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Una meta-analisi conferma che le HDL sono strettamente associate al rischio cardiovascolare anche in coloro che raggiungono bassi valori di colesterolo LDL

E' un dato ben noto e universalmente accettato che bassi livelli di colesterolo HDL siano associati ad un aumento della probabilità di eventi cardiovascolari, indipendentemente da altri fattori di rischio. Alcuni studi, per esempio il TNT, hanno dimostrato che la concentrazione del colesterolo HDL conserva il suo potere predittivo anche quando il colesterolo LDL viene portato a livelli ottimali e cioè inferiori a 70 mg/dL. In altri studi la relazione non è risultata così chiara e altri ancora, come lo JUPITER, la negano totalmente. La meta-analisi di Boekholdt e coll. conferma il ruolo predittivo del colesterolo HDL nei pazienti in trattamento con statine anche quando si raggiungono valori di colesterolo LDL inferiori a 50 mg/dL. L'aumento dell'apo A-I in corso di terapia con statine, è risultato associato ad una diminuzione del rischio cardiovascolare, suggerendo così la potenzialità protettiva di farmaci in grado di aumentare le HDL.

Levels and changes of HDL cholesterol and apolipoprotein A-I in relation to risk of cardiovascular events among statin-treated patients: a meta-analysis

Boekholdt SM, Arsenault BJ, Hovingh GK, Mora S, Pedersen TR, Larosa JC, Welch KM, Amarenco P, Demicco DA, Tonkin AM, Sullivan DR, Kirby A, Colhoun HM, Hitman GA, Betteridge DJ, Durrington PN, Clearfield MB, Downs JR, Gotto AM Jr, Ridker PM, Kastelein JJ

Circulation 2013;128:1504-1512

BACKGROUND: It is unclear whether levels of high-density lipoprotein cholesterol (HDL-C) or apolipoprotein A-I (apoA-I) remain inversely associated with cardiovascular risk among patients who achieve very low levels of low-density lipoprotein cholesterol on statin therapy. It is also unknown whether a rise in HDL-C or apoA-I after initiation of statin therapy is associated with a reduced cardiovascular risk.
METHODS AND RESULTS: We performed a meta-analysis of 8 statin trials in which lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up. Individual patient data were obtained for 38,153 trial participants allocated to statin therapy, of whom 5387 suffered a major cardiovascular event. HDL-C levels were associated with a reduced risk of major cardiovascular events (adjusted hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.81-0.86 per 1 standard deviation increment), as were apoA-I levels (HR, 0.79; 95% CI, 0.72-0.82). This association was also observed among patients achieving on-statin low-density lipoprotein cholesterol levels <50 mg/dL. An increase of HDL-C was not associated with reduced cardiovascular risk (HR, 0.98; 95% CI, 0.94-1.01 per 1 standard deviation increment), whereas a rise in apoA-I was (HR, 0.93; 95% CI, 0.90-0.97).
CONCLUSIONS: Among patients treated with statin therapy, HDL-C and apoA-I levels were strongly associated with a reduced cardiovascular risk, even among those achieving very low low-density lipoprotein cholesterol. An apoA-I increase was associated with a reduced risk of major cardiovascular events, whereas for HDL-C this was not the case. These findings suggest that therapies that increase apoA-I concentration require further exploration with regard to cardiovascular risk reduction.

Circulation 2013;128:1504-1512