Intensive early and sustained lowering of non-high-density lipoprotein cholesterol after myocardial infarction and prognosis: the SWEDEHEART registry

Abstract

Background and aims: Non-HDL-C provides an estimate of lipid-associated risk and is a secondary treatment target after myocardial infarction (MI). The aim was to study the relationship between non-HDL-C levels after MI and risk of adverse outcomes.

Methods: From the SWEDEHEART registry, 56 262 patients with MI were included. Outcomes were major adverse cardiovascular event (MACE: death, MI, and ischaemic stroke), death, and non-fatal MI. Non-HDL-C was assessed at admission, 2 months, and 1 year. Target achievement (<2.2 mmol/L) of non-HDL-C, timing thereof, and outcomes were assessed.

Results: During median follow-up of 5.4 years, 9549 had MACE, 5427 died, and 3946 had MI. Long-term hazard ratio (HR) for MACE in the lowest vs. the highest quartile of achieved non-HDL-C at 1 year was 0.76 [95% confidence interval (CI) 0.71-0.81]. Short-term results were consistent also when assessing non-HDL-C levels at 2 months, including early events up to 1 year (HR 0.80, 95% CI 0.68-0.92). Similar results were observed for all outcomes. Patients achieving both early and sustained targets had lowest risk of outcomes (HR 0.80, 95% CI 0.74-0.86) vs. patients achieving target early or late (HR for both 0.86, 95% CI 0.79-0.93).

Conclusions: The lowest achieved levels both at 2 months and at 1 year of non-HDL-C were associated with better outcome. The lowest risk was observed when target was achieved within 2 months of MI and sustained thereafter. These findings challenge the current stepwise approach for cholesterol lowering after MI, which inevitably results in delaying goal attainment and possible harm.

Keywords: Death; MACE; Myocardial infarction; Non–HDL-cholesterol; Secondary prevention.

Structured Graphical Abstract

Non−HDL-C values at MI admission and early and late follow-up (left panel). Adjusted cox proportional hazard models for MACE for early, late, and early and sustained achievement of <2.2 mmol/L (right panel). Major adverse cardiovascular events are the composite outcome of all-cause mortality, myocardial infarction, or ischaemic stroke. CI, confidence interval; HR, hazard ratio; non−HDL-C, non−high-density lipoprotein cholesterol.

Figure 1

Cumulative incidence rates by outcome and change in non–HDL-C at 1 year after myocardial infarction. Kaplan–Meier curves of the cumulative incidence rates by quartile non–HDL-C reduction from index myocardial infarction to the follow-up visit. Log-rank test < .001 for all outcomes. Major adverse cardiovascular event is the composite outcome of all-cause mortality, myocardial infarction, or ischaemic stroke. MACE, major adverse cardiovascular event; non–HDL-C, non–high-density lipoprotein cholesterol

Figure 2

Event rates and hazard ratios by quartiles (A and C) of achieved non–HDL-C and (B and D) change in non–HDL-C between index myocardial infarction and 2-month follow-up (upper panels) and 1-year follow-up (lower panels). The upper panels shows events between 2-month follow-up and 1 year and the lower panels from 1 year to a maximum of 12 years. Event rate per 100 person-years. Models were adjusted for age at follow-up, statin intensity at admission, systolic blood pressure at follow-up, smoking at follow-up, sex, statin intensity at follow-up, body mass index at follow-up, history of diabetes, creatinine at admission, non–HDL-C at admission, and left ventricular ejection fraction at admission. Major adverse cardiovascular event is the composite outcome of all-cause mortality, myocardial infarction, or ischaemic stroke. CI, confidence interval; MACE, major adverse cardiovascular event; non–HDL-C, non–high-density lipoprotein cholesterol

Figure 3

(A) Event rates and hazard ratios for quartiles of achieved non–HDL-C between index myocardial infarction and 1-year follow-up and (B) association between achieved values of non–HDL-C and outcomes. Event rate per 100 person-years. Models were adjusted for age at follow-up, statin intensity at admission, systolic blood pressure at 1-year follow-up, smoking at 1-year follow-up, sex, statin intensity at 1-year follow-up, body mass index at 1-year follow-up, history of diabetes, creatinine at admission, non–HDL-C at admission, and left ventricular ejection fraction at admission. MACE is the composite outcome of all-cause mortality, myocardial infarction, or ischaemic stroke. MACE, major adverse cardiovascular event; MI, myocardial infarction; non–HDL-C, non–high-density lipoprotein cholesterol

Figure 4

(A) Non–HDL-C values at myocardial infarction admission and early and late goal achievement. (B) Adjusted Cox proportional hazards models and event rates per 100 person-years are presented, adjusted for age at 1-year follow-up, statin intensity at admission, systolic blood pressure at 1-year follow-up, smoking at 1-year follow-up, sex, statin intensity at 1-year follow-up, body mass index at 1-year follow-up, history of diabetes, creatinine at admission, non–HDL-C at admission, and left ventricular ejection fraction at admission. MACE is the composite outcome of all-cause mortality, myocardial infarction, or ischaemic stroke. MACE, major adverse cardiovascular event; MI, myocardial infarction; non–HDL-C, non–high-density lipoprotein cholesterol; IQR, interquartile range; CI, confidence interval