Journal of Clinical Medicine Article Prognosis Impact of Diabetes in Elderly Women and Men with Non-ST Elevation Acute Coronary Syndrome Pablo Díez-Villanueva 1 , Jose María García-Acuña 2 , Sergio Raposeiras-Roubin 3 , Jose A. Barrabés 4 , Alberto Cordero 5 , Manuel Martínez-Sellés 6 , Alfredo Bardají 7 , Francisco Marín 8 , Juan M. Ruiz-Nodar 9 , Nuria Vicente-Ibarra 10 , Gonzalo L. Alonso Salinas 11 , Belén Cid-Alvárez 2 , Emad Abu Assi 3 , Frances Formiga 12 , Julio Núñez 13 , Eduardo Núñez 13 , Albert Ariza-Solé 14 and Juan Sanchis 13, * 1 Servicio de Cardiología, Hospital Universitario La Princesa, 28006 Madrid, Spain; pablo_diez_villanueva@hotmail.com 2 Servicio de Cardiología, Hospital Clínico Universitario de Santiago, CIBERCV, 15706 Santiago de Compostela, A Coruña, Spain; jgarciaacuna@gmail.com (J.M.G.-A.); belenalvarez85@hotmail.com (B.C.-A.) 3 Servicio de Cardiología, Hospital Álvaro Cunqueiro de Vigo, 36213 Vigo, Pontevedra, Spain; Sergio.Raposeiras.Roubin@sergas.es (S.R.-R.); eabuassi@yahoo.es (E.A.A.) 4 Servicio de Cardiología, Hospital Universitario Vall d’Hebron, Universidad Autónoma de Barcelona, CIBERCV, 08035 Barcelona, Spain; jabarrabes@vhebron.net 5 Servicio de Cardiología, Hospital Clínico Universitario de San Juan, 03550 Alicante, Spain; acorderofort@gmail.com 6 Servicio de Cardiología, Hospital Universitario Gregorio Marañón, CIBERCV, Universidad Europea,  Universidad Complutense, 28007 Madrid, Spain; mmselles@secardiologia.es  7 Servicio de Cardiología, Hospital Universitario de Tarragona Joan XXIII, IISPV, Universitat Rovira i Virgili, Citation: Díez-Villanueva, P.; 43005 Tarragona, Spain; abardaji@comt.es 8 Servicio de Cardiología, Hospital Clínico Universitario Virgen de la Arrixaca, IMIB-Arrixaca, CIBERCV, García-Acuña, J.M.; Raposeiras- Roubin, S.; Barrabés, J.A.; Cordero, A.; 30120 Murcia, Spain; fcomarino@hotmail.com 9 Servicio de Cardiología, Hospital General Universitario de Alicante, 03010 Alicante, Spain; ruiz_jmi@gva.es Martínez-Sellés, M.; Bardají, A.; 10 Cardiology Department, Hospital General de Elche, 03203 Alicante, Spain; nuria.v.ibarra@gmail.com Marín, F.; Ruiz-Nodar, J.M.; Vicente- 11 Servicio de Cardiología, Hospital Universitario Ramón y Cajal de Madrid, CIBERCV, 28034 Madrid, Spain; Ibarra, N.; et al. Prognosis Impact of gonzalol.alonso@gmail.com Diabetes in Elderly Women and Men 12 Servicio de Medicina Interna, Hospital Bellvitge, L’Hospitalet de Llobregat, 08097 Barcelona, Spain; with Non-ST Elevation Acute fformiga@bellvitgehospital.cat Coronary Syndrome. J. Clin. Med. 13 Servicio de Cardiología, Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, 2021, 10, 4403. https://doi.org/ CIBERCV, 46014 Valencia, Spain; yulnunez@gmail.com (J.N.); enunezb@gmail.com (E.N.) 14 Servicio de Cardiología, Hospital Bellvitge, L’Hospitalet de Llobregat, 08097 Barcelona, Spain; 10.3390/jcm10194403 aariza@bellvitgehospital.cat Academic Editor: Simone Biscaglia * Correspondence: sanchis_juafor@gva.es Received: 30 August 2021 Abstract: Few studies have addressed to date the interaction between sex and diabetes mellitus Accepted: 21 September 2021 (DM) in the prognosis of elderly patients with non-ST-segment elevation acute coronary syndrome Published: 26 September 2021 (NSTEACS). Our aim was to address the role of DM in the prognosis of non-selected elderly patients with NSTEACS according to sex. A retrospective analysis from 11 Spanish NSTEACS registries Publisher’s Note: MDPI stays neutral was conducted, including patients aged ≥70 years. The primary end point was one-year all-cause with regard to jurisdictional claims in mortality. A total of 7211 patients were included, 2,770 (38.4%) were women, and 39.9% had DM. published maps and institutional affil- Compared with the men, the women were older (79.95 ± 5.75 vs. 78.45 ± 5.43 years, p < 0.001) and iations. more often had a history of hypertension (77% vs. 83.1%, p < 0.01). Anemia and chronic kidney disease were both more common in women. On the other hand, they less frequently had a prior history of arteriosclerotic cardiovascular disease or comorbidities such as peripheral artery disease and chronic pulmonary disease. Women showed a worse clinical profile on admission, though Copyright: © 2021 by the authors. an invasive approach and in-hospital revascularization were both more often performed in men Licensee MDPI, Basel, Switzerland. (p < 0.001). At a one-year follow-up, 1090 patients (15%) had died, without a difference between This article is an open access article sexes. Male sex was an independent predictor of mortality (HR = 1.15, 95% CI 1.01 to 1.32, p = 0.035), distributed under the terms and and there was a significant interaction between sex and DM (p = 0.002). DM was strongly associated conditions of the Creative Commons Attribution (CC BY) license (https:// with mortality in women (HR: 1.45, 95% CI = 1.18–1.78; p < 0.001), but not in men (HR: 0.98, creativecommons.org/licenses/by/ 95% CI = 0.84–1.14; p = 0.787). In conclusion, DM is associated with mortality in older women with 4.0/). NSTEACS, but not in men. J. Clin. Med. 2021, 10, 4403. https://doi.org/10.3390/jcm10194403 https://www.mdpi.com/journal/jcm J. Clin. Med. 2021, 10, 4403 2 of 9 Keywords: elderly; non-ST-segment elevation acute coronary syndromes; women; diabetes mellitus 1. Introduction Non-ST-segment elevation acute coronary syndrome (NSTEACS) constitutes one of the leading causes of hospital admissions and mortality in the elderly [1–5]. A great number of patients hospitalized for ACS are over 70 years of age, and women account for up to 30–40% of them [6,7]. Previous studies show women presenting with an acute coronary event are usually older, with a worse baseline clinical situation than men [8–10]. Such issues are associated with a worse prognosis [6,11,12], though women less often receive optimal medical therapies or an invasive approach [8,13]. However, different results have been reported in prior studies addressing the impact of sex on total and cardiovascular mortality in elderly patients with NSTEACS [8,14–17]. On the other hand, diabetes mellitus (DM) is often present in patients with acute coronary syndromes, associating a long-term excess risk of mortality [17–19]. Few studies have addressed to date the interaction between sex and DM in the prognosis of elderly patients with NSTEACS, and they have had contradictory results [20,21]. The present study comprised a pooled analysis of individual patient data that included elderly patients from 11 Spanish NSTEACS registries [22]. We aimed to study the prognostic influence of DM according to sex on 1-year mortality. 2. Material and Methods 2.1. Study Population This is an analysis of a retrospective study comprising 11 cohorts from Spanish NSTEACS registries. Registry investigators provided individual patient data to form a pooled patient database. Details of the cohorts are reported elsewhere [22]. Briefly, the study included patients aged 70 years or older with NSTEACS. Patients were managed according to standard practice in each hospital. Decisions on medical therapy and regarding invasive management during the index hospitalization were all left at the discretion of the attending physicians. 2.2. End Point The main end point of the study was all-cause mortality at a one-year follow-up. Infor- mation on mortality was collected from the hospital files or the regional mortality registry. 2.3. Statistical Analysis Continuous variables were expressed by mean ± one standard deviation, while categorical variables as absolute values (percentages). Baseline characteristics according to sex were compared by independent sample t-test, or chi-squared tests, as appropriate. A Cox regression model for the one-year mortality was initially built with variables chosen based on previous knowledge and biological plausibility. Hospital centers were included as strata to allow each center to have its own baseline hazard. From this initial set of covariates, a more parsimonious model was developed by backward elimination while simultaneously testing each continuous variable for departure from linearity (multivariable fractional polynomial procedure). If indicated, variables were transformed with the appropriate fractional polynomials. The final model for mortality included (all main effects) age (years), sex, hyperlipidemia, prior history of acute myocardial infarction, prior history of admission for heart failure, prior history of admission for stroke, prior history of admission for chronic obstructive pulmonary disease (COPD), anemia (WHO class), admission heart rate (bpm), systolic blood pressure (mmHg), left ventricular ejection fraction (LVEF, %), estimated glomerular filtration rate (eGFR, in mL/min/1.73 m2 ), Killip class ≥ II, ST- segment deviation, bundle branch block and Cath and PCI procedures performed at index admission. Risk estimates were expressed as hazard ratios (HRs) with 95% confidence J. Clin. Med. 2021, 10, 4403 3 of 9 intervals (CIs). Proportionality assumption for the hazard function over time was tested by means of Schoenfeld residuals. The discriminative ability of the multivariate model was evaluated with Harrell’s C-statistics. Based on prior knowledge that diabetes has shown a differential prognostic effect on mortality and other outcomes based on sex, we decided to explore such an interaction. Kaplan–Meier curves were estimated, stratifying the patient population according to sex and DM. Stata 15.1 (Stata Statistical Software, Release 15 (2017); StataCorp LP, College Station, Texas, TX, USA), was used for the main analyses. 2.4. Ethics The study complied with the Declaration of Helsinki, and the ethics committee of each participating hospital approved the study protocol. 3. Results Patient Population A total of 7211 patients were included in the study, including 2768 (38.4%) women. Baseline characteristics according to sex are shown in Table 1. Compared with men, women were significantly older (79.95 ± 5.75 vs. 78.45 ± 5.43 years, p = 0.0001) and more often had a history of previous hypertension, with no differences regarding DM or dyslipidemia. On the other hand, they less frequently had a prior history of arteriosclerotic cardiovascular disease (prior myocardial infarction, and history of percutaneous coronary intervention or coronary artery bypass graft; all p = 0.0001) and comorbidities such as peripheral artery disease or chronic pulmonary disease. Still, anemia and chronic kidney disease were both more common in women. Table 1. Baseline demographic and clinical characteristics according to sex. Total Male Female p (n = 7211) n = 4443 (61.6%) n = 2768 (38.4%) Baseline characteristics Age (years) 79.03 ± 5.6 78.45 ± 5.43 79.95 ± 5.75 <0.001 Diabetes 2874 (39.9) 1774 (39.9) 1100 (39.7) 0.863 Hypertension 5723 (79.4) 3420 (77) 2303 (83.1) <0.001 Dyslipidemia 4262 (59.1) 2641 (59.5) 1621 (58.5) 0.431 Smoking habit 621 (8.6%) 536 (12,1) 85 (3.1) <0.001 Prior myocardial infarction 1682 (23.3) 1186 (26.7) 496 (17.9) <0.001 Prior percutaneous coronary intervention 1334 (18.5) 943 (21.2) 391 (14.1) <0.001 Prior coronary artery bypass graft 573 (7.9) 461 (10.4) 112 (4) <0.001 Prior admission for heart failure 641 (8.9) 383 (8.6) 258 (9.3) 0.328 Admission systolic blood pressure, mmHg 141 ± 25 140 ± 24 143 ± 25 <0.001 Admission heart rate, bpm 79 ± 19 77 ± 18 80 ± 18 <0.001 Admission Killip class ≥ II 1889 (26.2) 1118 (25.2) 771 (27.8) 0.013 ST segment deviation 2638 (37) 1633 (36.8) 1005 (36.3) 0.688 Left bundle branch block or permanent pacemaker 1147 (16) 774 (17.4) 373 (13.5) <0.001 Troponin elevation 5319 (74) 3214 (72.4) 2105 (76) 0.001 Left ventricular ejection fraction, % 54 ± 11 53.7 ± 11 55.7 ± 10 <0.001 Comorbidities Prior stroke 831 (11.5) 524 (11.8) 307 (11.1) 0.363 Peripheral arterial disease 1006 (14) 791 (17.8) 215 (7.8) <0.001 Chronic pulmonary disease 1161 (16.1) 885 (19.9) 276 (10) <0.001 Hemoglobin on admission, gr/dl 12.9 ± 1.8 13.3 ± 1.9 12.6 ± 1.6 <0.001 J. Clin. Med. 2021, 10, 4403 4 of 9 Table 1. Cont. Total Male Female p (n = 7211) n = 4443 (61.6%) n = 2768 (38.4%) Glomerular filtration rate (mL/min) 66 ± 26 69 ± 27 61 ± 24 <0.001 Invasive management Invasive coronary angiography 6032 (84) 3844 (86.6) 2188 (79) <0.001 Percutaneous coronary intervention 3867 (53.6) 2552 (57.5) 1315 (47.5) <0.001 Coronary artery bypass graft 491 (6.8) 375 (8.4) 116 (4.2) <0.001 In-hospital revascularization 4339 (60.2) 2914 (65.6) 1425 (51.4) <0.001 Treatment at discharge Aspirin 6194 (90.6) 3882 (92.2) 2312 (88.1) <0.001 Clopidogrel 4341 (63.5) 2764 (65.6) 1577 (60.1) <0.001 Ticagrelor 327 (4.8) 238 (5.7) 89 (3.4) <0.001 Prasugrel 38 (0.6) 31 (0.7) 7 (0.3) 0.011 Statins 5938 (86.9) 3709 (88.1) 2229 (84.9) <0.001 On admission, women showed a worse clinical profile, with a higher heart rate and worse Killip class, though they had otherwise better left ventricular ejection fraction. Regarding invasive approach and in-hospital revascularization, they were both more often performed in men (p = 0.0001). At discharge, men more frequently received antiplatelet therapy and statins when compared with women. 1090 patients (15%) had died at the one-year follow-up, 702 (15.8%) men and 388 (14.6%) women, with no differences by sex in the univariate analysis. Table 2 shows the predictors of mortality at the one-year follow-up in the multivariable analysis. After adjusting for baseline differences, male sex was predictive of mortality (HR = 1.15, 95% CI 1.01 to 1.32, p = 0.035). Table 2. Predictors of mortality at one-year follow-up. Multivariate Analysis Univariate Analysis (without Interaction) Variable Hazard Ratio Hazard Ratio p Value p Value (95% CI) (95% CI) Age (per year) 1.07 (1.06–1.09) <0.001 1.04 (1.03–1.05) 0.0001 Male sex 1.12 (0.99–1.27) 0.075 1.15 (1.01–1.32) 0.035 Diabetes mellitus 1.53 (1.36–1.72) <0.001 1.12 (0.99–1.27) 0.071 Prior admission for heart failure 2.86 (2.47–3.32) <0.001 1.16 (0.98–1.36) 0.068 Prior stroke 1.67 (1.43–1.96) <0.001 1.13 (0.96–1.34) 0.121 Peripheral arterial disease 2.07 (1.80–2.38) <0.001 1.39 (1.20–1.61) 0.0001 Chronic pulmonary disease 1.67 (1.46–1.92) <0.001 1.28 (1.11–1.49) 0.001 Admission Killip class ≥ II 4.41 (3.91–4.97) <0.001 2.29 (1.99–2.64) 0.0001 ST segment deviation 1.95 (1.72–2.19) <0.001 1.61 (1.41–1.85) 0.0001 Left bundle branch block or permanent pacemaker 1.33 (1.15–1.55) <0.001 1.26 (1.05–1.51) 0.01 Left ventricular ejection fraction, % 0.96 (0.95–0.97) <0.001 0.989 (0.985–0.995) 0.0001 Admission systolic blood pressure, mmHg 0.985 (0.982–0.988) <0.001 0.991 (0.988–0.993) 0.0001 Admission heart rate, bpm 1.109 (1.017–1.022) <0.001 1.003 (1.0002–1.0066) 0.034 Anemia on admission 2.45 (2.17–2.76) <0.001 1.35 (1.19–1.55) 0.0001 Glomerular filtration rate (mL/min) 0.976 (0.974–0.979) <0.001 0.987 (0.984–0.990) 0.0001 Invasive coronary angiography 0.36 (0.32–0.41) <0.001 0.66 (0.56–0.78) 0.0001 Percutaneous coronary intervention 0.52 (0.46–0.59) <0.001 0.73 (0.63–0.84) 0.0001 Glomerular filtration rate (mL/min) 0.976 (0.974–0.979) <0.001 0.987 (0.984–0.990) 0.0001 Invasive coronary angiography 0.36 (0.32–0.41) <0.001 0.66 (0.56–0.78) 0.0001 Percutaneous Glomerular coronary filtration intervention rate (mL/min) 0.52 (0.46–0.59) <0.001<0.001 0.976 (0.974–0.979) 0.73 (0.63–0.84) 0.0001 0.0001 0.987 (0.984–0.990) Invasive coronary angiography 0.36 (0.32–0.41) <0.001 0.66 (0.56–0.78) 0.0001 J. Clin. Med. 2021, 10, 4403 Percutaneous coronary intervention As shown in the multivariable 0.52 (0.46–0.59) analysis for <0.001 one-year mortality, 0.73 (0.63–0.84) there was5 of 0.0001 a 9significa interaction between female sex and DM for one-year mortality (p = 0.002). Figure 1 show the AsKaplan–Meier curves afteranalysis shown in the multivariable stratifying patient population for one-year mortality, there according to sex and DM was a significant interaction Mortality between As shown was female higher in the sexdiabetics, in and analysis multivariable DM forbothone-year formen mortality and one-year women, (p =there mortality, 0.002). but wasFigure the effect 1was shows a significant greater interaction the between Kaplan–Meier female curves sex after and DM for stratifying one-year patient mortality population (p = 0.002). according women (p = 0.0001; stratified log-rank test). Indeed, after adjusting for other predictiv Figure to sex 1 shows and DM. the Kaplan–Meier Mortality was DM covariates, curves higherwas after stratifying instrongly diabetics, both patient menwith associated population and women,according mortality but the to in women sex effect and (HR:was DM. Mor-CI greater 1.45, 95% in = 1.1 tality women was (p =higher 0.0001;in diabetics, stratified both men log-rank and test).women, Indeed, but the after effect adjustingwas greater for other in women predictive 1.78; p < 0.001), while it was not in men (HR: 0.98, 95% CI = 0.84–1.14; p = 0.787) (Figure 2 (p = 0.0001;DM covariates, stratified log-rank associated was strongly test). Indeed, aftermortality with adjustingin forwomen other predictive (HR: 1.45, covariates, 95% CI =DM 1.18– was strongly associated with mortality in women (HR: 1.45, 95% CI = 1.18–1.78; 1.78; p < 0.001), while it was not in men (HR: 0.98, 95% CI = 0.84–1.14; p = 0.787) (Figure 2). p < 0.001), while it was not in men (HR: 0.98, 95% CI = 0.84–1.14; p = 0.787) (Figure 2). Figure Figure 1. Kaplan–Meier 1. Kaplan–Meier curves curves for one-year for one-year mortality mortality after stratifying after stratifying patient population patient population according accordin Figure 1. Kaplan–Meier curves for one-year mortality after stratifying patient population according toto sex sex and and Diabetes Diabetes mellitus. mellitus. to sex and Diabetes mellitus. Figure 2.2.Independent Figure Figure predictors 2. Independent Independent of of all-cause predictors predictors mortality. of all-cause all-cause mortality. mortality. On the other hand, age, prior stroke, peripheral artery disease, admission Killip class ≥ II, ST-segment deviation, left ventricular ejection fraction, admission systolic blood J. Clin. Med. 2021, 10, 4403 6 of 9 pressure, admission heart rate, anemia on admission, glomerular filtration rate and invasive coronary angiography were found to be independent predictors of mortality in patients with DM (Table S1, available in Supplementary Material). 4. Discussion The main findings of this study are: (1) male sex was significantly associated with worse prognosis in elderly patients with NSTEACS; (2) the prognostic impact of DM in all-cause mortality was only seen in women. Women constitute a great proportion of elderly patients with ACS. However, they are often underrepresented in large clinical trials [23–25]. In accordance with previous studies, women in our series were significantly older, and age per se has been shown to be associated with a worse prognosis [8–10]. A prior history of hypertension, together with higher blood pressure on admission, were both more often found in women, and such factors were associated with better outcomes at the one-year follow-up [17]. Instead, smoking and a history of prior coronary or peripheral artery disease were all more frequent in men and both issues related to worse clinical results [14,17,26]. Additionally, women showed a worse clinical profile on admission, with higher heart rate and Killip class (both issues significantly related to one-year mortality, the latter with the higher hazard ratio in the multivariable analysis) [8]. Conditions such as anemia and chronic kidney disease were both more frequent in women, findings similar to those previously reported, and they are also associated with a worse prognosis [8,15]. On the other hand, left ventricular ejection fraction was significantly lower in men. Despite the above, however, an invasive approach and in-hospital revascularization were both more often performed in men, as previously reported [6,8,15,26,27]. Moreover, revascularization has been associated with lower short-term mortality in elderly patients with NSTEACS [28]. In our study, several conditions were found to be independently associated with a worse prognosis in the multivariable analysis, as described in previous studies [8]. Male sex was associated with higher one-year mortality but, remarkably, an interaction was found between female sex and DM, in such a way that the presence of DM conferred a much worse prognosis in elderly women with NSTEAC when compared with men with DM. Different studies have demonstrated a long-term excess risk of mortality associated with this comorbidity following NSTEACS, independent of other factors such as other cardiovascular risk factors or therapies [17–19]. From a pathophysiological point of view, differences regarding cardiovascular outcomes have been described between men and women with DM, since microvascular complications seem to be more frequent in men and macrovascular complications are the leading cause of both morbidity and mortality in women [29,30]. In addition, differences in management and treatment of cardiovascular risk factors have been suggested in patients with DM, substantially worse in women, thus associating with a more adverse cardiovascular profile and further events [29]. In this regard, women in our study less frequently received antiplatelet therapy and statins at discharge, similar to findings reported in previous studies [15,31]. Additionally, consistent with previous findings [28], an invasive approach, especially when performed early after admission, was significantly associated with lower mortality at the one-year follow-up in our series. Prior studies addressing the impact of revascularization in elderly patients with NSTEACS have demonstrated an obvious benefit in this clinical setting, as it is associated with lower in-hospital mortality [8,26,27,32] regardless of the presence of DM [32]. How- ever, this strategy was less often performed in women in our series, something already reported in previous studies. In the study by Vogel et al. [8], DM was also significantly associated with conservative management, but only in men. These features, altogether, strengthen previous studies demonstrating women with DM show a more adverse cardio- vascular risk profile which, combined with receiving standard treatment less often, entail worse prognoses [33]. Few studies have addressed to date the interaction between sex and DM in the prognosis of patients with NSTEACS. Koek et al. included more than 20,000 patients J. Clin. Med. 2021, 10, 4403 7 of 9 with a first myocardial infarction (mean age much lower than that of our series, 33% women, 9.3% DM) and found no sex differences in short and long-term mortality [20]. On the other hand, the study by Icks et al., using data from the population-based MON- ICA/KORA Myocardial Infarction Registry (the study population was limited to patients aged 25–74 years old), included 16,478 patients with a first fatal or non-fatal myocardial infarction (with and without ST-segment elevation) between 1985 and 2009 (mean age 62 years, 71% male, 29% with DM), and they showed a strong relationship between DM and short and long-term mortality after a first ACS, relatively higher in women, somehow in line with our findings [21]. Of note, patients included in that study were much younger than those of our series (mean age 79 years, 38.4% women) and had no documented pre- vious coronary artery disease. Additionally, there are some temporary differences in the definition of myocardial infarction, according to different guidelines, and, importantly, data regarding revascularization are not shown. These issues, together with a much more robust multivariable analysis, make our study more solid and our results more generalizable. On the other hand, in another scenario such as acute heart failure with preserved left ventricular ejection fraction, diabetes conferred a higher risk of mortality in women [34]. Recently, Alkhouli et al. found adjusted odds of death for women vs. men varied by age in this setting, with a more pronounced negative impact of female sex on most outcomes in young and middle-aged women [35], thus reinforcing our findings. Our study has some limitations. First, this is a retrospective study; thus, selection bias cannot be ruled out, as in all observational registries. Second, since our study com- prises a pooled patient database from 11 different cohorts, issues such as type or du- ration of diabetes, or its complications, were not available in all of them and were not included in the analysis. Moreover, for this reason, information about treatment at dis- charge other than antiplatelets and statins is not available in our study. Finally, conditions with prognostic impact in elderly women with NSTEACS, such as frailty and other geriatric syndromes [36–38], were not included in our study. In spite of these limitations, and to the best of our knowledge, this is the first study addressing the impact of the interaction between sex and DM in the prognosis of elderly patients with NSTEACS. Our study also retrieved interesting and novel data about the prognosis of DM according to sex in this clinical scenario. Improving clinical management of these patients may contribute to im- proving both their quality of life and outcomes, given the global prevalence of diabetes and vascular complications. Further studies are needed to confirm these findings. 5. Conclusions In conclusion, DM is associated with mortality in elderly women with NSTEACS, but not in men. Supplementary Materials: The following are available online at https://www.mdpi.com/article/ 10.3390/jcm10194403/s1, Table S1: Independent predictors of mortality in patients with diabetes mellitus in multivariate analysis. Author Contributions: Conceptualization, P.D.-V. and J.S.; methodology, P.D.-V., E.N. and J.S.; software, E.N. and J.S.; validation, E.N. and J.S.; formal analysis, E.N. and J.S.; investigation, P.D.-V., J.M.G.-A., S.R.-R., J.A.B., A.C., M.M.-S., A.B., F.M., J.M.R.-N., N.V.-I., G.L.A.S., B.C.-A., E.A.A., F.F., J.N., E.N., A.A.-S. and J.S.; resources, J.S.; data curation, J.S.; writing—original draft preparation, P.D.-V. and J.S.; writing—review and editing, P.D.-V., J.M.G.-A., S.R.-R., J.A.B., A.C., M.M.-S., A.B., F.M., J.M.R.-N., N.V.-I., G.L.A.S., B.C.-A., E.A.A., F.F., J.N., E.N., A.A.-S. and J.S.; visualization, P.D.-V., J.M.G.-A., S.R.-R., J.A.B., A.C., M.M.-S., A.B., F.M., J.M.R.-N., N.V.-I., G.L.A.S., B.C.-A., E.A.A., F.F., J.N., E.N., A.A.-S. and J.S.; supervision, P.D.-V. and J.S.; project administration, J.S. All authors have read and agreed to the published version of the manuscript. Funding: This work was supported by grants from the Spanish Ministry of Economy and Competi- tiveness through the Carlos III Health Institute: CIBER-CV 16/11/00420, Madrid, Spain. J. Clin. Med. 2021, 10, 4403 8 of 9 Institutional Review Board Statement: The study was conducted according to the guidelines of the Declaration of Helsinki, and the ethics committee of each participating hospital approved the study protocol. Informed Consent Statement: Patient consent was waived due to the retrospective nature of the study using hospital medical records. Data Availability Statement: The data presented in this study are available on request from the corresponding author. The data are not publicly available due to privacy and ethical reasons. Conflicts of Interest: Barrabés has received fees for educational activities from AstraZeneca and for consultancy from Bayer. Sanchis has received speaker fees from Abbott Vascular and Prosmédica. The remaining authors have nothing to disclose. 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