Abstract 4146218: Sex differences in cardiovascular-kidney-metabolic health for degenerative valvular heart disease

The cardiovascular-kidney-metabolic (CKM) health approach emphasizes the importance of multidisciplinary early-stage disease prevention. This study aimed to explore sex differences in CKM risk factors associated with common degenerative valvular heart disease (VHD). A total of 436,184 participants (54.4% women; mean age, 58 years) free of VHD or heart failure at baseline and with complete information about CKM risk factors were included from the UK Biobank cohort. We assessed sex differences in hazard ratios (HRs) and population-attributable risk (PAR) for incident VHD and VHD-related interventions or mortality, focusing on five CKM risk factors: hypertension, diabetes, obesity, hypertriglyceridemia, and chronic kidney disease (CKD). At baseline, 81.06% of participants had one or more CKM risk factors: 75.61% had hypertension, 4.80% had diabetes, 24.14% had obesity, 22.26% had hypertriglyceridemia, and 2.32% had CKD. Over a median follow-up period of 13.80 years, incidences of aortic valve stenosis (AS), aortic valve regurgitation (AR), and mitral valve regurgitation (MR) were 11.18 and 5.42, 3.64 and 2.19, and 10.39 and 6.94 events per 10,000 person-years for men and women, respectively. Hypertension was consistently the largest attributable risk factor for incident VHD in both sexes, with PARs of 29.07% and 25.17% for AS, 24.21% and 16.51% for AR, and 19.55% and 13.01% for MR in women and men, respectively. Compared to men, women had higher risks of AS with obesity (HR: 1.17 [1.04-1.32]), AR with CKD (1.59 [1.01-2.49]), and MR with either hypertension (1.25 [1.07-1.47]) or hypertriglyceridemia (1.22 [1.07-1.39]). Tailoring the prioritization of CKM risk factors based on gender has the potential to enhance the effectiveness of VHD prevention strategies.

There are no effective medications to prevent the onset of degenerative valvular heart disease (VHD). Sweetened beverage consumption may contribute to the development of VHD by affecting metabolic disorders, systemic inflammation, and calcification processes. This study aimed to prospectively assess the association between sweetened beverage consumption and the risk of degenerative VHD. This prospective study included 167,801 participants from the UK Biobank who completed at least one dietary questionnaire. During a median follow-up of 14.53 years, 1,464 cases of aortic valve stenosis (AS) events, 584 cases of aortic valve regurgitation (AR) events, and 1,744 cases of mitral valve regurgitation (MR) events were recorded. Compared with non-consumers, participants consuming more than one drink per day of artificially sweetened beverages (ASBs) had a higher risk of AS (HR: 1.36, 95% CI: 1.10-1.68), AR (HR: 1.42, 95% CI: 1.02-2.00), MR (HR: 1.35, 95% CI: 1.10-1.64). Similarly, the consumption of more than one drink of sugar-sweetened beverages (SSBs) was associated with an increased incidence of MR (HR: 1.47, 95% CI: 1.22-1.77). In contrast, no significant association was observed between the consumption of natural juices (NJs) and VHD risk. Results for VHD-related interventions, deaths, or cardiovascular events were largely consistent. Substituting SSBs or ASBs per day with NJs was associated with a reduced risk of MR (HR: 0.83, 95% CI: 0.72-0.94) events or AS (HR: 0.81, 95% CI: 0.69-0.94) events, respectively. Lower consumption of SSBs or ASBs may reduce the risk of degenerative VHD and VHD-related events.

Asthma has been associated with the development and progression of various cardiovascular diseases but its relationship with degenerative valvular heart disease (VHD) remains unclear. This study investigated the association between asthma and incident degenerative VHD, including aortic stenosis (AS), aortic regurgitation (AR), mitral regurgitation (MR) and pulmonary regurgitation (PR). We analysed 483 735 participants from the UK Biobank (median age 56.5 years; 45.2% male) who were free of VHD at baseline. Asthma status was self-reported at recruitment. Incident VHD was ascertained through hospital admission and mortality records using International Classification of Diseases, Tenth Revision codes. Cox proportional hazards models were used to estimate HRs and 95% CIs for each VHD subtype, adjusting for demographic, lifestyle and clinical covariates. Sensitivity analyses accounted for asthma medications, duration of asthma and competing risks. Over a median follow-up of 13.8 years, 5388 participants developed AS, 2650 AR, 6088 MR and 821 PR. Asthma was associated with increased risk of AS (HR 1.31; 95% CI 1.21 to 1.41), AR (HR 1.24; 95% CI 1.11 to 1.39), MR (HR 1.19; 95% CI 1.10 to 1.28) and PR (HR 1.34; 95% CI 1.10 to 1.62). The association with AR was attenuated after adjusting for asthma medications (HR 1.12; 95% CI 0.97 to 1.30). Results were robust across multiple sensitivity analyses, including adjustment for asthma duration and exclusion of participants with pre-existing cardiovascular disease. Asthma is independently associated with a modestly increased risk of several degenerative VHDs, particularly aortic and mitral valve diseases. These findings suggest a potential shared inflammatory pathway and highlight the need for heightened cardiovascular surveillance in individuals with asthma.

Accumulating evidence indicates that degenerative valvular heart disease (VHD) and rheumatoid arthritis (RA) share overlapping risk factors and intersecting inflammatory processes; however, their interrelationship remains insufficiently explored. Among 492 745 UK Biobank participants without VHD at baseline, Cox proportional hazards models were conducted to assess the association between prevalent RA and new-onset degenerative VHD, with sequential adjustments for demographic factors, lifestyle variables, and comorbidities. The end points of degenerative VHD in this study included 8 subtypes: aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid stenosis, tricuspid regurgitation, pulmonary stenosis, and pulmonary regurgitation. Among participants with RA (n=6673), 359 cases of degenerative VHD were recorded over a median follow-up of 13.71 (interquartile range, 12.71-14.55) years, compared with 13 518 cases in those without RA (n=486 072) over a median follow-up of 13.78 (interquartile range, 12.96-14.51) years. After full adjustment, RA was significantly associated with a higher risk of 3 types of new-onset degenerative VHD: aortic stenosis (hazard ratio [HR], 1.64 [95% CI, 1.40-1.92]), aortic regurgitation (HR, 1.69 [95% CI, 1.34-2.13]), and mitral regurgitation (HR, 1.54 [95% CI, 1.32-1.81]), while no significant association was observed between RA and other degenerative VHD subtypes. Moreover, sex subgroup analyses revealed an interaction between sex and RA in the occurrence of aortic stenosis (P for interaction=0.02) and mitral regurgitation (P for interaction=0.04), indicating a higher risk in women. The presence of RA indicated an elevated risk of new-onset degenerative aortic stenosis, aortic regurgitation, and mitral regurgitation, which required further investigation and better disease management.

Valvular heart disease (VHD) is a common clinical condition in geriatric-related cardiovascular diseases that is connected to heart dysfunction. Atrial fibrillation (AF) is the most frequent arrhythmia. Considering these two common clinical conditions, so far no sufficient data on the relationship between degenerative VHD and non-valvular atrial fibrillation (NVAF). We aimed to explore the relationship between valvular structure and biochemistry of nonvalvular AF and degenerative valvular heart disease in the elderly. In our study, 234 VHD patients who were diagnosis evaluated by transthoracic echocardiography were enrolled in this retrospective study from January 2015 and December 2018. Significant valvular diseases were defined according to ACC/AHA Classification as any moderate or severe mitral regurgitation (MR), aortic regurgitation (AR), tricuspid stenosis, regurgitation, or aortic stenosis (AS). Data on relevant laboratory indicators were also collected. A total of 234 patients with degenerative VHD were enrolled, of whom 81 had NVAF and 153 had sinus rhythm. Gender, smoking history, and some comorbidities, such as coronary artery disease, diabetes, and renal dysfunction, did not differ significantly between the two groups, but there were significant differences in age and hypertension {79 [74-83] vs. 70 [65-79] years} After propensity-score matching (PSM), we identified 68 VHD patients with NVAF and 68 VHD patients without NVAF. The NVAF + VHD had higher low-density lipoprotein (LDL) cholesterol (2.94±0.84 vs. 2.26±1.33 mmol/L, P=0.001), lower high-density lipoprotein (HDL) cholesterol [1.03 (0.89-1.34) vs. 1.56 (0.99-2.71) mmol/L, P<0.001], and higher uric acid (UA) (438.18±145.83 vs. 376.67±148.03 µmol/L, P=0.02) than the VHD group. The ejection fraction (EF) of the NVAF + VHD group was lower than that of the VHD group {63 [51-68] vs. 66 [62-69], P=0.013}. In addition, the left atrial size, MR, and calcification of the NVAF + VHD group were higher than those of the VHD group. Pronounced MR, valve calcification and hyperlipidemia were more likely in VHD patients with NVAF. These structures and biomarkers changes maybe important clinical parameters for disease prevention and management, which indicate early drug intervention to AF and hyperlipidemia is necessary.

The relationship between physical frailty, age-related conditions, and the incidence of degenerative valvular heart disease (VHD) remains unclear. This study aimed to investigate the potential association between physical frailty and the development of degenerative VHD. Participants from the UK Biobank who were initially free of VHD and heart failure were categorized into 3 groups based on the frailty phenotype: non-frailty, pre-frailty, and frailty. The frailty phenotype was determined by evaluating the following 5 components: weight loss, exhaustion, reduced physical activity, slow gait speed, and low grip strength. The incidence of degenerative VHD, including mitral valve regurgitation (MR), aortic valve regurgitation (AR), and aortic valve stenosis (AS), was assessed using hospital admission or death registries. Among the 331642 participants, 11885 (3.6%) exhibited frailty and 143379 (43.2%) were categorized as pre-frailty. During a median follow-up of 13.8 years, there were 3684 MR, 1205 AR, and 3166 AS events. Compared to non-frailty participants, those with pre-frailty and frailty showed significantly increased risks for MR (hazard ratio [HR], HRpre-frailty:1.19, 95% confidence interval [CI]: 1.11-1.28; HRfrailty: 1.50, 95% CI: 1.30-1.74), AR (HRpre-frailty:1.19, 95% CI: 1.05-1.34; HRfrailty: 1.58, 95% CI: 1.22-2.04), and AS (HRpre-frailty:1.19, 95% CI: 1.11-1.29; HRfrailty: 1.74, 95% CI: 1.51-2.00). Among the 5 components, slow gait speed showed the strongest association with the risk of various types of VHD (HRMR: 1.50, 95% CI: 1.34-1.65; HRAR: 1.50, 95% CI: 1.24-1.80; HRAS: 1.46, 95% CI: 1.32-1.62), followed by exhaustion, low grip strength, and weight loss. Pre-frailty and frailty were associated with a higher risk of all 3 types of degenerative VHD. Early detection and intervention for pre-frailty and frailty in middle-aged and older individuals may assist in preventing or delaying the onset of degenerative VHD.

Wearable device-measured moderate to vigorous physical activity and risk of degenerative aortic valve stenosis.

Hypothesis: This study aimed to examine the impact of moderate-to-vigorous intensity physical activity (MVPA) on the prevention of left-sided degenerative valvular heart disease (VHD) among middle-aged adults. Methods: In the UK biobank study, data from wrist-worn accelerometer and physical activity questionnaires were utilized to assess the role of MVPA volume on the incidence of aortic valve stenosis (AS), aortic valve regurgitation (AR), and mitral valve regurgitation (MR). The primary cohort involved 90,865 participants ( median 8.1-year follow-up period) without prevalent VHD and heart failure, who wore accelerometers for one week. The validation cohort included 397,335 participants (median 13.8-year follow-up period) who completed physical activity questionnaires. MVPA volume was categorized according to the American Heart Association’s recommendation. Results: Accelerometer-measured MVPA showed a curvilinear relationship with reduced AS risk, with the risk reduction plateauing above 300 min/week. Compared to no MVPA, those engaging in 150-299 minutes of MVPA per week showed the most significant risk reduction [1-149 min/week: adjusted hazard ratio (HR), 0.79 (0.58, 1.08); 150-299 min/week: HR, 0.52 (0.36, 0.75); ≥300 min/week: HR, 0.57 (0.39, 0.83)]. Similar results were found when repeating the above analyses in self-reported MVPA cohort, with a relatively smaller reduction in HR ratio [150-299 min/week: HR, 0.81 (0.73, 0.91)]. No significant association was found between the MVPA volume and the risk of AR and MR in both cohorts. Conclusions: Meeting current MVPA recommendations (150-300 min/week) was associated with the lowest AS risk. Targeting adherence to accelerometer-measured MVPA thresholds may enhance AS risk reduction. Additionally, MVPA showed limited effectiveness in preventing valvular regurgitation, indicating distinct mechanisms between stenotic lesions and regurgitation lesions in degenerative VHD.

Degenerative valvular heart disease, the most common form of valve disease in the Western world, can lead to aortic stenosis (AS) or mitral regurgitation (MR). In current guidelines for the management of patients with degenerative valvular disease, surgical intervention is recommended at the onset of symptoms or in the presence of left ventricular systolic impairment. Whether surgery is appropriate for asymptomatic patients remains a controversial issue. We argue the case for early pre-emptive intervention in selected, asymptomatic individuals with AS or MR, drawing on contemporary perioperative data, predictors of disease progression, and studies of the natural history of degenerative valvular heart disease.

Recent evidence indicates that degenerative valvular heart disease (VHD) and psoriasis share overlapping risk factors and simultaneous presence of inflammation, yet this relationship has not been thoroughly explored. Drawing on the prospective cohort data from the UK Biobank, baseline information on psoriasis and the incidence of eight specific types of degenerative VHD-aortic stenosis (AS), aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid stenosis, tricuspid regurgitation, pulmonary stenosis, and pulmonary regurgitation-during the follow-up period were recorded. Cox proportional hazards models were conducted to estimate the association between psoriasis and the risk of degenerative VHD, adjusted for demographic indicators, lifestyle factors, comorbidities, and medication. A total of 494 510 participants were included in the study. Among the participants without psoriasis, 13 672 events of degenerative VHD were observed during a median follow-up of 13.78 years, yielding an incidence rate of 2.14 per 1000 person-years. In contrast, in the psoriasis group (n=10 917), 422 events of degenerative VHD were reported during a median follow-up of 13.70 years, corresponding to an incidence rate of 2.93 per 1000 person-years. After fully adjusting, participants with psoriasis had a significantly increased risk of AS (hazard ratio, 1.24; 95% confidence interval, 1.07-1.43), yet no significant associations were observed between psoriasis and the risk of other degenerative valve diseases. In sex subgroup analyses, there was an interaction between sex and psoriasis in the occurrence of AS (P for interaction=0.039), suggesting a high risk in women. Psoriasis was significantly associated with the risk of new-onset AS and may be more distinct in females, while no significant associations were observed between psoriasis and the risk of developing other degenerative valve diseases.

Aim The present study was aimed at investigating the prevalence, incidence, progression, and prognosis of degenerative valvular heart disease (DVHD) in permanent residents aged ≥65 years from Guangzhou, China. Methods This was a prospective study based on community population. Over a 3-year span, we conducted repeated questionnaires, blood tests, and echocardiographic and electrocardiogram examinations (2018) of a random sample of initially 3538 subjects. Results The prevalence of DVHD increased with age, average values being 30.6%, 49.2%, and 62.9% in 65-74, 75-84, and ≥85 years of age, respectively. The incidence rate was 1.7%/year. Aortic stenosis was the result of DVHD, and the mean transvalvular pressure gradient increased by 5.6 mmHg/year. The increase of mild aortic stenosis was lower than that of more severe disease, showing a nonlinear development of gradient, but with great individual variations. Mortality was significantly increased in the DVHD group (HR = 2.49). Risk factors for higher mortality included age (χ2 = 1.9, P < 0.05), renal insufficiency (χ2 = 12.5, P < 0.01), atrial fibrillation (χ2 = 12.2, P < 0.01), mitral regurgitation (χ2 = 1.8, P < 0.05), and tricuspid regurgitation (χ2 = 6.7, P < 0.05) in a DVHD population. Conclusions DVHD was highly prevalent among residents in southern China. With the progression of the disease, the mean transvalvular pressure gradient accelerated. DVHD was an independent predictor of death, and the mortality was higher in those with older age, renal insufficiency, atrial fibrillation, mitral regurgitation, and tricuspid regurgitation.

2012 ACCF/AATS/SCAI/STS Expert Consensus Document on Transcatheter Aortic Valve Replacement: Developed in collaboration with the American Heart Association, American Society of Echocardiography, European Association for Cardio-Thoracic Surgery, Heart Failure Society of America, Mended Hearts, Society of Cardiovascular Anesthesiologists, Society of Cardiovascular Computed Tomography, and Society for Cardiovascular Magnetic Resonance

Morphologic features of the normal and abnormal mitral valve

Due to an ageing population and increasing survival from concurrent diseases, the burden of left-sided degenerative valvular heart disease is expected to increase over time. This study aims at determining the temporal trends in incidence rates at the population level and examines whether there are socioeconomic differences. A total of 133 209 patients were identified with a first-time diagnosis of aortic stenosis (AS), mitral regurgitation (MR), or aortic regurgitation (AR) in the Danish National Patient Registry in the 2000-17 period. Incidence rates (per 100 000 person-years) doubled over the period for AS (57 in 2000-02; 114 in 2015-17) and for AR (22 in 2000-02; 41 in 2015-17) and remained the same for MR (38 in both 2000-02 and 2015-17). Incidence rates increased rapidly with increasing age, most markedly for AS. Men had a higher risk of being affected [relative risk (RR) 1.69 for AS, 1.19 for MR, 1.35 for AR]. Compared to high-level education, patients with medium- and low-level education had a higher risk of being affected (RR 1.18 for AS medium level and 1.47 for AS low level; 1.03 for MR medium level and 1.14 for MR low level; 1.03 for AR medium level and 1.18 for AR low level). For AS and AR, the incidence rates doubled, while the incidence rates remained at the same level for MR. The risk of being affected increased with advanced age and male gender. Patients with low-level education had a higher risk of being affected compared to patients with high-level education, especially among patients with AS.

Acute severe valvular regurgitation is a surgical emergency, but accurate and timely diagnosis can be difficult. Although cardiovascular collapse is a common presentation, examination findings to suggest acute regurgitation may be subtle, and the clinical presentation may be nonspecific. Consequently, the presentation of acute valvular regurgitation may be mistaken for other acute conditions, such as sepsis, pneumonia, or nonvalvular heart failure. Although acute regurgitation may affect any valve, acute regurgitation of the left-sided valves is more common and has greater clinical impact than acute regurgitation of right-sided valves. Data to guide appropriate management of patients with acute regurgitation are sparse; there are no randomized trials, and much of the literature describes either small series or the experiences of specific centers. Despite these limitations, the available data are sufficient to allow identification of general principles as well as development of applicable guidelines from both the American College of Cardiology/American Heart Association and European Society of Cardiology. The guidelines recommend valve surgery for symptomatic patients with aortic or mitral regurgitation, including those with acute regurgitation.1–3 The data and guidelines emphasize overarching clinical principles, including the need for a high clinical suspicion of acute regurgitation, timely use of echocardiography, and, in the majority of patients, rapid progression to surgery. Causes of acute regurgitation overlap with causes of chronic regurgitation and vary depending on the valve affected (Table 1). Endocarditis may affect either the aortic or mitral valve, whereas other causes are unique to the specific valve involved. The majority of causes of acute regurgitation present as an acute or subacute event. However, acute regurgitation can occur in patients with chronic regurgitation, when regurgitant severity is exacerbated by factors such as coronary ischemia, chordal rupture, or leaflet perforation from endocarditis. Acute regurgitation of either the aortic or mitral valve may result from procedural …