Association between the insulin resistance and all-cause mortality in patients with moderate and severe aortic stenosis: a retrospective cohort study.

BACKGROUND: The triglyceride-glucose (TyG) index is a reliable surrogate marker of insulin resistance (IR). However, whether the TyG index has prognostic value in patients with moderate to severe aortic stenosis (AS) remains unclear. METHODS: This study enrolled 317 patients with moderate to severe AS at the First Affiliated Hospital of Sun Yat-Sen University. The patients were grouped according to the cut-off value of the TyG index. Cox regression with Firth's penalized maximum likelihood method and restricted cubic splines regression were conducted to assess the association between the TyG index and all-cause mortality. The added value of the TyG index included in the traditional risk factors model for outcome prediction was also analyzed. RESULTS: Among 317 patients (mean age 67.70 years, 62.8% male), there was 84 all-cause mortality during a median 38.07 months follow-up. After fully adjusting for confounders, a per-unit increase in the TyG index was associated with a 62% higher all-cause mortality risk (HR 1.622, 95% CI 1.086-2.416, p = 0.018). The restricted cubic splines regression model revealed a linear association between the TyG index and the risk of all-cause mortality (p for nonlinearity = 0.632). The addition of the TyG index in the basic risk model has an incremental effect on the prediction of mortality [C-statistic change from 0.755 to 0.768; continuous net reclassification improvement (95% CI): 0.299 (0.051-0.546), p = 0.017; integrated discrimination improvement: 0.017 (0.001-0.033), p = 0.044]. CONCLUSIONS: Higher IR assessed by the TyG index was associated with a higher risk of all-cause mortality in patients with moderate and severe AS.

Low-Density Lipoprotein Cholesterol, Type 2 Diabetes and Progression of Aortic Stenosis: The RED-CARPET Heart Valve Subgroup Cohort Study.

Background: Low-density lipoprotein cholesterol (LDL-C) and type 2 diabetes (T2DM) are both independent risk factors for aortic stenosis (AS). In AS patients, whether LDL-C or T2DM is associated with fast AS progression (FASP) and their interaction is unknown. This study aims to test the hypothesis that there is a heightened risk of FASP when elevated LDL-C coexists with T2DM. Methods: The Real-world Data of Cardiometabolic Protections (RED-CARPET) study enrolled participants with mild (peak aortic velocity = 2-3 m/s), moderate (3-4 m/s) and severe ( ≥ 4 m/s) AS between January 2015 and December 2020 at a single center. Participants were further stratified by baseline LDL-C joint T2DM, follow-up echocardiography was performed after 6 months, and the primary outcome was FASP, defined as the annual change in aortic peak velocity ( ≥ 0.3 m/s/year). Results: Among the 170 participants included, 45.3% had mild AS, 41.2% had moderate AS, and 13.5% had severe AS. The mean age was 66.84 ± 12.64 years, and 64.1% were women. During the follow-up period of 2.60 ± 1.43 years, 35 (20.6%) cases of FASP were identified. Using non-T2DM with LDL-C < 2.15 mmol/L as reference, FASP risk was 1.30 [odds ratio (OR), 95% CI (0.99-7.78, p = 0.167)] for non-T2DM with LDL-C 2.15-3.14 mmol/L, 1.60 [OR, 95% CI (1.17-3.29, p = 0.040)] for non-T2DM with LDL-C ≥ 3.14 mmol/L, 2.21 [OR, 95% CI (0.49-4.32, p = 0.527)] for T2DM with LDL-C < 2.15 mmol/L, 2.67 [OR, 95% CI (1.65-7.10, p = 0.004)] for T2DM with LDL-C 2.15-3.14 mmol/L, and 3.20 [OR, 95% CI (1.07-5.34, p = 0.022)] for T2DM with LDL-C ≥ 3.14 mmol/L. Conclusions: LDL-C joint T2DM was associated with FASP. This investigation suggests that fast progression of AS may develop if LDL-C is poorly managed in T2DM. Additional research is needed to validate this finding and explore the possible biological mechanism to improve the cardiometabolic management of T2DM and seek possible prevention for AS progression for this population. Clinical Trial Registration: ChiCTR2000039901 (https://www.chictr.org.cn).

Visceral adiposity index and the risk of heart failure, late-life cardiac structure, and function in ARIC study.

BACKGROUND: It is well established that obesity is associated with the risk of heart failure (HF). However, the data about relationship between visceral fat and the risk of HF are limited. AIMS: We aim to evaluate the association between visceral obesity assessed by visceral adiposity index (VAI) and incident HF and left ventricular (LV) structure and function in Atherosclerosis Risk in Communities (ARIC) study. METHODS: We included 12 161 participants (aged 54.1 ± 5.8 years) free of history of HF and coronary heart disease at baseline (1987-89) in ARIC study. We used multivariable Cox hazard regression models to assess the association between the VAI and incident HF. We further explored the effects of the VAI on LV geometry and function among 4817 participants with echocardiographic data using multivariable linear regression analysis and multinomial logistic regression. RESULTS: During a median follow-up of 22.5 years, a total of 1904 (15.7%) participants developed HF. After adjustment for traditional HF risk factors, 1 unit increase in the baseline VAI was associated with an 8% higher risk of incident HF [hazard ratio (HR): 1.08, 95% confidence interval (CI): 1.06-1.11]. Results were similar when participants were categorized by VAI tertiles. Compared with participants in the lowest tertile of VAI, those in the second tertile and third tertile had a greater risk of incident HF [HR (95% CI): 1.19 (1.05-1.34) and 1.42 (1.26-1.61), respectively]. For the analyses of the HF subtypes, the higher VAI was only associated with the risk of HF with preserved ejection fraction, not with HF with reduced ejection fraction. In addition, the greater VAI was associated with worse LV diastolic function and abnormal LV geometry including concentric remodelling, concentric hypertrophy, and eccentric hypertrophy. CONCLUSION: This study shows that higher VAI was independently associated with the increased risk of incident HF and abnormal LV geometry and LV diastolic dysfunction.

We investigated the relationship between visceral adiposity index (VAI) and incident heart failure (HF) in 12 161 participants and further evaluated the possible effect of the VAI on late-life left ventricular (LV) structure and function in 4817 participants who underwent echocardiography examination at Visit 5 in Atherosclerosis Risk in Communities study.Our study found that VAI, a simple alternative indicator of visceral obesity, was positively associated with the risk of HF.Our results shown that VAI was significantly associated with abnormal LV geometry and worse LV diastolic function in late life.

Targeting efficacy of spironolactone in patients with heart failure with preserved ejection fraction: the TOPCAT study.

AIMS: We aimed to explore the heterogeneous treatment effects (HTEs) for spironolactone treatment in patients with Heart failure with preserved ejection fraction (HFpEF) and examine the efficacy and safety of spironolactone medication, ensuring a better individualized therapy. METHODS AND RESULTS: We used the causal forest algorithm to discover the heterogeneous treatment effects (HTEs) from patients in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. Cox regressions were performed to assess the hazard ratios (HRs) of spironolactone medication for cardiovascular death and drug discontinuation in each group. The causal forest model revealed three representative covariates and participants were partitioned into four subgroups which were Group 1 (baseline BMI ≤ 31.71 kg/m2 and baseline ALP ≤ 80 U/L, n = 759); Group 2 (BMI ≤ 31.71 kg/m2 and ALP > 80 U/L, n = 1088); Group 3 (BMI > 31.71 kg/m2 , and WBC ≤ 6.6 cells/µL, n = 633); Group 4 (BMI > 31.71 kg/m2 and WBC > 6.6 cells/µL, n = 832), respectively. In the four subgroups, spironolactone therapy reduced the risk of cardiovascular death in high-risk group (Group 4) with both high BMI and WBC count (HR: 0.76; 95% CI 0.58 to 0.99; P = 0.045) but increased the risk in low-risk group (Group 1) with both low BMI and ALP (HR: 1.45; 95% CI 1.02 to 2.07; P = 0.041; P for interaction = 0.020) but showed similar risk of drug discontinuation (P for interaction = 0.498). CONCLUSION: Our study manifested the HTEs of spironolactone in patients with HFpEF. Spironolactone treatment in HFpEF patients is feasible and effective in patients with high BMI and WBC while harmful in patients with low BMI and ALP. Machine learning model could be meaningful for improved categorization of patients with HFpEF, ensuring a better individualized therapy in the clinical setting.

Association between serum cystatin C level and hemodynamically significant aortic stenosis: a prospective cohort study.

BACKGROUND: Cystatin C (CysC) is a cysteine protease inhibitor involved in proteins catabolism and plays an essential role in human vascular pathophysiology. CysC may also increase the risk of aortic stenosis (AS), but limited studies have reported on this association. This study aimed to investigate if elevated serum CysC levels are associated with hemodynamically significant AS. METHODS: Serum CysC levels were estimated in 4,791 participants, samples were collected in 1990-1992. The study population was divided into quintile groups. Follow-up continued in 2011-2013 when participants returned for echocardiography examination. Incidence of aortic valve disease (AVD) was ascertained by Doppler echocardiography through the end of 2013. AVD defined in hemodynamic progression was assessed and classified as aortic sclerosis, mild stenosis, and moderate-to-severe stenosis. RESULTS: Overall, a total of 4,791 participants (mean age: 54.8 ± 5.0 years, females: 57.6%, blacks: 8.2%) were included in this study. During a follow-up of 21 years, we identified 736 cases (15.4%) of aortic sclerosis, 194 cases (4.0%) of mild stenosis, and 42 cases (0.7%) of moderate-to-severe stenosis. Compared with serum CysC levels within individual quintile groups, the odds ratio (OR) was per standard deviation associated with an increased incidence of AVD (OR = 1.15, 95% CI: 1.05-1.26,P = 0.002). CONCLUSIONS: In this large population-based study, an increased serum CysC levels is independently associated with the incidence of hemodynamically significant AS. However, this association appears not to extend to patients with extremely high serum CysC levels and necessitate further investigation.