What is the first major CV event in T2D?

12th February 2026, A/Prof Chee L Khoo

First CV event?

When we think about major complications in patients with type 2 diabetes (T2D), we automatically think of an atherosclerotic cardiovascular event. While diabetic kidney disease, diabetic foot disease and retinopathy makes the quality of life miserable the last 5-7 years of their shortened lifespan but it is ASCVD events that kills them. Another common cardiovascular complication is heart failure (HF). HF has been reported to be one of the most common first presentations of CVD among people with type 2 diabetes (1-3).

If we can identify those risk factors specific to HF occurring as the first-ever presentation of CVD, this would enable more comprehensive risk stratification in primary prevention, inclusive of all the possible first presentations of CVD in type 2 diabetes. Indeed, this is becoming increasingly important as advocacy for HF screening in type 2 diabetes grows and clinicians face decisions between prescribing SGLT2 inhibitors versus GLP-1 receptor agonists—each with their own distinct CVD benefits (4-6).        

One of the problems of trying to work out the prevalence of HF in patients with T2D is that clinical trials group ASCVD events, cardiac deaths and HF as CVD. We really don’t know the breakdown of these events and their associated risk factors. A recent study explored the risk factors associated with ASCVD and HF as the first presentation of CVD among patients with T2D. Sacre J et al used data from two very well validated studies, REWIND and ORIGIN trials to answer those queries (7).

In the REWIND study, dulaglutide was shown to reduce the risk of multiple CV outcomes (8). So, Sacre et all used data from the placebo arm. They also excluded patients who were on other GLP1-RA, SGLT2 inhibitors. In the ORIGIN trial, insulin glargine did not improve CV outcomes (9). Thus, all the participants in the ORIGIN trial were included in the post hoc analysis.

They restrict their analyses to those without prior CVD. People with a history of MI, stroke, revascularisation, angina, myocardial ischemia, or HF were excluded. Participants with subclinical CVD or CV risk factors  (≥50% arterial stenosis, left ventricular hypertrophy, ankle-brachial index < 0.9 or albuminuria. In the REWIND trial, participants with eGFR 1.0 (men) or >0.8 (women) or at least two of the following if aged 60+ years: smoking, dyslipidaemia, hypertension, or waist-hip ratio >1.0 (men) or >0.8 (women) were also included. Participants were followed until their first major CV event, non-CV death, or the end of trial follow-up.

The results

Overall, the mean age was 64 years, and 50.1%were female. Glycaemia was mostly well controlled (meanHbA1c7.0%), 32%showedevidenceof at least moderately increased albuminuria and 21%reducedeGFR. Of the 6175participants,1024(16.6%) had an incident CV event during a median of 5.8years follow-up.

In the total study population, the majority of first events were ASCVD (65.2%; comprising similar proportions of ACS, stroke, and revascularization), followed by other CV death (18.0%) and HF (16.8%).

In general, as expected, the incidence of events increased with increasing age but the distribution of the events shifted with increasing age. At age 55 years, both HF and other CV death were infrequent as first events, occurring at 0.15 and 0.12 times the rate of CVD mani fest as ASCVD, respectively. By 85 years of age, HF event occurred at 0.52 times the rate of CVD manifest as ASCVD, while other CV death was almost as frequent as ASCVD (rate ratio = 0.88).

We know the multiple risk factors associated with CVD – male gender, smoking, high BMI, hypertension, dyslipidaemia, hyperglycaemia, diabetes duration, chronic kidney disease, ethnicity and whether the patient is on statins or not. Whereas most risk factors showed similar relationships with all three event types, higher LDL-cholesterol, higher HbA1c, and higher systolic BP only predicted CVD manifest as an ASCVD event; higher BMI only predicted CVD manifest as a HF event; and non White status and non-use of statins only predicted other CV death.

At age 65 years in patients with ASCVD -specific risk factors, an ASCVD event was estimated to occur first in 83.8% of cases of CVD with HF events (7.9%) and other CV deaths (8.2%) first among the remaining cases. In patients with HF-specific risk factors, the distribution of CVD was expected to be 60.5% ASCVD events, 26.8% HF events, and 12.6% other CV death.

Ageing progressively shifted the distribution so that ASCVD events became proportionately less frequent, and HF events and other CV death proportionately more frequent, with older age. Indeed, ASCVD was estimated to be the first event in less than half of all cases of CVD (43.5%) at age 75 years in the presence of worse HF-specific risk factors, due to higher rates of HF (32.0% of first events) and other CV death (24.5%).

HF sometimes precede ASCVD event in patients with T2D. In this study, the overall HF event is the first major CV event in 16.8%. However, in patients with HF-specific risk factors (obesity and CKD), the distribution was up to 26.8%. In older patients, HF can be as high as 32% of first events.

Importantly, randomised controlled trials have shown improved outcomes from HF screening, linked to initiation/up-titration of well-established cardioprotective therapies.28 Moreover, we now have access to SGLT2 inhibitors, which have well-established efficacy for HF prevention, including among people without prior CVD (29).

Many of these patients are managed in primary care. AHA/ACC/Heart Failure Society of America HF guidelines now advocate HF risk stratification in primary prevention and screening for subclinical HF is recommended in people with type 2 diabetes via annual measurement of natriuretic peptides (NT-proBNP or proBNP) (10,11).

References

  1. Shah AD, Langenberg C, Rapsomaniki E, et al. Type 2 diabetes and incidence of cardiovascular diseases: a cohort study in 1.9 million people. Lancet Diabetes Endocrinol. 2015;3:105-113.
  2. Blin P, Joubert M, Jourdain P, et al. Cardiovascular and renal diseases in type 2 diabetes patients: 5-year cumulative incidence of the first occurred manifestation and hospitalization cost: a cohort within the French SNDS nationwide claims database. Cardiovasc Diabetol. 2024;23:22.
  3. Sacre JW, Magliano DJ, Shaw JE. Incidence of hospitalization for heart failure relative to major atherosclerotic events in type 2 diabetes: a meta-analysis of cardiovascular outcomes trials. Diabetes Care. 2020;43:2614-2623.
  4. Pop-Busui R, Januzzi JL, Bruemmer D, et al. Heart failure: an underap preciated complication of diabetes. A consensus report of the Ameri can Diabetes Association. Diabetes Care. 2022;45:1670-1690.
  5. American Diabetes Association Professional Practice Committee. Pharmacologic approaches to glycemic treatment: standards of care in diabetes-2025. Diabetes Care. 2025;48:S181-S206.
  6. Sacre JW, Magliano DJ, Shaw JE. Clinical utility of cardiovascular risk scores for identification of people with type 2 diabetes more likely to benefit from either GLP-1 receptor agonist or SGLT2 inhibitor ther apy. Diabetes Care. 2022;45:1900-1906.
  7. Sacre JW, Lundegard K, Mohammedi K, Carstensen B, Gerstein HC, Shaw JE. Prediction of heart failure as the first major cardiovascular disease event in type 2 diabetes. Diabetes Obes Metab. 2026;
  8. Gerstein HC, Colhoun HM, Dagenais GR, et al. Design and baseline characteristics of participants in the researching cardiovascular events with a weekly INcretin in diabetes (REWIND) trial on the cardiovascular effects of dulaglutide. Diabetes Obes Metab. 2018;20:42-49.
  9. Origin Trial Investigators, Gerstein H, Yusuf S, Riddle MC, Ryden L, Bosch J. Rationale, design, and baseline characteristics for a large international trial of cardiovascular disease prevention in people with dysglycemia: the ORIGIN trial (outcome reduction with an initial glar gine intervention). Am Heart J. 2008;155:26-32.e1-6.
  10. Pop-Busui R, Januzzi JL, Bruemmer D, et al. Heart failure: an underap preciated complication of diabetes. A consensus report of the Ameri can Diabetes Association. Diabetes Care. 2022;45:1670-1690.
  11. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the Ameri can College of Cardiology/American Heart Association Joint Commit tee on clinical practice guidelines. Circulation. 2022;145:e895-e1032.