Combining glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) in patients with type 2 diabetes mellitus (T2DM).

Due to their cardiovascular protective effect, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) represent breakthrough therapies for type 2 diabetes mellitus (T2DM). In this review article, we discuss the mechanistic and clinical synergies that make the combined use of GLP-1RAs and SGLT2is appealing in patients with T2DM. Overall, the presented cumulative evidence supports the benefits of GLP-1RA plus SGLT2i combination therapy on metabolic-cardiovascular-renal disease in patients with T2DM, with a low hypoglycemia risk. Accordingly, we encourage the adoption of GLP-1RA plus SGLT2i combination therapy in patients with T2DM and established atherosclerotic cardiovascular disease (ASCVD) or multiple risk factors for ASCVD (i.e., age ≥ 55 years, overweight/obesity, dyslipidemia, hypertension, current tobacco use, left ventricular hypertrophy, and/or proteinuria). Regarding renal effects, the evidence of SGLT2is in preventing kidney failure is more abundant than for GLP-1RAs, which showed a beneficial effect on albuminuria but not on hard kidney endpoints. Hence, in case of persistent albuminuria and/or uncontrolled metabolic risks (i.e., inadequate glycemic control, hypertension, overweight/obesity) on SGLT2i therapy, GLP-1RAs should be considered as the preferential add-on therapy in T2DM patients with chronic kidney disease. Despite the potential clinical benefits of GLP-1RA plus SGLT2i combination therapy in patients with T2DM, several factors may delay this combination to become a common practice soon, such as reimbursement and costs associated with polypharmacy. Altogether, when administering GLP-1RA plus SGLT2i combination therapy, it is important to adopt an individualized approach to therapy taking into account individual preferences, costs and coverage, toxicity profile, consideration of kidney function and glucose-lowering efficacy, desire for weight loss, and comorbidities.

Characteristics of patients with atrial fibrillation treated with direct oral anticoagulants and new insights into inappropriate dosing: results from the French National Prospective Registry: PAFF.

AIMS: Since the introduction of direct oral anticoagulant (DOAC) for atrial fibrillation (AF) therapy, inappropriate and/or underdosing of these drugs has been a major clinical challenge. We evaluated the characteristics of patients with AF treated with inappropriate and low-dose DOACs. METHODS AND RESULTS: Patients with AF treated with inappropriate and low-dose DOACs from October 2021 to December 2021 were evaluated from the French National Prospective Registry (PAFF). We evaluated 1890 patients with AF receiving DOACs (apixaban 55%, dabigatran 7%, and rivaroxaban 38%). Inappropriate dosing was noted in 18% of the population. Patients with appropriate dosing had less comorbidities: younger age (75 ± 10 vs. 82 ± 8 years old, P < 0.0001), reduced chronic renal failure (26 vs. 61%, P < 0.0001), and lower CHA2DS2VASc and HASBLED scores (3 ± 2 vs. 4 ± 3, P < 0.0001; 2 ±1 vs. 2 ± 2, P < 0.0001), respectively. In multivariate analysis, older age (P < 0.0001) and a higher CHA2DS2VASc score (P = 0.0056) were independently associated with inappropriate DOAC dosing. Among 472 patients (27%) treated with low-dose rivaroxaban or apixaban, 46% were inappropriately underdosed. Patients inappropriately underdosed were younger (82.3 ± 8.4 vs. 85.9 ± 5.9 years, P < 0.0001) with less chronic renal disease (47 vs. 98%, P < 0.0001). However, these patients had higher rates of prior haemorrhagic events (18 vs. 10%, P = 0.01), clopidogrel use (11 vs. 3%, P = 0.0002), and apixaban prescription (74 vs. 50%, P < 0.0001). CONCLUSION: Within this large registry, DOACs were associated with inappropriate dosing in 18% of cases. Independent predictors of inappropriate dosing were high CHA2DS2VASc scores and older age. Moreover, 46% of patients treated with low-dose DOACs were inappropriately underdosed and more frequently in patients treated with apixaban.

Sex differences in arterial hypertension.

There is strong evidence that sex chromosomes and sex hormones influence blood pressure (BP) regulation, distribution of cardiovascular (CV) risk factors and co-morbidities differentially in females and males with essential arterial hypertension. The risk for CV disease increases at a lower BP level in females than in males, suggesting that sex-specific thresholds for diagnosis of hypertension may be reasonable. However, due to paucity of data, in particularly from specifically designed clinical trials, it is not yet known whether hypertension should be differently managed in females and males, including treatment goals and choice and dosages of antihypertensive drugs. Accordingly, this consensus document was conceived to provide a comprehensive overview of current knowledge on sex differences in essential hypertension including BP development over the life course, development of hypertension, pathophysiologic mechanisms regulating BP, interaction of BP with CV risk factors and co-morbidities, hypertension-mediated organ damage in the heart and the arteries, impact on incident CV disease, and differences in the effect of antihypertensive treatment. The consensus document also highlights areas where focused research is needed to advance sex-specific prevention and management of hypertension.

Hyperuricemia and Hypertension, Coronary Artery Disease, Kidney Disease: From Concept to Practice.

Since the publication of the Framingham Heart Study, which suggested that uric acid should no longer be associated with coronary heart disease after additional adjustment for cardiovascular disease risk factors, the number of publications challenging this statement has dramatically increased. The aim of this paper was to review and discuss the most recent studies addressing the possible relation between sustained elevated serum uric acid levels and the onset or worsening of cardiovascular and renal diseases. Original studies involving American teenagers clearly showed that serum uric acid levels were directly correlated with systolic and diastolic pressures, which has been confirmed in adult cohorts revealing a 2.21-fold increased risk of hypertension. Several studies involving patients with coronary artery disease support a role for serum uric acid level as a marker and/or predictor for future cardiovascular mortality and long-term adverse events in patients with coronary artery disease. Retrospective analyses have shown an inverse relationship between serum uric acid levels and renal function, and even a mild hyperuricemia has been shown to be associated with chronic kidney disease in patients with type 2 diabetes. Interventional studies, although of small size, showed that uric acid (UA)-lowering therapies induced a reduction of blood pressure in teenagers and a protective effect on renal function. Taken together, these studies support a role for high serum uric acid levels (>6 mg/dL or 60 mg/L) in hypertension-associated morbidities and should bring awareness to physicians with regards to patients with chronic hyperuricemia.

Management of lipid variables in primary cardiovascular prevention: A position paper from the Heart, Vessels and Metabolism Group of the French Society of Cardiology.

Low-density lipoprotein cholesterol has been established as a powerful cardiovascular risk factor; its reduction provides a clinical benefit in primary cardiovascular prevention, irrespective of the characteristics of the patients treated. It is useful to tailor low-density lipoprotein cholesterol targets according to the magnitude of cardiovascular risk (low, high or very high) in order to reduce the cardiovascular risk as fully as possible. In order to provide a uniform approach, it is necessary to propose recommendations for good practice, defining strategies for reducing low-density lipoprotein cholesterol. It is also necessary to know their merits, to analyse their practical limits and to propose adaptations, taking into account limitations and national specifics. This position paper aims to analyse the contribution and limits, as well as the adaptation to French practice, of 2019 and 2021 European Society of Cardiology recommendations for the management of lipid variables and cardiovascular prevention.

Late phase of COVID-19 pandemic in General Cardiology. A position paper of the ESC Council for Cardiology Practice.

Cardiovascular (CV) engagement in coronavirus disease 2019 (COVID-19) is a huge determinant of prognosis during the acute phase of the disease. However, little is known about the potential chronic implications of the late phase of COVID-19 and about the appropriate approach to these patients. Heart failure, type 1 and type 2 myocardial infarction, arrhythmias, myocarditis, pulmonary fibrosis, and thrombosis have been shown to be related to severe acute respiratory syndrome coronavirus 2 infection, and a 'long COVID-19' illness has been recognized with fatigue, chest pain, and dyspnoea among the most frequent symptoms reported after discharge from hospital. This paper focuses on some open questions that cardiologists are going to face during the next months in a general cardiology outpatient clinic, in particular how to evaluate a 'post-COVID' patient during follow-up of CV complications of the acute phase and how to manage new CV symptoms that could be the consequence, at least in part, of heart/vessels and/or lung involvement of the previous virus infection. Present symptoms and signs, history of previous CV disease (both preceding COVID-19 and occurring during viral infection), and specific laboratory and imaging measurements during the acute phase may be of interest in focusing on how to approach the clinical evaluation of a post-COVID patient and how to integrate in our standard of care the new information on COVID-19, possibly in a multidisciplinary view. Dealing with the increased COVID-associated CV risk burden and becoming acquainted with potential new e-cardiology approaches aimed at integrating the cardiology practice are relevant new challenges brought by severe acute respiratory syndrome coronavirus 2 infection and its sequelae.

Prevalence and management of uncontrolled hypertension in French patients aged over 80 years.

BACKGROUND: The rate of uncontrolled hypertensives aged >80 years is not well known. The available literature on this topic has used the threshold <140/90 mmHg, whereas there is now a consensus for a different target: systolic blood pressure (SBP)<150 mmHg. AIMS: This prospective observational population-based study sought to assess the frequency and management of uncontrolled hypertension in French patients aged ≥80 years. METHODS: Nine hundred and seventy-one treated hypertensive outpatients were evaluable (204 recruited by cardiologists, 767 by general practitioners [GPs]; mean age 84.8 ± 3.8 years; 57.8% women). RESULTS: The frequency of SBP ≥ 150 mmHg was 36.6% (44.6% in cardiologists' patients and 34.4% in GPs' patients). The frequency of satisfaction with SBP ≥ 150 mmHg was 22.0% for cardiologists (32.6% if diastolic blood pressure [DBP] <90 mmHg and 9.5% if ≥90 mmHg; P=0.008) and 30.4% for GPs (51.7% if DBP <90 mmHg and 13.2% if ≥90 mmHg; P<0.0001). Non-diabetic status (for cardiologists) and DBP <90 mmHg (for cardiologists and GPs) were independent determinants of SBP being considered acceptable. Accordingly, in patients with an SBP level ≥ 150 mmHg that was considered too high, treatment was reinforced more often if DBP was ≥90 mmHg (82.3%) than <90 mmHg (68.5%). CONCLUSION: In France, hypertension is uncontrolled in more than one in three elderly hypertensives. Physicians are aware that SBP should be lowered to <150 mmHg in patients aged>80 years, but when the target is not reached they are less likely to increase treatment if DBP is <90 mmHg.

Epidemiology of atrial fibrillation in France: extrapolation of international epidemiological data to France and analysis of French hospitalization data.

The prevalence of atrial fibrillation is steadily increasing throughout the world because of ageing populations and better management of coronary heart disease. An international literature review was conducted to estimate the prevalence and incidence of atrial fibrillation in France. A review of the literature on comorbidities was also performed. Finally, French mortality and hospitalization data were analysed using the PMSI database. The prevalence of atrial fibrillation is estimated to be between 600,000 and 1 million people; of these, two-thirds are aged >75 years. The incidence is estimated at between 110,000 and 230,000 new cases per year. In 2008, 412,000 hospitalized patients had a diagnosis of atrial fibrillation; this figure increased by 26% in the 3-year period between 2005 and 2008. These findings highlight the importance of targeting therapy, of upstream therapy, and of therapy that provides clear clinical and economic advantages over the well-established reductions already achieved in atrial fibrillation morbidity, mortality and cost. In addition, new prevention strategies should be developed, particularly secondary prevention strategies in patients with cardiovascular diseases.

First evaluation using a validated scale of the risk of congestive heart failure among hypertensive patients treated by general practitioners (O-PREDICT survey).

BACKGROUND: Routine management of hypertensive adults is based on assessment of risk factors for coronary artery disease; risk factors for heart failure (HF) remain poorly investigated despite the key role of hypertension in HF development. AIM: To assess the components of HF risk in hypertensive adults in primary care, compare physicians' estimations of HF and global cardiovascular risks with established calculation algorithms, and assess the concordance of these algorithms. METHODS: O-PREDICT was a transverse, observational, multicentre French survey conducted in 2006 among general practitioners who included the first hypertensive, non-HF patient seen in each of three age classes (<60, 60-70, >70 years). Estimations of HF and global cardiovascular risks (at 4 and 10 years, respectively) were performed subjectively during the consultation and calculated a posteriori according to algorithms from the Framingham cohort and the European SCORE database, respectively. For each of these methods, patients were stratified into four risk categories (i.e., no, low, moderate, high). RESULTS: One thousand five hundred and thirty seven physicians recruited 4523 patients (61% men; 64.5+/-10.9 years; systolic blood pressure 149.9+/-15.4 mmHg); most (67.2%) patients had one or two cardiovascular/HF risk factors (dyslipidaemia 48.8%, left ventricular hypertrophy 25.3%, diabetes 18.8%, coronary artery disease 8.8%, valvulopathy 6.1%); the number increased with advancing age and in men versus women. According to the Framingham algorithm, the risk of HF (mean 5.4+/-8.5%; 13.4% of patients at high risk) increased with advancing age (p<0.001), nearly doubling for each decade increase. According to the European SCORE system, global cardiovascular risk (mean 5.4+/-4.3%) was moderate or elevated in 48.1% of patients. Concordance between physicians' estimations and theoretical calculations for HF and global risks was poor, as was concordance between algorithms (kappa(w)=0.28, 0.12, 0.11, respectively). CONCLUSION: More than one in 10 hypertensive patients seen in primary care is at high risk of HF at 4 years according to the Framingham model; this algorithm appears to offer additional information to that provided by the SCORE system. Physicians' estimations of risks correlated poorly with algorithm calculations, suggesting that the use of these tools in general practice should be encouraged.

Predictors of long-term use of evidence-based therapies after non-ST-segment elevation acute coronary syndrome. The S-Témoin survey.

BACKGROUND: We evaluated correlates of prolonged use of evidence-based therapies in patients discharged after non-ST-segment elevation acute coronary syndrome (NSTE ACS). METHODS: 598 cardiologists enrolled 2443 patients at outpatient clinics 2-12 months after discharge for NSTE ACS. The use of cardiac medications for secondary prevention (antiplatelets, beta-blockers, angiotensin-converting enzymes, and statins) was evaluated. RESULTS: A total of 2386 (97.7%) patients were on either antiplatelet monotherapy (n=623, 26.1%) or combination therapy (n=1763, 73.9%) at follow-up. Combination antiplatelet therapy declined by 23 percentage points (82.3% to 59.4%) 9-12 months after discharge, whereas use of other cardiac medications remained constant or increased. After multivariable analysis, the strongest predictors of combination antiplatelet therapy were PCI with a stent (odds ratio [OR] 3.75, 95% confidence interval [CI] 2.12-6.67), drug-eluting stents (OR 3.25, 95% CI 1.73-6.08), late PCI (OR 3.21, 95% CI 2.12-4.87) and statins at discharge (OR 1.98, 95% CI 1.40-2.80). Among the independent predictors of beta-blocker and statin use were extent of coronary artery disease and cardiac medications prescribed at discharge. CONCLUSIONS: After NSTE ACS, implementation of recommendations on long-term use of evidence-based therapies depends largely on in-hospital management. A variety of clinical characteristics are also predictive of long-term use.