Epidemiology of heart failure in diabetes: a disease in disguise.

Left ventricular diastolic dysfunction (LVDD) without symptoms, and heart failure (HF) with preserved ejection fraction (HFpEF) represent the most common phenotypes of HF in individuals with type 2 diabetes mellitus, and are more common than HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction (HFmrEF) and left ventricular systolic dysfunction (LVSD) in these individuals. However, diagnostic criteria for HF have changed over the years, resulting in heterogeneity in the prevalence/incidence rates reported in different studies. We aimed to give an overview of the diagnosis and epidemiology of HF in type 2 diabetes, using both a narrative and systematic review approach; we focus narratively on diagnosing (using the 2021 European Society of Cardiology [ESC] guidelines) and screening for HF in type 2 diabetes. We performed an updated (2016-October 2022) systematic review and meta-analysis of studies reporting the prevalence and incidence of HF subtypes in adults ≥18 years with type 2 diabetes, using echocardiographic data. Embase and MEDLINE databases were searched and data were assessed using random-effects meta-analyses, with findings presented as forest plots. From the 5015 studies found, 209 were screened using the full-text article. In total, 57 studies were included, together with 29 studies that were identified in a prior meta-analysis; these studies reported on the prevalence of LVSD (n=25 studies, 24,460 individuals), LVDD (n=65 studies, 25,729 individuals), HFrEF (n=4 studies, 4090 individuals), HFmrEF (n=2 studies, 2442 individuals) and/or HFpEF (n=8 studies, 5292 individuals), and on HF incidence (n=7 studies, 17,935 individuals). Using Hoy et al's risk-of-bias tool, we found that the studies included generally had a high risk of bias. They showed a prevalence of 43% (95% CI 37%, 50%) for LVDD, 17% (95% CI 7%, 35%) for HFpEF, 6% (95% CI 3%, 10%) for LVSD, 7% (95% CI 3%, 15%) for HFrEF, and 12% (95% CI 7%, 22%) for HFmrEF. For LVDD, grade I was found to be most prevalent. Additionally, we reported a higher incidence rate of HFpEF (7% [95% CI 4%, 11%]) than HFrEF 4% [95% CI 3%, 7%]). The evidence is limited by the heterogeneity of the diagnostic criteria over the years. The systematic section of this review provides new insights on the prevalence/incidence of HF in type 2 diabetes, unveiling a large pre-clinical target group with LVDD/HFpEF in which disease progression could be halted by early recognition and treatment.Registration PROSPERO ID CRD42022368035.

Association between lower extremity arterial calcification and coronary arterial calcification in a population at increased risk of cardiovascular disease.

INTRODUCTION: There is conflicting evidence whether lower extremity arterial calcification coincides with coronary arterial calcification (CAC). The aims of this study were to investigate the associations between (1) femoral and crural calcification with CAC, and (2) femoral and crural calcification pattern with CAC. RESEARCH DESIGN AND METHODS: This cross-sectional study included 405 individuals (74% men, 62.6±10.9 years) from the ARTEMIS cohort study at high risk of cardiovascular disease (CVD) who underwent a CT scan of the femoral, crural and coronary arteries. High CVD risk was defined as history/presence of cerebrovascular disease, coronary artery disease, abdominal aortic aneurysm, renal artery stenosis, peripheral artery disease or CVD risk factors: diabetes mellitus type 2, hypertension, hyperlipidemia. Calcification score within each arterial bed was expressed in Agatston units. Dominant calcification patterns (intimal, medial, absent/indistinguishable) were determined via a CT-guided histologically validated scoring algorithm. Multivariable-adjusted multinomial logistic regression analyses were used. Replication was performed in an independent population of individuals with diabetes mellitus type 2 (Early-HFpEF cohort study). RESULTS: Every 100-point increase in femoral and crural calcification score was associated with 1.23 (95% CI=1.09 to 1.37, p<0.001) and 1.28 (95% CI=1.11 to 1.47, p=0.001) times higher odds of having CAC within tertile 3 (high) versus tertile 1 (low), respectively. The association appeared stronger for crural versus femoral arteries. Moreover, the presence of femoral intimal (OR=10.81, 95% CI=4.23 to 27.62, p<0.001), femoral medial (OR=10.37, 95% CI=3.92 to 27.38, p<0.001) and crural intimal (OR=6.70, 95% CI=2.73 to 16.43, p<0.001) calcification patterns were associated with higher odds of having CAC within tertile 3 versus tertile 1, independently from concomitant calcification score. This association appeared stronger for intimal versus medial calcification patterns. The replication analysis yielded similar results. CONCLUSIONS: Higher femoral and crural calcification scores were associated with higher CAC. Moreover, the presence of femoral intimal, femoral medial and crural intimal calcification patterns was associated with increased CAC. It appears that arterial calcification is a systemic process which occurs simultaneously in various arterial beds.

Causal Association of Cardiovascular Risk Factors and Lifestyle Behaviors With Peripheral Artery Disease: A Mendelian Randomization Approach.

Background We investigated the causal associations between the genetic liability to cardiovascular and lifestyle risk factors and peripheral artery disease (PAD), using a Mendelian randomization approach. Methods and Results We performed a 2-sample inverse-variance weighted Mendelian randomization analysis, multiple sensitivity analyses to assess pleiotropy and multivariate Mendelian randomization analyses to assess mediating/confounding factors. European-ancestry genomic summary data (P<5×10-8) for type 2 diabetes, lipid-fractions, smoking, alcohol and coffee consumption, physical activity, sleep, and education level were selected. Genetic associations with PAD were extracted from the Million-Veteran-Program genome-wide association studies (cases=31 307, controls=211 753, 72% European-ancestry) and the GoLEAD-SUMMIT genome-wide association studies (11 independent genome-wide association studies, European-ancestry, cases=12 086, controls=449 548). Associations were categorized as robust (Bonferroni-significant (P<0.00294), consistent over PAD-cohorts/sensitivity analyses), suggestive (P value: 0.00294-0.05, associations in 1 PAD-cohort/inconsistent sensitivity analyses) or not present. Robust evidence for genetic liability to type 2 diabetes, smoking, insomnia, and inverse associations for higher education level with PAD were found. Suggestive evidence for the genetic liability to higher low-density lipoprotein cholesterol, triglyceride-levels, alcohol consumption, and inverse associations for high-density lipoprotein cholesterol, and increased sleep duration were found. No associations were found for physical activity and coffee consumption. However, effects fully attenuated for low-density lipoprotein cholesterol and triglycerides after correcting for apoB, and for insomnia after correcting for body mass index and lipid-fractions. Nonsignificant attenuation by potential mediators was observed for education level and type 2 diabetes. Conclusions Detrimental effects of smoking and type 2 diabetes, but not of low-density lipoprotein cholesterol and triglycerides, on PAD were confirmed. Lower education level and insomnia were identified as novel risk factors for PAD; however, complete mediation for insomnia and incomplete mediation for education level by downstream risk factors was observed.

Alcohol Consumption and Cardiovascular Disease Risk: Placing New Data in Context.

PURPOSE OF REVIEW: A clear link between excessive alcohol consumption and cardiovascular disease (CVD) has been established, but no consensus exists on the effects of moderate alcohol consumption on CVD. RECENT FINDINGS: A lower risk of coronary heart disease and myocardial infarction among moderate drinkers compared to abstainers has been consistently observed in epidemiological studies and meta-analyses of these studies. However, ambiguity remains on the effect of alcohol on other CVDs and all-cause mortality. Short-term randomized controlled trials (RCT) have identified potentially beneficial effects of alcohol consumption on cardiovascular risk factors, but studies investigating genetic polymorphisms that influence alcohol consumption (i.e., Mendelian randomization) have yielded inconclusive results. To date, a long-term RCT providing causal evidence is lacking but urgently needed. Triangulation of evidence from different study designs, including long-term RCTs, pragmatic trials and the evaluation of policy measures, combined will lead to the best available evidence.

An elevated ankle-brachial index is not a valid proxy for peripheral medial arterial calcification.

BACKGROUND AND AIMS: The ankle brachial index (ABI) is often used as a proxy for medial arterial calcification (MAC) in studies investigating MAC as a cardiovascular risk factor, but evidence supporting this hypothesis is sparse. This study aims to investigate the use of an elevated ABI as proxy for MAC, as visualized with computed tomography (CT). METHODS: Cross-sectional data of 718 participants with, or at risk of cardiovascular disease was used. The ABI was calculated using cutoffs >1.4 and > 1.3. The presence of MAC was assessed in the crural and femoral arteries by CT imaging. Modified Poisson regression was used to assess the association between an elevated ABI and the presence of MAC, and test characteristics were calculated. RESULTS: MAC was found in 25.0% of participants. An ABI >1.4 was found in 8.7% of participants, of whom 45.2% had MAC. An elevated ABI was significantly associated with the presence of MAC (RR 1.74, CI: 1.26-2.40). However, poor positive specific agreement (23.3%, CI: 13.9-34.3), sensitivity (15.7%, CI: 10.4-21.1) and positive predictive value (45.2%, CI: 32.8-57.5) were found. Despite good specificity (93.6%, CI: 91.6-95.7) the area under the receiving operator curve remained poor (54.7%, CI: 51.8-57.6). Negative specific agreement (84.5%, CI: 81.4-87.0) and negative predictive value (77.0%, CI: 73.7-80.2) were acceptable. CONCLUSIONS: An elevated ABI is insufficient to serve as a true diagnostic proxy for MAC. Studies that have drawn conclusions on the association between MAC and cardiovascular disease, solely based on the ABI, are likely to underestimate the found effects.