paternal relative with CHD	6	205	2.3 (0.9–6.2)
	Maternal and paternal relative with CHD	9	191	3.3 (1.3–8.0)
	No family history^b	33	1701	1.0
First- and second-degree relatives
	Having at least 1 first-degree and 1 second-degree relative with CHD regardless of age at onset, number, or lineage	72	666	4.5 (2.8–7.3)
	No family history^b	33	1701	1.0
Age of onset
	Regardless of number or lineage of first- and second-degree relatives with CHD, having at least 1 first-degree and 1 second-degree relative with:
	Early-onset CHD	21	117	9.8 (4.9–19.5)
	Late-onset CHD	4	89	NA
	Early- and late-onset CHD	47	460	4.1 (2.4–6.9)
	No family history^b	33	1701	1.0
Number of affected relatives
	Regardless of age of onset or lineage of first- and seconddegree relatives with CHD, having:
	1 first- and 1 second-degree relative with CHD	8	116	3.0 (1.3–7.4)
	>3 first- and second-degree relatives with CHD	64	550	4.7 (2.9–7.7)
	No family history^b	33	1701	1.0
Lineage of affected relatives
	Regardless of age of onset or number of first- and seconddegree relatives with CHD, having:
	Maternal relatives with CHD	14	117	5.5 (2.7–11.4)
	Paternal relatives with CHD	8	124	2.9 (1.2–7.1)
	Maternal and paternal relatives with CHD	50	425	4.5 (2.7–7.6)
No family history^b		33	1701	1.0

CHD, coronary heart disease; early-onset CHD, disease at or before age 60 years; OR, odds ratio; CI, confidence interval; NA, not available (because there were too few observations to calculate).
^aAdjusted for age, race/ethnicity, marital status, education, income, self-reported obesity, hypercholesterolemia, and hypertension.
^bNo first- or second-degree relatives with CHD.
^cSibling(s) only.
^dMother only or mother and sibling(s).
^eFather only or father and sibling(s).

TABLE 3: Associations between various definitions of family history of stroke and early-onset coronary heart disease

Definitions of family history of stroke		Early-onset CHD (N = 178)	No CHD (N = 3778)	Prevalence OR^a for early-onset CHD (95% CI)
First-degree only
	Having at least 1 first-degree relative with stroke (and no affected second-degree relative) regardless of age at onset, number, type, or lineage	51	701	1.5 (1.0–2.3)
	No family history^b	81	2139	1.0
Age of onset
	Regardless of number, type, or lineage of first-degree relatives with stroke, having at least 1 relative with:
	Early-onset stroke	25	232	2.9 (1.7–5.0)
	Late-onset stroke	25	420	1.2 (0.7–2.0)
	Early- and late-onset stroke	1	49	NA
	No family history^b	81	2139	1.0
Number of affected relatives
	Regardless of age of onset, type, or lineage of first-degree relatives with stroke, having:
	1 relative with stroke	40	566	1.6 (1.0–2.5)
	>2 relatives with stroke^c	F:8 M:3	F:80 M:55	F:2.0 (0.8–4.7) NA
	No family history^b	81	2139	1.0
Type of affected relatives
	Regardless of age of onset or number of first-degree relatives with stroke, having:
	Sibling with stroke	8	53	3.2 (1.2–8.3)
	Parent with CHD	39	590	1.5 (1.0–2.3)
	Parent and sibling with stroke	4	58	NA
	No family history^b	81	2139	1.0
Lineage of affected relatives
	Regardless of age of onset or number of first-degree relatives with stroke, having a:
	Nuclear relative with stroke^d	8	53	3.2 (1.2–8.3)
	Maternal relative with stroke^e	23	276	1.6 (0.9–2.7)
	Paternal relative with stroke^f	14	287	1.2 (0.7–2.4)
	Maternal and paternal relatives with stroke^e,f	6	85	1.3 (0.5–3.2)
	No family history^b	81	2139	1.0
Second-degree only
	Having at least 1 second-degree relative with stroke (and no affected first-degree relative) regardless of age at onset, number, or lineage	22	567	1.6 (0.9–2.7)
	No family history^b	81	2139	1.0
Age of onset
	Regardless of number or lineage of second-degree relatives with stroke, having at least 1 relative with:
	Early-onset stroke	5	100	2.2 (0.7–6.6)
	Late-onset stroke	10	340	1.3 (0.6–2.7)
	Early- and late-onset stroke	7	127	1.5 (0.6–4.0)
	No family history^b	81	2139	1.0
Number of affected relatives
	Regardless of age of onset or lineage of second-degree relatives with stroke, having:
	1 relative with stroke	9	332	1.2 (0.5–2.6)
	>2 relatives with stroke	13	235	0.3 (0.1–0.9)
	No family history^b	81	2139	1.0
Lineage of affected relatives
	Regardless of age of onset or number of second-degree relatives with stroke, having a:
	Maternal relative with stroke	10	262	1.4 (0.7–3.0)
	Paternal relative with stroke	6	178	1.7 (0.7–4.4)
	Maternal and paternal relative with stroke	6	127	1.4 (0.5–3.9)
	No family history^b	81	2139	1.0
First- and second-degree relatives
	Having at least 1 first-degree and 1 second-degree relative with stroke regardless of age at onset, number, or lineage^c	F:19 M:5	F:246 M:125	F:2.4 (1.3–4.4) M:0.7 (0.2–1.8)
	No family history^b	81	2139	1.0
Age of onset
	Regardless of number or lineage of first- and second-degree relatives with stroke, having at least 1 first-degree and 1 second-degree relative with:
	Early-onset stroke	0	34	NA
	Late-onset stroke	5	114	1.1 (0.4–3.0)
	Early- and late-onset stroke^c	F:15 M:4	F:105 M:73	F:3.1 (1.6–6.1) NA
	No family history^b	81	2139	1.0
Number of affected relatives
	Regardless of age of onset or lineage of first- and seconddegree relatives with stroke, having:
	1 first- and 1 second-degree relative with stroke	6	130	1.2 (0.5–2.9)
	>3 first- and second-degree relatives with stroke	F:13 M:5	F:158 M:83	F:2.5 (1.2–5.2) M:0.9 (0.3–2.4)
	No family history^b	81	2139	1.0
Lineage of affected relatives
	Regardless of age of onset or number of first- and seconddegree relatives with stroke, having:
	Maternal relatives with stroke	2	108	NA
	Paternal relatives with stroke	8	65	2.7 (1.1–6.3)
	Maternal and paternal relatives with stroke	2	108	NA
No family history^b		81	2139	1.0

CHD, coronary heart disease; early-onset CHD, disease at or before age 60 years; F, female; M, male; NA, not available (because there were too few observations to calculate).
^aAdjusted for age, race/ethnicity, marital status, education, income, self-reported obesity, hypercholesterolemia, and hypertension.
^bNo first- or second-degree relatives with stroke.
^cSignificant interaction between sex and family history (P < .05) was found, and interaction term was included in the regression model.
^dSibling(s) only.
^eMother only or mother and sibling(s).
^fFather only or father and sibling(s).

TABLE 4: Summary of significant associations between family history and early-onset
coronary heart disease

Family history definitions

≥1 first-degree relative with early-onset CHD

≥1 first-degree relative with late-onset CHD

1 first-degree relative with CHD at any age of onset

≥2 first-degree relatives with CHD at any age of onset

≥1 sibling with CHD at any age of onset

≥1 parent with CHD at any age of onset

Parent and sibling pair with CHD at any age of onset

Maternal first-degree relativesa with CHD at any age of onset

Paternal first-degree relativesb with CHD at any age of onset

Maternal and paternal first-degree relatives^{a, b} with CHD at any age of onset

≥1 second-degree relative with early-onset CHD

≥2 second-degree relatives with CHD at any age of onset

First- and second-degree relatives with CHD at any age of onset

≥1 first-degree relative with early-onset stroke

≥1 sibling with stroke at any age of onset

First- and second-degree relatives with stroke at any age of onset^c

≥1 first-degree relative with diabetes^c

CHD, coronary heart disease; early-onset CHD, disease at or before age 60 years;
late-onset CHD, disease after age 60 years.
^aMother only or mother and siblings.
^bFather only or father and siblings.
^cSignificant association among women only.