Diabetes and cardiovascular prevention: bridging two epidemics

This issue of EJPC focuses on cardiovascular risk and cardioprotective treatments in the context of Type 2 diabetes (T2D). Making a meta-analysis of 82 studies (9440 patients) in New diagnosis of diabetes in patients with myocardial infarction or stroke: a systematic review and meta-analysis, Douelrachad et al.1 from Canada reported that one out of six patients hospitalized for myocardial infarction is newly diagnosed for diabetes, a proportion remaining stable over the last 30 years. This underscores the urgent need to improve population screening for diabetes. Beyond medical consequences, in The reduction of the productivity burden of cardiovascular disease by improving the risk factor control among Australians with type 2 diabetes: a 10-year dynamic analysis, Abushanab et al.2 from Australia explored the societal and economic effects of some intervention scenarios, including a 19% reduction of tobacco use, 17% decrease of systolic blood pressure (SBP), 58% lower incidence of diabetes, and a 39 mg/dL total cholesterol reduction. These ambitious targets yielded substantial gain in productivity and economic outcomes, highlighting the strong interconnection between individual health and population-level productivity. Evaluating cardiovascular risk in T2D patients remains a major challenge. Numerous risk-prediction models have been developed, but their real-life performance remains heterogenous. In External validation of cardiovascular risk scores in patients with type 2 diabetes using the Spanish population-based CARDIANA cohort, Enguita-Germán et al.3 from Spain compared the accuracy of 13 models in the T2D patient population and 5 models in the general population for cardiovascular risk prediction over a 5-year follow-up period in their cohort. The models specifically developed for T2D, particularly SCORE2-diabetes and ADVANCE, emerged as the top-performing tools. While the SCORE2-OP model was developed to estimate cardiovascular risk, it is not applicable to elderly individuals with T2D. In Development and validation of the CARE-DM model to predict the cardiovascular risk in older persons with type 2 diabetes, Aponte Ribero et al.4 from Spain addressed this limitation, using data from 12 countries (>6900 patients with T2D aged ≥65 years). The CARE-DM model enabled to predict accurately 5–10-year cardiovascular risk, based on clinical characteristics and diabetes treatment.4 Similarly, Bai et al.5 from China demonstrated the usefulness of composite clinical and biological indices to predict heart failure in elderly patients in Advanced prediction of heart failure risk in elderly diabetic and hypertensive patients using nine machine learning models and novel composite indices: insights from NHANES 2003–2016. In Circadian heart rate fluctuations predict cardiovascular and all-cause mortality in Type 2 and Type 1 diabetes: a 21-year retrospective longitudinal study, Nesti et al.6 from Italy highlight the strong association between heart rate (HR) variability and micro- and macrovascular complications in both type-1 and T2D over an impressive follow-up of 21 years. Low 24 h and nocturnal HR fluctuations, measured by ambulatory blood pressure and HR monitoring, were associated with microvascular complications and death (Figure 1). Notably, reduced 24 h HR fluctuations were associated with a twofold increase in CV mortality and a 61% increase in all-cause mortality, even after adjustment for confounders.6 Kaplan–Meier curves and 95% confidence intervals for subjects stratified by 24 h heart rate standard deviation (24 h HR SD) (A and B) and nocturnal HR dip (C and D). Among anti-diabetic drugs, sodium–glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonist (GLP-1RA) have shown their efficacy to reduce cardiovascular events. Musella et al.7 from Sweden explored treatment choice in Pharmacological treatment patterns and outcomes according to the coexistence of heart failure and type 2 diabetes: data from the Swedish Heart Failure Registry and National Diabetes Registry. They examined the bidirectional influence of heart failure and T2D regarding treatment choice, including 37 903 patients with heart failure and 16 266 patients with T2D. Patients with heart failure and concomitant T2D had a 10-fold higher use of SGLT2i compared to those without T2D. However, the same patients were less likely to use mineraloid receptor antagonists (MRA) and renin–angiotensin system inhibitors (RASi), even after adjustment for renal function and potassium levels. Conversely, among patients with T2D, heart failure was independently associated with higher SGLT2i use and lower metformin use. The widespread use of SGLT2i suggests that this drug is both clinically trusted and well-accepted by prescribers.7 Regarding GLP1-RA therapy, Krychtiuk et al.8 from the USA provided further reassuring evidence in Albiglutide and atrial fibrillation in patients with type 2 diabetes and established cardiovascular disease: insights from the Harmony Outcomes trial. Early in the albiglutide development programme, concerns were raised about the risk of atrial fibrillation/atrial flutter (AF) with this drug. Over a 1.6-year follow-up, this post hoc analysis demonstrated that albiglutide, compared with placebo, reduced the risk of major adverse cardiovascular events irrespective of AF history [history of AF: adjusted hazard ratio (aHR) 0.83 (0.58–1.19), no history of AF aHR 0.77 (0.66–0.90); Pinteraction = 0.71]. Albiglutide was not associated with an increased risk of AF during follow-up (Figure 2). Forrest plot of treatment effect for each event type. AFB, atrial fibrillation, AFLU, atrial flutter. Current clinical guidelines recommend a combination of three therapies to delay CKD progression: RASi, SGLT2i, and MRA. In Expert perspectives on incorporating glucagon-like peptide-1 receptor agonist in diabetes and chronic kidney disease: challenges and opportunities, Halimi et al.9 from France summarized the efficacy and safety profiles of each treatment class, including GLP1-RA as the newcomer, and discussed the rationale for sequential or combination therapy according to an individualized approach. To refine this individualized approach, Mori et al.10 from Japan conducted the Heterogeneous cardiovascular effects of sodium-glucose cotransporter 2 inhibitors in type 2 diabetes: a causal forest and target trial emulation study, using a nationwide cohort of working-age Japanese with T2D. Over a 3-year follow-up, the benefit of SGLT2i was weakly correlated with CV risk estimation (r = 0.29) but better correlated with some individual characteristics, including SBP (r = 0.74), BMI (r = 0.33), and fasting plasma glucose (r = 0.35). Similarly, in Effect of sodium-glucose cotransporter-2 inhibitors on kidney outcomes of individuals with type 2 diabetes according to blood pressure levels, Jimba et al. from Japan found that the protective effect of SGLT2i on renal function was more pronounced among T2D patients with higher SBP, particularly in those with preserved renal function without antihypertensive drugs.11 In The association of haptoglobin levels and phenotype with cardiovascular disease in type 2 diabetes: a Fenofibrate Intervention and Event Lowering in Diabetes sub-study, Ong et al.12 from Australia reported that higher haptoglobin levels were associated with an increased risk of cardiovascular events, but the benefits of fenofibrate did not differ by haptoglobin phenotypes, baseline levels, or in-trial changes. Along with editorials, rapid communications, and letters, this issue highlights the need for a better understanding of the complexity of cardiometabolic health and the need for a close collaboration between the cardiovascular and diabetes specialists around our patients. Victor Aboyans (Writing—review & editing [supporting]) and Laurence Salle (Writing—original draft [lead]) No new data were generated or analysed in support of this research.

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