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Progression of coronary atherosclerosis in patients with probable familial hypercholesterolemia. Quantitative arteriographic assessment of patients in NHLBI type II study.
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1989
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HypertensionVascular DiseaseHeart FailureGenetic EpidemiologyHyperlipidemiaCoronary Artery DiseaseProbable Familial HypercholesterolemiaPercent StenosisBiostatisticsPublic HealthCardiologyAtherosclerosisDyslipidemiaCardiovascular EpidemiologyStenosis ResistanceMedicineQuantitative Arteriographic AssessmentEpidemiologyCardiovascular Disease Risk AssessmentCoronary Heart DiseaseCoronary AtherosclerosisCardiovascular DiseaseArterial DiseaseStrokeCardiovascular Genetics
A computer-assisted method for quantitatively assessing progression and regression of coronary atherosclerosis has been applied, in a fully blinded fashion, to a set of 116 5-year-interval coronary arteriograms obtained between 1972 and 1981 in the National Heart, Lung, and Blood Institute (NHLBI) Type II Study. Coronary changes are described in 54 of these patients who had tendinous xanthomata and hypercholesterolemia consistent with the diagnosis of familial hypercholesterolemia. Among 468 patent lesions of all degrees of severity and among 25 total occlusions identified on the initial arteriogram, 11% progressed by the 95% confidence criterion for assessing change in percent stenosis (+/- 17%), and 1% regressed by using the same criterion. Among 54 patients, 50% had progression only, 6% had regression only, and 4% had mixed progression and regression. Because half of these patients were treated with cholestyramine, these frequencies may underestimate the natural history of their disease progression. Comparable frequencies were obtained by using the 95% confidence criterion for change in stenosis resistance (Rp ratio outside range, 0.35 to 2.9). In properly obtained arteriograms, the Rp parameter is physiologically relevant and is a sensitive index of lesion change with a high signal-to-noise ratio; we advocate its use for detection of progression and regression. Morphologic features, including luminal irregularity and ulceration, increased the likelihood of progression by 1.8- to 5-fold. Surprisingly, significant arterial flexing at the site of the lesion predicted anatomic stability. A lumen narrowed by visible thrombus was 100-fold more likely to regress than were those without it. The initial severity of stenosis correlated strongly with new total occulusion and with disease progression as assessed by Rp change. Because lesion-specific features are important determinants of lesion change, intervention trials that statistically account for the contributions of lesion morphology are likely to provide a more insightful assessment of the therapeutic benefit.