Lower non–HDL-c levels associated with better outcomes after MI

In a large, Swedish observational study among patients with a first MI, the lowest risk of MACE was observed when the non–HDL-c target (<2.2 mmol/L) was achieved within 2 months of the MI and sustained during the first year.

This summary is based on the publication of Schubert J, Leosdottir M, Lindahl B, et al. - Intensive early and sustained lowering of non–high-density lipoprotein cholesterol after myocardial infarction and prognosis: the SWEDEHEART registry. Eur Heart J. 2024 Sep 1:ehae576 [Online ahead of print]. doi: 10.1093/eurheartj/ehae576

Introduction and methods

Background

To achieve lipid goals, European clinical guidelines recommend a stepwise approach, comprising statins and addition of non-statin lipid-lowering therapies if needed [1,2]. However, in patients with an MI, this tactic could lead to delays in the achievement of lipid targets and reduction of adverse events [3-5]. Although LDL-c levels are the principal target for lipid-modifying treatment, equivalent non–HDL-c and apoB concentrations have been included as secondary targets in most evidence-based guidelines. In contrast to apoB, non–HDL-c levels are routinely available, by subtracting HDL-c from total cholesterol levels.

Aim of the study

The study aim was to assess the relationship between non–HDL-c levels (and change therein) and risk of adverse outcomes in post-MI patients.

Methods

For this observational study, data were collected from nationwide SWEDEHEART (Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies) registry for 56,262 patients who were hospitalized for a first MI in Sweden in the period January 2005 through January 2022 and subsequently participated in a cardiac rehabilitation program (86% of patients had not received statin treatment prior to hospitalization). Non–HDL-c levels were measured at hospital admission and 1 year. Median follow-up duration was 5.4 years (IQR: 2.6–8.9).

Outcomes

The endpoints were (1) MACE, a composite outcome of all-cause mortality, nonfatal MI, or nonfatal ischemic stroke; (2) all-cause mortality; and (3) nonfatal MI.

Main results

Long-term outcomes

• The incidence rate of MACE from 1 year to the maximum follow-up time point of 12 years decreased across quartiles of non–HDL-c reduction from baseline to 1 year.
• Compared with patients with the smallest non–HDL-c reduction (<0.7 mmol/L), patients with a non–HDL-c reduction 0.7–1.4 mmol/L had a 16% lower risk of MACE after 1 year (adjusted HR (aHR): 0.84; 95%CI: 0.79–0.89), those with a non–HDL-c reduction 1.5–2.1 mmol/L had a 29% lower MACE risk (aHR: 0.71; 95%CI: 0.66–0.76), and those with the greatest non–HDL-c reduction (≥2.2 mmol/L) had a 37% lower MACE risk (aHR: 0.63; 95%CI: 0.57–0.67; P for trend<0.001).
• Similar trends were seen for the incidence rates of all-cause mortality (up to 21% risk reduction; P for trend<0.001) and nonfatal MI (up to 49% risk reduction; P for trend<0.001).
• Across quartiles of achieved non–HDL-c levels at 1 year, patients in the lowest quartile (≤1.9 mmol/L) had the lowest risks of MACE after 1 year (aHR: 0.76; 95%CI: 0.71–0.81; P for trend<0.001) and nonfatal MI after 1 year (aHR: 0.69; 95%CI: 0.62–0.77; P for trend<0.001) compared with those in the highest quartile (>2.9 mmol/L). Of note, participants with achieved non–HDL-c levels below the median (2.3 mmol/L) showed comparable risk reductions.
• For the endpoint of all-cause mortality, the lowest long-term risk was seen in patients with achieved non–HDL-c 2.0–2.2 mmol/L (aHR: 0.82; 95%CI: 0.76–0.89).
• Spline analysis of the continuous relationship between achieved non–HDL-c levels at 1 year and outcomes (HR set to 1.00 at median non–HDL-c level of 2.3 mmol/L) demonstrated the risks of all 3 endpoints were linearly associated with the achieved non–HDL-c levels at 1 year, with the lowest HR being observed for patients achieving a non–HDL-c level of just below 2.0 mmol/L.

Early and sustained non–HDL-c target achievement

• In a subset analysis of patients with non–HDL-c measurements at baseline, 2 months, and 1 year (n=46,518; 83% of total population), the 1-year MACE risk was lowest in patients achieving the non–HDL-c target (<2.2 mmol/L) at 2-month follow-up and maintaining it at 1 year compared with patients with non–HDL-c ≥2.2 mmol/L at 2 months and 1 year (aHR: 0.80; 95%CI: 0.74–0.86).
• Patients who only achieved the target early (aHR: 0.86; 95%CI: 0.80–0.93) and those only achieving the target at 1-year follow-up (aHR: 0.86; 95%CI: 0.79–0.93) showed a similar 1-year MACE risk (P for trend<0.001).

Short-term outcomes

• To internally validate the principal findings, a landmark analysis was performed in patients with non–HDL-c measurements at baseline and 2 months (n=60,452). This analysis showed the short-term (2–12 months) MACE risk was also decreased across quartiles of non–HDL-c reduction from baseline to 2 months and across quartiles of achieved non–HDL-c levels at 2 months.
• Patients in the highest quartile of non–HDL-c reduction between baseline and 2 months had a 28% reduction in MACE risk up to 1 year compared with those in the lowest quartile (aHR: 0.72; 95%CI: 0.59–0.87), whereas patients in the lowest quartile of non–HDL-c levels at 2 months had a 20% MACE risk reduction compared with those in the highest quartile (aHR: 0.80; 95%CI: 0.68–0.92).
• Similar results were observed for all-cause mortality and nonfatal MI, except for a nonsignificant association between quartiles of achieved non–HDL-c levels at 2 months and risk of all-cause mortality during the first year (P for trend=0.650).

Conclusion

In this large, Swedish observational study among patients with a first MI, those with the lowest non–HDL-c levels or the largest non–HDL-c reduction at 2 months or 1 year had the lowest risk of MACE and, to a lesser extent, all-cause mortality. The lowest risk was observed when the non–HDL-c target (<2.2 mmol/L) was achieved within 2 months of the MI and sustained during the first year. The authors state that their “analyses of the temporal relationship between change in non–HDL-c and outcomes suggest that early achievement of target non–HDL-c levels after MI, and its subsequent maintenance, was linked to better prognosis vs. achieving target levels at a later stage.”

Find this article online at Eur Heart J.

References

1. Visseren FLJ, Mach F, Smulders YM, Carballo D, Koskinas KC, Bäck M, et al. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J 2021;42: 3227–337. doi: https://doi.org/10.1093/eurheartj/ehab484
2. Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, et al. ESC Scientific Document Group. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2020;41:111–88. doi: https://doi.org/10.1093/eurheartj/ehz455
3. Schubert J, Lindahl B, Melhus H, Renlund H, Leosdottir M, Yari A, et al. Low-density lipoprotein cholesterol reduction and statin intensity in myocardial infarction patients and major adverse outcomes: a Swedish nationwide cohort study. Eur Heart J 2021;42: 243–52. doi: https://doi.org/10.1093/eurheartj/ehaa1011
4. Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med 2015;372: 2387–97. doi: https://doi.org/10.1056/nejmoa1410489
5. Hagström E, Steg PG, Szarek M, Bhatt DL, Bittner VA, Danchin N, et al. Apolipoprotein B, residual cardiovascular risk after acute coronary syndrome, and effects of alirocumab. Circulation 2022;146:657–72. doi: https://doi.org/10.1161/circulationaha.121.057807