Introduction
Aortic valve diseases (AVD) represent a common type of heart valve disease. Historically, the AVD was primarily recognized as congenital or rheumatic, as observed epidemiological studies. However, the landscape has evolved, with degenerative causes becoming more prevalent due to the rapidly ageing population in Korea.1, 2 Preventing AVD in light of these factors is challenging. With the increasing use of clinical examinations such as echocardiography, non-symptomatic or minor AVD cases are now more frequently detected than in the past. Hence, it is crucial to reevaluate survival rates (SR) and death risk associated with AVD at this junction. By ‘junction’, we refer to the critical point in time where the prevalence of degenerative causes is increasing while the incidence of rheumatic causes is decreasing, necessitating a comprehensive reassessment of disease management strategies. The incidence of acute rheumatic fever (ARF) has shown a dramatic decline in high-income countries since the start of the 20th century, possibly due to improved healthcare access or to changes in streptococcal infections.3, 4 The Global Burden of Disease study reported a 26% decline in death due to rheumatic heart disease (RHD) worldwide from 1990 to 2013, with a 55% reduction in age-standardized mortality.5, 6 Few studies have explored the epidemiology of AVD, including the rheumatic type, in East Asian populations. This study aims to assess incidence, prevalence, SR and death risk for both non-rheumatic and rheumatic AVD using data from the Korean National Health Insurance Service (KNHIS) from 2006 through 2017.
Methods
Our study employed the methods and utilized data, including information presented in Tables 2 from the article titled ‘Temporal trends in incidence, prevalence, and death of aortic stenosis in Korea: A nationwide population-based study’ by Jang et al.2
Data source: KNHIS database
The KNHIS is the primary insurance provider for 97% of the Korean population, excluding those receiving medical aid. In 2015, the KNHIS database included records for 50 490 157 persons. The comprehensive database encompasses health insurance subscribers and Medicare recipients (excluding foreigners) and comprises four distinct databases: (1) a qualification database, (2) a medical check-up database, (3) a medical institution database, and (4) a treatment database, which encompasses disease types, disease code utilizing the ICD-10 classification and prescriptions. The treatment database has four categories: medicine, dentist, oriental medicine and pharmacy. For our analysis, we exclusively utilized the medicine database, incorporating variables from the qualifications database in conjunction with treatment.2, 7–9
Study population and diagnosis of AVD
The inclusion criteria of this study consisted of newly diagnosed AVD patients (non-rheumatic n = 85 177 and rheumatic n = 16 718) encompassing all age groups and both sexes, collected from the KNHIS records spanning the years from 2006 through 2017. Congenital heart disease including bicuspid aortic valve, was excluded during the study period. The dataset included primary diagnoses related to AVD, as classified under the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10), specifically codes I35 and I06. Newly diagnosed AVD was operationally defined using ICD-10 codes I35 and I06. To ensure the inclusion of only newly diagnosed AVD patients from the KNHIS database, cases of AVD diagnosed before the corresponding year were excluded. The breakdown of AVD subtypes included in the analysis was as follows: non-rheumatic aortic stenosis (AS, ICD-10: I35.0, n = 3773, male = 42.7%); non-rheumatic aortic insufficiency (AR, ICD-10: I35.1, n = 73 956, male = 36.8%); non-rheumatic aortic stenosis with insufficiency (ASAR, ICD-10: I35.2, n = 7448, male = 41.5%); rheumatic aortic stenosis (RAS, ICD-10: I06.0, n = 5315, male = 40.8%); rheumatic aortic insufficiency (RAR, ICD-10: I06.1, n = 8471, male = 33.3%); and rheumatic aortic stenosis with insufficiency (RASAR, ICD-10: I06.2, n = 2932, male = 33.9%).
Definition of variables
Age categories
Age categories were defined as follows: 0–9 years, 10–19 years, 20–29 years, 30–39 years, 40–49 years, 50–59 years, 60–69 years, 70–79 years and 80 years or older.
Income levels
We grouped individuals by income level based on their national health insurance premium, which served as a socioeconomic factor. Income levels were categorized as upper, medium and lower. Income quantiles are used to determine the income level of the target person through insurance premium information. Members of the same household share the same income decile. Income deciles are categorized into 20 groups based on the income levels of both employed insured individuals and self-employed individuals. The employee-insured charges insurance premiums based on annual income. On the other hand, members of the same household share the same income decile, which may include non-working individuals. Therefore, the income category reflects the total household income, which might appear higher than the actual per capita income when considering non-working members.
Comorbidities
Comorbidities were defined based on primary and secondary diagnoses and included the following conditions: hypertension (ICD-10: I10, I11, I12, I13, I15), diabetes mellitus (ICD-10: E10, E11 E12, E13, E14), dyslipidaemia (ICD-10: E78), myocardial infarction (ICD-10: I21, I22, I25.2), heart failure (ICD-10: I11.1, I50, I97.1), atrial fibrillation (ICD-10: I48.0), ischaemic stroke (ICD-10: I63, I64), haemorrhagic stroke (ICD-10: I60, I61, I62), transient ischaemic attack (ICD-10: G45), chronic kidney disease (ICD-10: N18, N19) and malignant neoplasm (ICD-10: C00-C97).2
Mortality data for the Korean population (2006–2018)
We used mortality data for the Korean population from 2006 to 2018. The reliability of this dataset is contingent upon the stringent requirements imposed on Korean citizens, mandating the submission of two crucial documents: death declaration and death certificate or corpse optometry report. We received only the cause and date of death from the Korea Statistics Promotion Institute in accordance with official procedures.2, 8 From the comprehensive set of information mandated by these requirements, our study obtained exclusively the cause and date of death, following official procedures.
Cause of death categories
In our analysis, we assessed primary causes of death based on the following ICD-10 codes: A00-B99; C00-C97; D00-D48 and D50-D89; F01-F99); H00-H59 and H60-H95; I00-I99; J00-J98; K00-K92; L00-L99; M00-M99; N00-N99; O00-O99; P00-P96; Q00-Q99; R00-R99; S00-T98; U00-U99; and not provided. These categories were used to classify and analyse the primary causes of death in our study. Specifically, when the cause of death fell under diseases of the circulatory system (ICD-10: I00–I99), we categorized it as a cardiovascular death.
Ethics statement
This study involving human participants underwent a thorough review and received approval from the Institutional Review Board of Samsung Medical Center (IRB File No. 2017-02-032). The Samsung Medical Center IRB, established in 1994, ensures adherence to international standards such as the ICH guidelines and GCP. It achieved full accreditation from the Association for the Accreditation of Human Research Protection Programs (AAHRPP) in June 2006, becoming the first IRB outside the United States to receive this recognition, underscoring its international credibility. Informed consent was exempted based on the assessment that the study was anonymized and posed minimal risk for the subject. The KNHIS data used in this study are anonymized and processed as secondary data on a national scale. Therefore, individual consent was not required as the data do not contain personally identifiable information. This exemption does not adversely affect the rights or well-being of the study subjects.
Statistical methods
Differences in characteristics were analysed using the Student's t-test or analysis of variance for continuous variables and the χ2-test for categorical variables. The age-standardized incidence and prevalence rates of AVD were computed using the direct method, with beneficiaries of health insurance from the Korean National Health Insurance Statistical Yearbook from 2006 through 2017. And we used the estimated Korean population in 2015 as a reference.1, 9, 10 Survival among AVD patients was compared by age group and sex employing the Kaplan–Meier method, and log-rank tests were conducted to analyse differences. For assessment of risk factors influencing survival, both simple and multiple Cox proportional hazards analyses were carried out. The variables included in these analyses were age, sex, and income level. All statistical analyses were conducted utilizing SAS software (version 9.4 for windows; SAS Institute Inc., Cary, NC, USA). Statistically significance was defined as a two-tailed P value of <0.05 for all comparisons.
Results
AVD overview
The total number of individuals with non-rheumatic and rheumatic AVD was 101 895 with 37.2% being male. The proportion of non-rheumatic AVD and rheumatic AVD was 83.5% and 16.5%, respectively. Among both non-rheumatic and rheumatic AVD cases, AR was the most prevalent (72.5%) (Table 1).
Table 1 The distribution of general characteristics and causes of death by sex among individuals with newly diagnostic aortic valve disease; aortic stenosis (AS), aortic insufficiency (AR) and aortic stenosis with insufficiency (ASAR).
| Variables | Non-rheumatic ( |
Rheumatic ( |
||||
| AS | AR | ASAR | RAS | RAR | RASAR | |
| mean ± SD, median (IQR), or number (percentage) | ||||||
| Age, years, mean (±SD) | 69.9 ± 15.3 | 67.5 ± 14.3 | 70.8 ± 13.5 | 69.5 ± 13.8 | 65.6 ± 14.5 | 67.7 ± 13.6 |
| median (interquartile range) | 73 (63, 80) | 70 (60, 78) | 73 (64, 80) | 72 (62, 79) | 68 (57, 76) | 70 (60, 77) |
| Age group, n (%) | ||||||
| 0–9 | 36 (0.95) | 371 (0.50) | 19 (0.26) | 20 (0.38) | 33 (0.39) | 7 (0.24) |
| 10–19 | 33 (0.87) | 409 (0.55) | 29 (0.39) | 20 (0.38) | 45 (0.53) | 7 (0.24) |
| 20–29 | 18 (0.48) | 630 (0.85) | 31 (0.42) | 27 (0.51) | 84 (0.99) | 21 (0.72) |
| 30–39 | 52 (1.38) | 1658 (2.24) | 115 (1.54) | 96 (1.81) | 293 (3.46) | 71 (2.42) |
| 40–49 | 171 (4.53) | 4438 (6.0) | 319 (4.28) | 268 (5.04) | 669 (7.90) | 196 (6.68) |
| 50–59 | 443 (11.7) | 10 275 (13.9) | 817 (10.9) | 654 (12.3) | 1324 (15.6) | 399 (13.6) |
| 60–69 | 751 (19.9) | 17 981 (24.3) | 1525 (20.4) | 1166 (21.9) | 2123 (25.0) | 676 (23.0) |
| 70–79 | 1228 (32.5) | 24 499 (33.1) | 2566 (34.4) | 1786 (33.6) | 2664 (31.4) | 1041 (35.5) |
| 80+ | 1041 (27.6) | 13 695 (18.5) | 2027 (27.2) | 1278 (24.0) | 1236 (14.5) | 514 (17.5) |
| Sex, male, n (%) | 1613 (42.7) | 27 271 (36.8) | 3094 (41.5) | 2169 (40.8) | 2825 (33.3) | 994 (33.9) |
| Income levela, n (%) | ||||||
| Upper | 1880 (48.5) | 34 857 (47.2) | 3534 (47.4) | 2506 (47.2) | 3774 (44.6) | 1309 (44.7) |
| Middle | 853 (22.6) | 17 400 (23.5) | 1721 (23.1) | 1204 (22.6) | 2091 (24.7) | 746 (25.4) |
| Lower | 1090 (28.9) | 21 699 (29.3) | 2193 (29.4) | 1605 (30.2) | 2606 (30.7) | 877 (29.9) |
| Comorbidities, n (%) | ||||||
| Hypertension | 1519 (40.3) | 36 599 (49.4) | 3484 (46.7) | 2300 (43.2) | 3679 (43.4) | 994 (33.9) |
| Diabetes mellitus | 357 (9.46) | 6712 (9.08) | 1004 (13.4) | 616 (11.5) | 569 (6.72) | 244 (8.32) |
| Dyslipidaemia | 491 (13.0) | 13 174 (17.8) | 1539 (20.6) | 1046 (19.6) | 1240 (14.6) | 408 (13.9) |
| Myocardial infarction | 76 (2.01) | 1278 (1.73) | 247 (3.32) | 142 (2.67) | 96 (1.13) | 32 (1.09) |
| Heart failure | 659 (17.4) | 10 150 (13.7) | 1283 (17.2) | 833 (15.6) | 993 (11.7) | 334 (11.3) |
| Atrial fibrillation | 304 (8.06) | 3728 (5.04) | 565 (7.59) | 358 (6.74) | 362 (4.27) | 136 (4.64) |
| Ischaemic stroke | 74 (1.96) | 2193 (2.97) | 262 (3.52) | 142 (2.67) | 209 (2.47) | 49 (1.67) |
| Haemorrhagic stroke | 6 (0.16) | 214 (0.29) | 20 (0.27) | 13 (0.24) | 16 (0.19) | 3 (0.10) |
| Transient ischaemic attack | 5 (0.13) | 409 (0.55) | 24 (0.32) | 17 (0.32) | 52 (0.61) | 5 (0.17) |
| Chronic kidney disease | 98 (2.60) | 987 (1.33) | 187 (2.51) | 94 (1.77) | 68 (0.80) | 31 (1.06) |
| Malignant neoplasm | 42 (1.11) | 1550 (2.10) | 126 (1.69) | 79 (1.49) | 125 (1.48) | 61 (2.08) |
| Death, n (%) | 1374 (36.4) | 18 815 (25.4) | 2712 (36.4) | 2078 (39.1) | 2215 (26.1) | 971 (33.1) |
| Cause of deathb, n (%) | ||||||
| Certain infections and parasitic diseases (A00-B99) | 22 (1.60) | 441 (2.34) | 49 (1.81) | 34 (1.64) | 61 (2.75) | 24 (2.47) |
| Malignant neoplasm (C00-C97) | 139 (10.3) | 3020 (16.1) | 302 (11.1) | 235 (11.3) | 327 (14.8) | 136 (14.0) |
| Neoplasm (D00-D48) and diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism (D50-D89) | 2 (0.14) | 139 (0.74) | 11 (0.41) | 18 (0.87) | 14 (0.63) | 8 (0.82) |
| Endocrine, nutritional, and metabolic diseases (E00-E90) | 44 (3.20) | 556 (2.96) | 92 (3.39) | 65 (3.13) | 54 (2.44) | 29 (2.99) |
| Mental and behavioural disorders (F01-F99) | 11 (0.80) | 224 (1.19) | 18 (0.66) | 11 (0.53) | 33 (1.49) | 7 (0.72) |
| Diseases of the nervous system (G00-G98) | 15 (1.09) | 410 (2.18) | 33 (1.22) | 18 (0.87) | 62 (2.80) | 9 (0.93) |
| Diseases of the eye and adnexa (H00-H59) and diseases of the ear and mastoid process (H60-H95) | 0 (0.00) | 1 (0.01) | 0 (0.00) | 0 (0.00) | 0 (0.00) | 0 (0.00) |
| Diseases of the circulatory system (I00-I99) | 627 (45.6) | 6382 (33.9) | 1149 (42.3) | 965 (46.4) | 797 (36.0) | 399 (41.1) |
| Diseases of the respiratory system (J00-J98) | 96 (6.99) | 1665 (8.85) | 207 (7.63) | 164 (7.89) | 192 (8.67) | 76 (7.83) |
| Diseases of the digestive system (K00-K92) | 39 (2.84) | 529 (2.81) | 72 (2.65) | 58 (2.79) | 56 (2.50) | 28 (2.88) |
| Diseases of the skin and subcutaneous tissue (L00-L98) | 3 (0.21) | 33 (0.18) | 1 (0.04) | 3 (0.15) | 3 (0.14) | 2 (0.21) |
| Diseases of the musculoskeletal system and connective tissue (M00-M99) | 5 (0.36) | 159 (0.85) | 14 (0.52) | 9 (0.45) | 18 (0.81) | 3 (0.31) |
| Diseases of the genitourinary system (N00-N98) | 50 (3.64) | 570 (3.03) | 107 (3.95) | 64 (3.13) | 51 (2.30) | 20 (2.06) |
| Pregnancy, childbirth and the puerperium (O00-O99) | 0 (0.00) | 2 (0.01) | 0 (0.00) | 0 (0.00) | 0 (0.00) | 0 (0.00) |
| Certain conditions originating in the perinatal period (P00-P96) | 0 (0.00) | 2 (0.01) | 0 (0.00) | 0 (0.00) | 0 (0.00) | 0 (0.00) |
| Congenital malformation, deformations and chromosomal abnormalities (Q00-Q99) | 3 (0.21) | 22 (0.12) | 4 (0.15) | 1 (0.05) | 4 (0.18) | 1 (0.10) |
| Symptoms, signs, and abnormal clinical and laboratory findings, not elsewhere classified (R00-R99) | 90 (6.55) | 1336 (7.10) | 168 (6.19) | 118 (5.68) | 145 (6.55) | 69 (7.11) |
| Injury, poisoning, and certain other consequences of external causes (S00-T98) | 34 (2.47) | 842 (4.48) | 96 (3.54) | 68 (3.27) | 125 (5.64) | 35 (3.60) |
| Codes for special purposes (U00-U99) | 0 (0.00) | 1 (0.01) | 0 (0.00) | 1 (0.05) | 0 (0.00) | 0 (0.00) |
| Not provided | 194 (14.1) | 2481 (13.2) | 389 (14.3) | 246 (11.8) | 273 (12.3) | 125 (12.9) |
Age distribution
The mean ages for patients with AS, AR, ASAR, RAS, RAR and RASAR were 69.9 (±15.3), 67.5 (±14.3), 70.8 (±13.5), 69.5 (±13.8), 65.6 (±14.5) and 67.7 (±13.6) years, respectively. The median ages for patients with AS, AR, ASAR, RAS, RAR and RASAR were 73, 73, 73, 72, 68.5 and 70 years, respectively. More than 70% of overall AVD patients were aged 60 years or older (Tables 1 and S1-1).
Comorbidities and socioeconomic status
The proportions of comorbidities among AVD patients were as follows: 33%–49% with hypertension, 6%–13% with diabetes mellitus, 12%–19% with dyslipidaemia, 1–3% with myocardial infarction, 11%–17% with heart failure, 4%–8% with atrial fibrillation, 1%–3% with ischaemic stroke, 0.1%–0.44% with haemorrhagic stroke, 0.1–0.6% with transient ischaemic attack, 0.8%–2.6% with chronic kidney disease and 1.11%–2.1% with malignant neoplasm. AVD patients were more prevalent in the upper socioeconomic group the middle or lower group. AS, ASAR, RAS and RASAR patients had around 33% death proportion while AR and RAR patients had around 25% death proportion. Diseases of the circulatory system were the leading cause of death among AVD patients, followed by malignant neoplasms (Tables 1 and S1-1).
Incidence and prevalence patterns
The age-standardized incidence of non-rheumatic AVD remained stable from 2006 through 2017, whereas the age-standardized prevalence of non-rheumatic AVD increased over the same decade. However, the age-standardized incidence and prevalence of rheumatic AVD decreased during this period. The age-standardized incidence and prevalence of AS, AR, ASAR, RAS, RAR and RASAR showed the highest in 80 years and over age group (Figure 1 and Tables S2-1–6, S3-1–6).
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Survival rates
The 10 year SRs for AS (49.2%), ASAR (50.2%) and RAS (51.4%) were lower than those for AR (64.5%), RAR (69.2%) and RASAR (63.8%) (Figure 2 and Table S4). The 10 year SRs of male and female was 50.3% and 48.3% in AS (P = non-significance, NS), 63.2% and 65.3% in AR (P < 0.001), 52.2% and 48.8% in ASAR (P = NS), 52.6% and 50.6% in RAS (P = NS), 66.1% and 70.6% in RAR (P < 0.001) and 54.0% and 68.45% in RASAR (P < 0.001). The 10 year SRs for all AVD across age groups showed a significant difference (P < 0.001). Additionally, the 10 year SRs for all AVD related to cardiovascular death were lower than those for non-cardiovascular death (P < 0.001) (Figure S1 and Table S4).
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Death risk
The risk of death related to AVD was higher in older individuals, males, those with lower income levels, diabetes mellitus, myocardial infarction, heart failure, atrial fibrillation, stroke, chronic kidney disease or malignant neoplasm. The adjusted hazard ratio (HR) for AS was 9.08 [95% confidence interval (CI) 1.27, 64.7] in 70–79 year olds and 22.7 (95% CI 3.18, 161.9) in individuals 80 years of age or older, 1.46 (95% CI 1.31, 1.63) in males, 1.19 (95% CI 1.03, 1.37) in the medium income level, 1.32 (95% CI 1.17, 1.49) in the lower income level, 1.57 (95% CI 1.16, 2.13) in myocardial infarction (MI), 1.63 (95% CI 1.44, 1.85) in heart failure, 1.52 (95% CI 1.08, 2.13) in ischaemic stroke, 3.26 (95% CI 1.20, 8.85) in haemorrhagic stroke, 2.51 (95% CI 1.94, 3.25) in chronic kidney disease and 2.33 (95% CI 1.64, 3.31) in malignancy. The adjusted HR for AR was 2.35 (95% CI 1.53, 3.63) in 40–49 years, 2.94 (95% CI 1.92, 8.41) in 50–59 years, 5.52 (95% CI 3.63, 8.41) in 60–69 years, 14.6 (95% CI 9.61, 22.2) in 70–79 year olds; and 38.8 (95% CI 25.5, 59.1) in individuals 80 years of age or older, 1.52 (95% CI 1.48, 1.57) in males, 1.13 (95% CI 1.09, 1.18) in the medium income level and 1.31 (95% CI 1.26, 1.35) in the lower income level. And the adjusted HR for ASAR was 18.4 (95% CI 2.59, 131.3) in 70–79 year olds and 47.2 (95% CI 6.64, 336.0) in individuals 80 years of age or older, 1.29 (95% CI 1.19, 1.39) in males and 1.30 (95% CI 1.25, 1.42) in the lower income level (Table 2).
Table 2 Adjusted hazard ratio [HR and 95% confidence interval (CI)] in aortic valve diseases.a
| Variables | AS | AR | ASAR | RAS | RAR | RASAR |
| Adjusted HR and 95% CI | ||||||
| Age group, years | ||||||
| 0–9 | — | 0.54 (0.20, 1.44) | — | — | 0.53 (0.06, 4.59) | — |
| 10–19 | — | 0.61 (0.27, 1.37) | 0.88 (0.05, 14.1) | — | 1.17 (0.28, 4.91) | — |
| 20–29 | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 |
| 30–39 | 1.07 (0.11, 9.61) | 1.55 (0.97, 2.48) | 1.43 (0.17, 11.7) | 0.77 (0.08, 7.40) | 0.89 (0.32, 2.47) | 0.43 (0.07, 2.58) |
| 40–49 | 1.48 (0.19, 11.1) | 2.35 (1.53, 3.63)* | 2.71 (0.37, 19.8) | 2.42 (0.32, 17.9) | 1.12 (0.44, 2.85) | 0.82 (0.19, 3.60) |
| 50–59 | 1.53 (0.27, 11.1) | 2.94 (1.92, 8.41)* | 4.15 (0.58, 29.7) | 3.66 (0.51, 26.3) | 1.91 (0.78, 4.69) | 1.19 (0.28, 4.92) |
| 60–69 | 4.09 (0.57, 29.2) | 5.52 (3.63, 8.41)* | 6.53 (0.91, 46.5) | 8.38 (1.17, 59.7)** | 4.19 (1.73, 10.1)** | 2.72 (0.67, 11.0) |
| 70–79 | 9.08 (1.27, 64.7)** | 14.6 (9.61, 22.2)* | 18.4 (2.59, 131.3)** | 21.2 (2.98, 151.0)** | 9.68 (4.01, 23.3)* | 6.08 (1.51, 24.4)** |
| 80+ | 22.7 (3.18, 161.9)** | 38.8 (25.5, 59.1)* | 47.2 (6.64, 336.0)* | 49.1 (6.89, 349.5)* | 28.7 (11.8, 69.3)* | 20.2 (5.03, 81.6)* |
| Sex, male vs. female | 1.46 (1.31, 1.63)* | 1.52 (1.48, 1.57)* | 1.29 (1.19, 1.39)* | 1.40 (1.28, 1.53)* | 1.62 (1.48, 1.77)* | 2.12 (1.85, 2.42)* |
| Income level* | ||||||
| Upper | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 |
| Middle | 1.19 (1.03, 1.37)** | 1.13 (1.09, 1.18)* | 1.09 (0.99, 1.21) | 1.17 (1.04, 1.31)** | 1.12 (1.01, 1.25)** | 1.23 (1.04, 1.45)** |
| Lower | 1.32 (1.17, 1.49)* | 1.31 (1.26, 1.35)* | 1.30 (1.19, 1.42)* | 1.13 (1.02, 1.24)** | 1.34 (1.21, 1.47)* | 1.34 (1.16, 1.55)* |
| Hypertension | 0.86 (0.77, 0.97)** | 0.90 (0.87, 0.92)* | 0.87 (0.80, 0.94)* | 0.90 (0.82, 0.98)** | 1.02 (0.94, 1.12) | 0.97 (0.84, 1.12) |
| Diabetes mellitus | 1.17 (0.99, 1.39) | 1.27 (1.21, 1.33)* | 1.22 (1.09, 1.36)* | 1.23 (1.08, 1.39)** | 1.49 (1.29, 1.72)* | 1.30 (1.05, 1.61)** |
| Dyslipidaemia | 0.67 (0.56, 0.81)* | 0.67 (0.64, 0.70)* | 0.70 (0.63, 0.78)* | 0.85 (0.75, 0.95)** | 0.64 (0.55, 0.74)* | 0.90 (0.73, 1.10) |
| Myocardial infarction | 1.57 (1.16, 2.13)** | 1.73 (1.59, 1.87)* | 1.79 (1.51, 2.12)* | 1.44 (1.15, 1.80)** | 1.61 (1.19, 2.19)** | 2.23 (1.35, 3.67)** |
| Heart failure | 1.63 (1.44, 1.85)* | 1.58 (1.52, 1.63)* | 1.52 (1.39, 1.66)* | 1.59 (1.43, 1.77)* | 1.62 (1.45, 1.81)* | 2.10 (1.77, 2.49)* |
| Atrial fibrillation | 1.00 (0.82, 1.22) | 1.16 (1.09, 1.23)* | 1.20 (1.04, 1.40)** | 1.22 (1.03, 1.46)** | 1.28 (1.04, 1.58)** | 1.36 (0.96, 1.93) |
| Ischaemic stroke | 1.52 (1.08, 2.13)** | 1.50 (1.41, 1.61)* | 1.52 (1.28, 1.79)* | 1.36 (1.07, 1.72)** | 1.38 (1.09, 1.74)** | 2.16 (1.47, 3.17)* |
| Hemorrhagic stroke | 3.26 (1.20, 8.85)** | 2.56 (2.12, 3.10)* | 1.46 (0.80, 2.66) | 2.00 (0.99, 4.05) | 5.40 (2.87, 10.1)* | 7.85 (1.91, 32.3)** |
| Transient ischaemic attack | 0.74 (0.18, 2.97) | 0.81 (0.67, 0.98)** | 1.18 (0.68, 2.04) | 1.04 (0.49, 2.19) | 0.98 (0.60, 1.61) | 0.60 (0.19, 1.88) |
| Chronic kidney disease | 2.51 (1.94, 3.25)* | 2.90 (2.67, 3.16)* | 2.68 (2.24, 3.22)* | 3.09 (2.40, 3.96)* | 3.03 (2.23, 4.12)* | 2.62 (1.65, 4.15)* |
| Malignant neoplasm | 2.33 (1.64, 3.31)* | 2.42 (2.25, 2.59)* | 2.43 (1.95, 3.04)* | 2.24 (1.69, 2.97)* | 1.88 (1.46, 2.43)* | 1.02 (0.68, 1.54) |
Discussion
Our findings revealed that older age, male sex, lower income level, diabetes, myocardial infarction, atrial fibrillation, chronic kidney disease or malignant neoplasm were associated to an increased risk of death from AVD. Particularly noteworthy, AS, ASAR, and RAS exhibited similar 10 year SR while AR, RAR and RASAR demonstrated higher rates compared with AS, ASAR, and RAS. AR accounted for the highest proportion among all AVD types. The age-standardized incidence of non-rheumatic AVD remained consistent from 2006 through 2017, whereas the age-standardized prevalence of non-rheumatic AVD increased over the same period.
Death risk and 10-year SRs
Our study revealed that the risk of death for AVD increased with older age, male sex, those with lower income levels, and the presence of comorbidities such as diabetes, myocardial infarction, atrial fibrillation, chronic kidney disease or malignant neoplasm. These findings are consistent with previous retrospective population-level epidemiological study on hospitalized care in Scotland involving 19 733 adult patients with non-congenital AVD.11 Additionally, prior studies have found association between AS and hypertension and high cholesterol.12, 13 Interestingly, our analysis showed that AVD patients with hypertension or dyslipidaemia had a lower HR. This observation might be due to more frequent medical treatment in these patients rather than the actual comorbidities themselves. However, due to constraints in the KNHIS data, we were unable to analyse the specific distribution of anti-hypertensive medication and lipid-lowering agents. Nonetheless, our study found that over 70% of AVD patients were aged 60 years or older, highlighting the age-related burden of cardiovascular risk factors in this population. In particular, the HR for ASAR and RAS in older age was higher than for other AVD. According to the 2019 Korea National Health and Nutrition Examination Survey, risk factors for cardiovascular disease such as hypertension and hypercholesterolemia have increased in both sexes after the age of 60s. In chronic disease management, treatment-based control rate (control rate) for hypertension was between 60% and 70%, while dyslipidaemia showed a control rate of more than 80%.14 Since the KNHIS data only displays medications in the benefit category, we cannot determine which specific treatments for hypertension or dyslipidaemia were used. Additionally, the leading causes of death among AVD patients were diseases of the circulatory system and malignant neoplasm, aligning with Korea's overall top causes of death.15 Our analysis showed that a significant number of deaths among AVD patients were due to malignant neoplasms, as reflected in the KNHIS dataset. While we acknowledge the suggestion to exclude malignant melanoma and prostate neoplasms due to their differing prognosis, the available data categorized causes only due to the first digit following the capital letter in ICD-10 coding. This limitation prevented us from excluding these specific malignancies. However, the detailed distribution of deaths due to malignant neoplasms (C4X and C6X categories) has been provided to offer a clear understanding of the cause of death among AVD patterns.
Despite the evolution of both surgical aortic valve replacement and transcatheter aortic valve implantation (TAVI) procedures in recent years, our analysis faced limitations in adjusting for the calendar year due to the absence of comprehensive TAVI data in the KNHIS dataset. TAVI procedures, being outside the coverage of KNHIS, are not reflected in the national database, preventing a full adjustment for calendar year effects. However, the Main Surgery Statistical Yearbook from 2010 to 201716 provides insight into the increasing trend of non-rheumatic aortic valve surgeries, indicating a rise in surgical interventions over the years. This information helps contextualize the evolving landscape of aortic valve treatments in Korea.
Regarding the 10 year SR, AS, ASAR and RAS showed similar patterns of approximately 50%. In contrast, AR, RAR and RASAR showed higher 10 year SRs compared with AS, ASAR and RAS. The distribution of death by age group and AVD types is shown in Table S1-2. In our study, the proportion of patients aged 80 years and older was 24%–28% for AS, ASAR and RAS and 15%–19% for AR, RAR and RASAR. The proportion of deaths in those aged 80 years and older was 42%–48% for AS, ASAR and RAS and 35%–41% for AR, RAR and RASAR. AS, ASAR and RAS have a higher proportion of individuals over 80 years old and a higher death proportion compared with AR, RAR and RASAR. Therefore, we think that the lower SR for AS compared with AR is attributable to the older age of individuals with individuals with AS, ASAR and RAS, as well as the higher distribution of death in these groups.
For age-adjusted survival curves, we acknowledge the importance of age adjustment in survival analyses. In Figure 2, we have provided age-adjusted survival curves, presenting survival outcomes by sex and age group for various types of AVD such as AS, AR, ASAR, RAS, RAR and RASAR. This detailed analysis highlights the impact of age on SR, offering a comprehensive understanding of how survival outcomes vary across different patient demographics. By adjusting for age in these analyses, we aim to provide a more accurate representation of survival outcomes, accounting for the significant influence of age on mortality rates in patients with AVD. These findings provide valuable insights into the distribution, incidence, prevalence and death risks associated with different types of AVD. Understanding these factors is crucial for developing targeted prevention and management strategies for AVD patients.
Distribution, incidence and prevalence
In our study, the distribution of AR was the most among all AVD. This finding contrasts with some prior studies, such as retrospective population-level epidemiological study in Scotland (1997–2005) and a Swedish nationwide register study (2003–2010), both of which reported AS as the most common among non-rheumatic AVD.11, 17 However, the male-to-female ratio of overall AVD in our study favoured females, which aligns with the Scotland study but contrasting with a Chinese population-based survey.11, 18 In most AS studies, the distribution of male in AS was larger.19, 20 However, The CANHEART Aortic Stenosis Study, part of the CANHEART (Cardiovascular Health in Ambulatory Care Research Team) ‘big data’ initiative, showed a lower male distribution in AS compared with females.13 Data from KNHIS between 2006 and 2011 showed that males were less represented in both non-rheumatic and rheumatic aortic valve disorders compared with females.1 Our study also found that 70% of all AVD patients, including non-rheumatic and rheumatic AVD, were 60 years or older, consistent with previous studies that have shown a higher proportion of AVD older individuals.21, 22 This study highlights the higher incidence of rheumatic AS compared with degenerative AS. Unfortunately, there are few studies comparing the incidence of rheumatic AS versus non-rheumatic AS using large national databases.
The age-standardized incidence of non-rheumatic AVD remained stable from 2006 through 2017, while the age-standardized prevalence of non-rheumatic AVD increased during the same period. This pattern is similar to Swedish National data, which also demonstrated increasing prevalence in AS overtime.20 The stable incidence and increasing prevalence of AVD in Korea can be attributed to its ageing population.2 Conversely, the age-standardized incidence and prevalence of rheumatic AVD decreased during the study period. The factors determining chronic RHD from ARF are not yet fully established but are likely related to repeated episodes of often subclinical secondary infections, resulting in progressive valve fibrosis and self-sustaining valve inflammation. Individuals experiencing repeated infections are more progress to chronic RHD. The burden of RHD disproportionately affects low-income countries and socioeconomically disadvantage groups in high-income countries. Globally, the incidence of ARF globally has been challenging to ascertain, with estimates ranging from 10 cases per 100 000 to as high as 374 cases in Pacific and indigenous Australian and New Zealand communities.6, 23 Nonetheless, rheumatic AVD persists, and it is essential to maintain and promote good personal hygiene practices to further reduce its prevalence.
Limitations
Several limitations of the current study must be acknowledged. First, the National Health Insurance Benefit records may have overlooked AVD patients who did not utilize medical services or who self-funded their medical expenses. Consequently, the incidence, prevalence, SR and death risk of AVD in this study may have been underestimated or overestimated. Second, the large 95% CIs for RAS in individuals aged 80 years or older suggest statistical uncertainty for these results. Third, the inherent constraints of the KNHIS database prevented the assessment of clinical parameters, such as echocardiography, electrocardiography or cardiac magnetic resonance imaging, which are essential for determining the severity or cause of AVD, particularly the cause of AS in children. Therefore, the severity grades or cause for AS and AR not recorded in the database limit our ability to analyse the impact of disease severity on outcomes. Fourth, the diagnoses and cause of death are based on ICD-10 codes, which introduces a risk of bias concerning diagnosis. Fifth, the lack of comprehensive TAVI data in the KNHIS dataset limited our ability to adjust for the calendar year in analysing the outcomes of surgical or transcatheter aortic valve replacement. Sixth, the use of anti-hypertensive medication or lipid-lowering agents was limited due to the available data. Seventh, the adjusted HR for AS or AR did not account for aortic dissection.
Conclusions
This study observed an elevated risk of death associated with AVD in individuals of older age, male sex, lower income levels, those with heart failure and chronic kidney disease. Notably, over 70% of AVD patients were aged 60 years or older. The 10 year SR for AS, ASAR and RAS exhibited a consistent pattern, approximately 50%. Over the course of a decade, the age-standardized prevalence of non-rheumatic AVD displayed an increasing pattern, while the age-standardized incidence and prevalence of rheumatic AVD declined. Among AVD patients, disease of the circulatory system and malignant neoplasms were the primary causes of death. These patterns imply that AVD can be regarded a degenerative disease with age-dependent effects. Our findings should be taken into consideration when designing future research studies and healthcare policies aimed at addressing the needs of AVD patients.
Acknowledgements
This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Republic of Korea (HI22C0154). And this study used data from the National Health Insurance Service (Research management number NHIS-2019-1-147), but the study results are not related to the National Health Insurance Service.
Conflict of interest
None declared.
Funding
This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Republic of Korea (HI22C0154).
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Abstract
Aims
Few studies have examined the incidence, prevalence, survival rate and death risk for non‐rheumatic and rheumatic aortic stenosis (AS; RAS), aortic insufficiency (AR; RAR) and aortic stenosis with insufficiency (ASAR; RASAR). This study aims to identify the epidemiology of AS, AR, ASAR, RAS, RAR and RASAR.
Methods and results
Data were collected from newly diagnosed non‐rheumatic and rheumatic aortic valve disorders (AVD, ICD‐10: I35 and I06, n = 101 895, female: male = 6:4) including AS, AR, ASAR, RAS, RAR and RASAR, excluding congenital heart disease. The data were sourced from the National Health Insurance Service in Korea from 2006 through 2017. Among all AVD, AR had the highest distribution. More than 70% of AVD patients were age ≥ 60 years. The age‐standardized incidence of non‐rheumatic AVD remained stable over the decade while the age‐standardized prevalence increased. Conversely, both the incidence and prevalence of rheumatic AVD decreased. The 10 year survival rates (SR) of AS (49.2%), ASAR (50.2%) and RAS (51.4%) were lower than those for AR (64.5%) and RAR (69.2%). The adjusted hazard ratio for AVD was higher in individuals who were older, male, had a lower income level, diabetes mellitus, myocardial infarction, heart failure, atrial fibrillation, stroke, chronic kidney disease or malignant neoplasms.
Conclusions
Over 70% of AVD patients were age ≥ 60 years. The 10 year SR of AS, ASAR and RAS exhibited similar patterns, all of which were lower than the SR for other AVD. AVD portends a worse prognosis in older individuals, males, those with lower income levels and those with comorbidities.
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Details
; Kim, Eun Kyoung 1 ; Park, Seung Woo 1 1 Division of Cardiology, Department of Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea