Diabetes, higher Charlson comorbidity index, and heart failure are the most important long-term risk factors of major adverse cardiac event (MACE) in patients after the first acute coronary syndrome (ACS), according to results of a study published in Annals of Medicine.

“The purpose of our study was to evaluate risk factors for MACE within 1- and 3-year time periods after the first ACS event,” the researchers noted. “In particular we wanted to identify modifiable risk factors, which could provide treatment targets for further improvements in prognosis after the first ACS.”

The investigators identified 12,686 patients who survived 28 days after a first ACS and followed them for 3 years using the FINAMI, a database registry of Finns who have had a myocardial infarction. Additionally, the Finnish FINRISK survey also was used to determine the prevalence of risk factors (ie, smoking, hyperlipidemia, diabetes, and hypertension) in post-ACS patients (n=199).

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In patients with a first ACS, 34.4% had MACE within 1 year and 48.4% within 3 years, 17.6% of which were fatal, the researchers reported. Diabetes, heart failure during the first ACS attack hospitalization, higher Charlson comorbidity index, and older age were associated with an increased risk for MACE at 3-year follow-up and revascularization was associated with a decreased risk (Table), the investigators reported.

Table. Risk factors for MACE After a First ACS Eventa 

 MACE at 1 year (n = 4364)
OR (CI / P value)
MACE at 3 years (n = 6094)
OR (CI / P Value)
Age (per 10 years)0.94 (0.88-1.01; P =0.08)1.07 (1.01–1.14; P =0.026)
Sex (female)0.88 (0.77-1.02; P =0.095)0.93 (0.81–1.06 P =0.28)
Event year0.99 (0.97-1.00; P =0.13)0.98 (0.97–1.00; P =0.077)
Diabetes1.39 (1.17-1.64; P =1.3 × 10−4)1.51 (1.29–1.77; P =4.4 × 10−7)
Cholesterol (per SD)1.00 (0.92-1.07; P =0.93)0.96 (0.9–1.03; P =0.28)
Current smoking1.12 (0.96-1.31; P =0.14)1.14 (0.98–1.31; P =0.081)
Revascularization (within 28 days)0.84 (0.73-0.97; P =0.021)0.82 (0.71–0.94; P =0.0036)
Primary HF1.95 (1.63-2.34; P =1.9 × 10−13)1.98 (1.67–2.36; P =6.8 × 10−15)
Primary AF1.1 (0.91-1.33; P =0.33)1.11 (0.93-1.33; P =0.25)
Use of thrombolytic treatment1.12 (0.94-1.32; P =0.2)1.18 (1.01-1.38; P =0.035)
Charlson comorbidity index* per 1 point1.11 (1.09-1.13; P =1.94 × 10−21)1.09 (1.07-1.12; P =1.56 × 10−19)
UAP (as AHADG, 15.4% of all cases)0.99 (0.83-1.17; P =0.89)1.11 (0.95-1.3; P =0.18)
MACE, major adverse cardiac event; ACS, acute coronary event; OR, odds ratio; SD, standard deviation; HF, heart failure; AF, atrial fibrillation.
aAll risk factors were modeled independently of other risk factors and adjusted for age, sex, and event year. 
bCalculated in a separate model, because the Charlson comorbidity index includes primary HF and AF, adjusted for age and sex. The other ORs were produced in the same model.
Reprinted from Okkonen et al.

Smoking at the time of first ACS was associated with an elevated risk of future MACE but did not reach statistical significance because many of the patients stopped smoking after their first event. Approximately one-fourth of patients (23%) survivors continued smoking after a first ACE and 24% had high cholesterol levels (>5 mmol/L). 

“Major improvements have taken place in the diagnosis and treatment of ACS during our study period,” the researchers stated. “To explore the effects of improved treatments, we carried out a separate analysis for the later study years, 2006–2011.”

Improvements were shown in both short- and long-term survival; however, the portion of recurrent MACE events remained the same among survivors.

“Because of the amount of revascularization procedures has reached a plateau, it is fair to assume that if we aim to improve long-term prognosis of ACS patients we should also target the modifiable risk factors,” the researchers noted.

The study showed that in the elderly and patients with diabetes, “suboptimal use of medication, and thus suboptimal secondary prevention, could in part explain the high MACE rates for these patients,” noted the investigators. Information about medication use was not available in the study.

Diabetes mellitus and heart failure are the most important risk factors for MACE and ACS, concluded the authors. Based on their findings, “hypercholesterolemia should be treated aggressively and patients should be encouraged to stop smoking,” they concluded. 


Okkonen M, Havulinna A, Ukkola O, Huikuri H, Pietila A, Koukkunen H. https://www.tandfonline.com/doi/epub/10.1080/07853890.2021.1924395?needAccess=true. Ann Med. 2021;53:(1): 817-823. doi:10.1080/07853890.2021.1924395