Follow up after a family based genetic screening programme for familial hypercholesterolaemia: is screening alone enough?

Familial hypercholesterolaemia is an autosomal dominant disorder of lipoprotein metabolism, with an estimated frequency of 1 in 500 in Western countries; it results in excess mortality from coronary artery disease.¹ Now that the genetic defects can be detected and statins are available to lower lipids effectively, genetic screening has been considered.^2–3 In 1994 a family based genetic screening programme for familial hypercholesterolaemia started in the Netherlands. The programme's effectiveness rests on the evidence based treatment of newly identified patients. We therefore assessed the subsequent preventive care and short term clinical outcome in people testing positive for familial hypercholesterolaemia as a proxy for the expected long term level of coronary artery disease.⁴

Participants, methods, and results

The foundation for tracing hereditary hypercholesterolaemia performs cascade screening in families of patients with clinically diagnosed familial hypercholesterolaemia with a known mutation, actively approaching first degree and second degree relatives.⁵ Family members are tested for the known mutation; their cholesterol level is not measured. The test result is communicated only to the person screened (by mail). The foundation is not involved in subsequent treatment or in monitoring follow up.

We conducted the evaluation study from March to September 1998 in all 215 people who tested positive from a consecutive cohort of 677 people screened as part of the programme. The inclusion criteria were consent to genetic testing and the current study, a positive test result, and age 18 or over.

We collected data with three self administered questionnaires—at screening and at 7 months and 18 months after communication of the test result. The main outcome measures were quality of treatment according to the key recommendations of the Dutch guidelines on hypercholesterolaemia and quality of clinical outcome by achieved cholesterol level, body mass index, and smoking status (table).⁴

We divided the people testing positive into two categories: those with an unknown cholesterol concentration or with normal cholesterol without treatment at the time of screening (“newly identified cases”) and those known to have hypercholesterolaemia (cholesterol ⩾6.5 mmol/l) or being treated for this condition (“confirmed cases”).

One hundred and sixty six (77%) participants filled out all three questionnaires. Respondents and people lost to follow up differed in only one characteristic—use of statin (57% v 39%, P<0.05).

Seventy three (44%) respondents were men, 41 (25%) were newly identified, and 125 (75%) were confirmed cases. The confirmed cases were older (48.2 v 38.9 years), had higher cholesterol concentrations (10.7 v 6.0 mmol/l), if known, and were more likely to have at least one first degree relative with cardiovascular disease (62 (50%) v 13 (32%)) or one premature cardiovascular death in the family (26 (21%) v 2 (5%)) (P<0.05 for all comparisons).

Although the quality of treatment and clinical outcome improved substantially over time in both groups (table), people testing positive for familial hypercholesterolaemia did not attain an optimal level of care. Quality of treatment was still unsatisfactory in 33 (20%) cases, and quality of clinical outcome was still insufficient in 75 (45%). Fifty eight (35%) participants were hypercholesterolaemic at follow up, nine (16%) of those with hypercholesterolaemia did not take statins, and 40 (24%) participants smoked.

Comment

Both confirmed and newly identified patients benefit from screening for familial hypercholesterolaemia, as their risk status improves and cholesterol lowering treatment is instituted, but in almost half of all cases the achieved level of care does not keep up with current guidelines. Opportunities for improvement towards current guidelines include physician education, better implementation of guidelines, and, especially, an intensification of the link between diagnosis and follow up care in the screening process.

Table.

Quality of treatment and clinical outcome in people testing positive for familial hypercholesterolaemia. Values are numbers (percentages)

	Newly identified cases (n=41)			Confirmed cases (n=125)
	At screening	At follow up		At screening	At follow up
Follow up	NR	34 (83)		NR	107 (86)
Cholesterol checked	17 (41)*	29 (71)*		125 (100)*	93 (74)*
Use of drugs	0*	14 (34)*		99 (79)*	113 (90)*
Use of statin	0*	14 (34)*		95 (76)	102 (82)
Diet	5 (12)*	19 (46)*		87 (70)	94 (75)
Lifestyle advice	0*	34 (83)*		41 (33)*	107 (86)*
Quality of treatment:†
Good	10 (24)	20 (49)		31 (25)	74 (59)
Moderate	0	4 (10)		58 (46)	27 (22)
Unsatisfactory	31 (76)	16 (39)		30 (24)	17 (14)
Missing	0	1 (2)		6 (5)	7 (6)
Known hypercholesterolaemia	0*	10 (24)*		124 (99)*	48 (38)*
Cholesterol unknown	31 (76)*	9 (22)*		0*	8 (6)*
Smoking	14 (34)	12 (29)		30 (24)	28 (22)
Body mass index >27 kg/m2	3 (7)	4 (10)		33 (26)	30 (30)
Quality of clinical outcome:‡
Good	5 (12)	15 (37)		1 (1)	34 (27)
Moderate	5 (12)	6 (15)		0	31 (25)
Unsatisfactory	31 (76)	19 (46)		124 (99)	56 (45)
Missing	0	1 (2)		0	4 (3)

NR=not relevant. 

^*Significant difference in time (P<0.05). 

^†Good=use of statin (depending on cholesterol level), adherence to diet, and advice to quit smoking and lose weight if necessary; moderate=use of statin, without diet or appropriate lifestyle advice; unsatisfactory=no drugs while hypercholesterolaemic, or using cholesterol lowering drugs other than statins. 

^‡Good=cholesterol <6.5 mmol/l, body mass index ⩽27 kg/m², and non-smoker; moderate=cholesterol <6.5 mmol/l and body mass index >27 kg/m², smoker, or both; unsatisfactory=cholesterol ⩾6.5 mmol/l or unknown, regardless of body mass index or smoking status.