The Program on the Surgical Control of the Hyperlipidemias (posch) and the Lipid Regulatory Hypothesis

Background: The Lipid Regulatory Hypothesis (LRH) states that the best way to regress atherosclerotic plaque is to simultaneously decrease the cholesterol being transported into the arterial wall by low-density lipoprotein (LDL) and increase the cholesterol being removed from the arterial wall, via reverse cholesterol transport, by high-density lipoprotein (HDL). The cholesterol retention fraction (CRF) is defined as (LDL cholesterol minus HDL cholesterol) divided by LDL cholesterol. The Program on the Surgical Control of the Hyperlipidemias (POSCH), which employed partial ileal bypass as the intervention modality, was selected for verification of the LRH and the validity of the CRF. Methods: POSCH coronary arteriographic plaque progression or non-progression (stabilisation/regression) from baseline to 3 years was stratified on a five-by-five factorial grid with 25 cohort cells combining LDL cholesterol and HDL cholesterol changes from baseline to 1 year following intervention. Predictive capacity for arteriography changes of LDL cholesterol and CRF were compared. Statistics used were logistic regressions. Results: There were 731 paired arteriographic assessments of individual POSCH patients: 163 progression (22%) and 568 non-progression (stabilisation/regression) (78%). A reciprocal LDL cholesterol and HDL cholesterol relationship represented as a five-by-five factorial showed non-progression above and progression below the dividing diagonal. 100% (163/163) of patients with plaque progression had a rise in their CRF; and 100% (568/568) of patients with plaque non-progression had a fall in their CRF. LDL cholesterol, HDL cholesterol, and CRF were all highly significant predictors of plaque progression and non-progression (p<0.0001). Conclusion: In POSCH, the partial ileal bypass-induced changes in the LDL cholesterol, HDL cholesterol, and the CRF are highly correlated with the sequential coronary arteriography changes of plaque progression and non-progression. This study affirms that individual patient prognosis can be predicted by the magnitude of response to lipid intervention.