Table 2.

NICE recommended criteria performance (detection rate, sensitivity, specificity, PPV, NPV, AUC) for identifying monogenic FH (n=260)

Threshold for the various case-finding tools	FH positive above threshold	FH positive below threshold	Detection rate	Sensitivity (95% CI)	Specificity (95% CI)	PPV* (95% CI)	NPV* (95% CI)	AUC (95% CI)
FAMCAT 1 (at 0.140 threshold)	5/18	11/242	27.8% (12.5%–50.9%)	31.2% (11.0% to 58.7%)	94.7% (91.1% to 97.1%)	25.8% (12.8% to 45.2%)	95.9% (94.4% to 97.0%)	0.63 (0.51 to 0.75)
FAMCAT 2 (at 0.0047 threshold)	11/24	5/236	45.8% (27.9%–64.9%)	68.8% (41.3% to 89.0%)	94.7% (91.1% to 97.1%)	43.4% (28.3% to 57.4%)	98.1% (96.1% to 99.0%)	0.82 (0.70 to 0.94)
Simon-Broome Possible FH (TC >7.5 mmol/L or low-density lipoprotein cholesterol >4.9 mmol/L and family history premature CHD+)	9/80	7/180	11.3% (6.0%–20.0%)	56.3% (29.9% to 80.2%)	70.9% (64.8% to 76.5%)	10.3% (6.7% to 15.3%)	96.5% (94.0% to 97.9%)	0.64 (0.51 to 0.76)
Dutch Lipid Clinical Network Criteria Score ≥6 points (Probable FH)	6/17	10/243	35.3% (17.3%–58.7%)	37.5% (15.2% to 64.6%)	95.5% (92.1% to 97.7%)	33.0% (17.5% to 52.5%)	96.3% (94.7% to 97.4%)	0.66 (0.54 to 0.79)
TC >9.0 mmol/L (≥30 years) OR TC >7.5 mmol/L (<30 years)	7/25	9/235	28.0% (14.3%–47.6%)	43.8% (19.8% to 70.1%)	92.6% (88.6% to 95.6%)	26.0% (14.8% to 40.9%)	96.5% (94.8% to 97.7%)	0.68 (0.56 to 0.81)

Detection rate.

*PPV and NPV assumes a prevalence of FH of 0.056 based on study.

†Premature defined as coronary heart disease <50 years in second-degree relative or <60 years in first-degree relative.

†95% CI calculated using the Wilson score interval discussed in Brown, LD, Cat, TT and DasGupta, A (2001). Interval Estimation for a proportion. Statistical Science 16:101–133.

AUC, area under the curve; FAMCAT, Familial Hypercholesterolaemia Case Ascertainment Tool; FH, familial hypercholesterolaemia; NICE, National Institute for Health and Care Excellence; NPV, negative predictive value; PPV, positive predictive value; TC, total cholesterol.