7-year Follow-up Research Articles

Mediterranean-type diet trajectories and 20-year cardiovascular disease incidence: the ATTICA study (2002-2022)

Abstract Background/Introduction The protective effects of the Mediterranean-type diet (MTD) against cardiovascular disease (CVD) are well-known. However, based on a recent systematic review of 57 studies with 1,125,560 participants, MTD adherence has declined worldwide, even in the Mediterranean region, compared to the past, especially in the last decade. Moreover, studies evaluating changes in diet and CVD risk are scarce. Purpose The aim of this study was to longitudinally evaluate MTD adherence and changes in MTD adherence during 20-years of follow-up and its relation to 20-year CVD incidence. Methods Participants initially free-of-CVD from the ATTICA study were used (n=1,986). At 2002 and 2022, CVD events were assessed according to WHO-ICD-10 and MTD adherence was assessed via MedDietScore (range: 0-55). Hence, MTD trajectories were defined according to MTD adherence in 2002 and in 2022 as: low-low, low-high, high-low, high-high (i.e., high: MedDietScore >27/55). Results During the 20-year follow-up, 30.2% (n=600) of the participants were always away (i.e., low-low), 30.0% (n=596) went away (high-low), 21.4% (n=424) were always close (high-high) and 22% got closer (low-high) to the MTD. The 20-year CVD incidence was: 38.8% (n=233), 87.7% (n=321), 10.2% (n=61) and 24.3% (n=103) in those in the low-low, low-high, high-low and high-high trajectory, respectively (p-value<0.001). In multi-adjusted models, adjusted for socio-economic, clinical and lifestyle parameters, it was found that compared to those who were always away from the MTD, those who were always close had 68% lower CVD risk [Hazard Ratio-HR: 0.32, 95%Confidence Interval-CI: 0.14, 0.72], while those who went away during the 20-year follow-up had 47% lower CVD risk [HR: 0.53, 95%CI: 0.32, 0.86]. Conclusion Our study findings highlight the long-lasting effects of the MTD adherence early in the life-course. Public health measures to prevent CVD should focus on facilitating MTD adherence, as early in life as possible.

Idiopathic pulmonary arterial hypertension, associated with connective tissue disease and comorbidities: prognostic differences? Results the Spanish Registry of pulmonary hypertension (REHAP Registry)

Abstract Introduction Idiopathic pulmonary arterial hypertension (iPAH) and associated with connective tissue disease (PAH-SSc) are the most frequent groups of pulmonary arterial hypertension (PAH) but their long-term survival is usually unequal. Comorbidities, increasing in frequency in these patients, show prognostic influences but it is not known whether these differ in both groups of patients. Methods We collected patients diagnosed with iPAH, heritable, associated with drug or toxine exposure and PAH-SSc between 2014 and 2023 from the Spanish Registry of Pulmonary Hypertension. Patients are classifies into iPAH and PAH-SSc. We analyzed baseline characteristics and the distribution of the different comorbidities in the two groups. Survival analyses estimated by Kaplan-Meier analysis using the log-rank test were done according to PAH etiology and comorbidities and Cox proportional hazard analyses were performed to determine the effects of baseline characteristics on survival. Results Seven hundred and fifty-seven patients were selected for this study. The characteristics of the patients are shown in Table 1. Patients with PAH-SSc compared to iPAH were older (62 vs 56 years), more female (81.8% vs 62.4%), had a more favorable hemodynamic profile, TAPSE/sPAP ratio and lower NT-proBNP levels. No differences were found in functional class or 6MWT. We found a higher proportion of patients in a low and intermediate risk profile, according to ESC, in patients with PAH-SSC as opposed to PAHi (46.8/50.9% vs. 29.3/64.5%; p<0.001). Regarding comorbidities, history of smoking (27.1 vs 54%; p<0-001), obesity (17.1 vs 20.7%; p<0.001) and diabetes (9.4 vs 22.1%; p<0.001) are less frequent in PAH-SSc than in iPAH. There are no differences in the rest of the comorbidities studied in the two groups of patients. In a survival analysis, we found no differences between patients with iPAH and PAH-SSc at 7-year follow-up. Patients with ≥ 3 comorbidities had statistically significantly higher mortality (p<0.001) compared to those with 0 or 1-2 comorbidities in both etiologies. There were no differences between 0 and 1-2 comorbidities. (Figure 1). Variables associated with mortality were male sex (HR 1.9, 95% CI 1,28 – 2.8), age (HR 1.04, 95% CI 1.02 – 1.06), the intermediate risk profile (HR 2.64, 95% CI 1.62 – 4.32) and high risk profile (HR 9.97, 95% CI 4.36 – 18.47), but not etiology. The presence of connective tissue diseases, were not associated with increased mortality. Conclusions Patients with PAH-SSc show lower comorbidities, better hemodynamic profile, RV-PA coupling and risk profile than those with iPAH. Comorbidity has a great relevance in survival but without differences according to etiology. The presence of male sex, age, the intermediate and high risk profile is associated with worse survival, but not the connective tissue diseases.

The importance of comorbidities in idiopathic and associated with connective tissue disease pulmonary arterial hypertension: from the Spanish Registry of Pulmonary Hypertension (REHAP Registry)

Abstract Introduction Comorbidities play a major role in the prognosis of patients with pulmonary arterial hypertension (PAH). These comorbidities are present in more than 80% of patients diagnosed in the last years with idiopathic PAH (iPAH) and their presence is associated with increased morbidity and mortality although its influence on PAH associated with connective tissue disease (PAH-SSc) is unknown. We studied the impact of comorbidities on iPAH and PAH-SSc in the Spanish population. Methods We collected patients diagnosed with iPAH, heritable, associated with drug or toxine exposure and PAH-SSc between 2014 and 2023 from the Spanish Registry of Pulmonary Hypertension. Patients are classified into: no comorbidities, 1-2 comorbidities and ≥3 comorbidities. We analyzed the impact of comorbidities in baseline characteristics, exercise capacity and hemodynamic profile, as well as in the risk profile and initial treatment. Survival analyses estimated by Kaplan-Meier analysis using the log-rank test and Cox proportional hazard analyses were performed to determine the effects of baseline characteristics on survival. Results 757 patients were selected for this study. The characteristics of the patients are shown in Table 1. As the number of comorbidities increases (0/1-2/≥3) we found higher age (49/59/67 years; p<0.001), higher percentage of male sex (12.9/29.9/43.4%; p<0.001) and higher FC III at diagnosis (42.7/46.9/59.6%; p=0.013). We observed a shorter distance in 6MWD, higher NT-proBNP levels, lower DLCO and a less unfavorable hemodynamic profile (PAPm, PAWP, CI and PVR). The most frequent comorbidities were a history of smoking (46.4%), followed by arterial hypertension (41.5%), obesity (24.6%) and chronic kidney disease (19.2%). Diabetes mellitus, although less frequent, reached more than 55% in patients with ≥3 comorbidities (p<0.001). The presence of ≥ 3 comorbidities was more frequent in iPAH than PAH-SSc (p<0,001). Intermediate risk profile was the most common (58.4%) and this reached 68.7% in those with ≥3 comorbidities due to a lower number of patients in a low-risk profile (p<0.001). A statistically significant lower survival (p<0.001) was observed in patients with ≥ 3 comorbidities; however, we found no differences between 0 and 1-2 comorbidities at 7-year follow-up (Figure 1). Variables associated with mortality were male sex (HR 1.88, 95% CI 1,26 – 2.8), age (HR 1.04, 95% CI 1.02 – 1.06) and the presence of ≥3 comorbidities (HR 1.49, 95% CI 0.98 – 2.27), not the presence of connective tissue diseases, which were not associated with increased mortality in our study. Conclusions The presence of comorbidities in iPAH and PAH-SSc is very frequent in the Spanish population. They are associated with a worse clinical profile, risk profile, lower use of oral double theraphy and prostacyclins. The presence of ≥3 comorbidities is associated with worse survival, not the presence of 1-2 comorbidities or connective tissue disease.

Female Reproductive System and Thyroid Dysfunction: Findings from a 12-Year Follow-Up in the Tehran Thyroid Study.

Background: The impact of thyroid dysfunction (TD) on the female reproductive system has been extensively documented. While there is evidence suggesting that alteration in female reproductive status may affect thyroid function, conflicting results have prevented definitive conclusions. This study aimed to investigate the associations of parity, spontaneous abortion (mentioned as abortion throughout this study), and menopause status with the prevalence and incidence of TD. Methods: From the Tehran thyroid study population, 2711 participants were included in the cross-sectional analysis to explore associations between female reproductive status and TD. Overall, 2191 participants with euthyroid were included in the survival study and followed up in 3-year intervals. Multinomial logistic regression was adopted in cross-sectional analysis and multivariable Cox proportional hazard model was used to determine associations between the incidence of TD with parity, abortion, and menopause status, adjusting for age, smoking, body mass index, and thyroid peroxidase antibodies positivity. Results: At the baseline, multiple parities (≥4) were significantly associated with overt hypothyroidism (odds ratio [OR] = 1.12; confidence interval [CI] 1.0-1.26) and subclinical hyperthyroidism (OR = 1.11 [CI 1.03-1.21]). Furthermore, multiple abortions were associated with overt hyperthyroidism (OR = 2.09 [CI 1.02-4.26]). Over the course of the study, multiple parities were significantly associated with the incident subclinical and clinical hypothyroidism. Conversely, a history of abortion was associated with a reduced risk of incident overt hypothyroidism. We found no significant association between menopause status and the prevalence or incidence of either hypothyroidism or hyperthyroidism. Conclusions: Our results suggest that the female reproductive system may be associated with thyroid function. Parity and abortion are associated with the occurrence of TD. A deeper understanding of the underlying mechanisms of the cellular and molecular alterations in signaling cascades during pregnancy is necessary to fully elucidate these associations.

Albumin creatinine index added to the grace score increases its discriminative capacity for mortality at 12 years of follow-up in patients with acute coronary syndrome

Abstract introduction There is currently no information on the prognostic value of the GRACE score with the additional addition of the albumin-creatinine index (ABI) for the prediction of very long-term mortality in unselected populations of acute coronary syndromes (ACS). Objectives To evaluate the additive value of the albumin-creatinine index in spontaneous urine sample to the GRACE score for the prediction of 12-year mortality from all causes in an unselected cohort of patients with acute coronary syndrome. Material and methods A prospective cohort study was carried out, which included patients admitted to a Community Hospital with a diagnosis of ACS. These patients had their IAC measured in a single spontaneous urine sample based on the principle of immunoturbidimetry in the first 24 hours of admission. The end point of the analysis was all-cause mortality at follow-up. The GRACE 2.0 score was calculated for all patients in the study. The scores were compared according to the following metrics: their power to discriminate between events and non-events (ROC Areas), calibration or goodness of fit, evaluating the agreement between the proportion of events and non-events expected by both scores observed by Hosmer Lemeshow Test. The comparison between the areas under the ROC Curves was carried out using De Long's test with the MEDCALC program version 19.1.7. The net reclassification index and its 95% CI (GRACE score + IAC/GRACE score) were evaluated. Results 600 patients with ACS were analyzed, with an average age of 64 years. The GRACE score risk subgroups were divided by the established cut-off values: low risk (0 to 108), intermediate (109 to 139) and high risk (greater than 139). The area under the curve of the Grace score for mortality during follow-up was 0.79 (95% CI 0.69-0.89), while the area under the ROC curve of the GRACE + IAC score was 0.81 (95% CI 0.74-0.87). ). Comparing the two areas by the De Long test, the difference was statistically significant (P < 0.0001; 95% CI 0.07- 0.015). On the other hand, contingency tables were developed and the Hosmer Lemeshow Test (goodness of fit) was performed on the GRACE score and the GRACE + IAC score, observing agreement between expected events and non-events, throughout all subgroups of risk. In addition, reclassifications were made into deceased and survivors by applying the GRACE + IAC score on the GRACE score. The net reclassification rate was 28% (95% CI 21-35). The chi square of its Mc Nemar Test was 3.69 p < 0.0002. The absolute comprehensive discriminatory improvement was 0.01 (95% CI 0.009-0.02) and the corresponding relative value was 8.2% (95% CI 7.9-8.5). Conclusions In this unselected ACS cohort, the albumin-creatinine index added to the GRACE score significantly increases its ability to discriminate mortality from all causes in a 12-year follow-up.Comparison between ROC curvesHosmer Lemeshow test

Mean body mass index during 20 years of follow-up and cardiovascular disease incidence: results from the ATTICA cohort study (2002-2022)

Abstract Background/Introduction The Global Burden of Disease study has estimated that the burden of increased body mass index (BMI) (i.e., approximately >2.000.000 deaths and >70.000.000 disability-adjusted life years) was predominantly dominated by cardiovascular disease (CVD) during 1990–2017. However, the lifelong body weight (BW) status and its relation to CVD risk remains poorly elucidated. Purpose The purpose of this study was to evaluate the relationship between mean BMI during a 20-year period and CVD incidence. Methods Participants initially free-of-CVD from the ATTICA cohort study were used (n=1,348). At baseline and the 10- and 20-year follow-up, CVD events were assessed, according to WHO-ICD-10. Based on three measurements of weight and height, BMI for each measurement was calculated, and, afterwards, the mean BMI during the whole 20-year period was computed. Results During the whole 20-year period, 41% (n=552) of participants consistently had a normal BW, 48% (n=651) had overweight and 11% (n=145) had obesity. The 20-year CVD incidence was: 8.0% (n=44), 14.9% (n=97) and 19.3% (n=28) in those who consistently had a normal BW, overweight and obesity, respectively (p-value<0.001). In multi-adjusted Cox proportional hazards models, adjusted for age, sex, clinical and lifestyle characteristics, compared to participants who consistently had a normal BW, those who had overweight as well as those who had obesity had almost 2 times higher risk to develop CVD during the 20-year period [Hazard Ratio-HR: 1.73, 95%Confidence Interval-CI: 1.13-2.66 and HR: 2.04, 95%CI: 1.11-3.76, for participants with overweight and obesity, respectively]. Conclusion The study findings highlight that, despite the observations of the J-shaped relationship between BMI and all-cause mortality observed in some studies, both overweight and obesity can be significant risk factors for CVD, when lifelong BW status is assessed. Therefore, currently, new lifelong measures are needed to prevent and manage the pervasive overweight and obesity.

Circadian heart rate fluctuations predict 21-year cardiovascular and all-cause mortality in type 2 and type 1 diabetes

Abstract Background Alterations in circadian heart rate (HR) fluctuations have been associated with cardiovascular events in the general population. This study aimed at defining their long-term prognostic value for cardiovascular and all-cause mortality in patients with diabetes. Methods We examined a cohort of 349 patients with type 2 or type 1 diabetes (52% women, age 57.1±11.9 years, BMI 29.4±5.9 kg/m2, HbA1c 8.6±2.1%, 81% type 2 diabetes) who underwent 24h ambulatory blood pressure and HR monitoring (ABPM) and assessment of diabetic microvascular complications. The median standard deviation (SD) value of ABPM-derived HR measurements was used to define patients with low daily HR fluctuations (low 24h-HR SD), while a <10% decline in average night-time vs day-time HR identified patients with blunted nocturnal HR dip (n=107, 31%). The clinical features and time-dependent prognostic impact of these conditions were evaluated over a 21-year observational follow-up. Results Low 24h-HR SD and blunted nocturnal HR dip were associated with an adverse cardiometabolic risk profile and high prevalence of cardiac autonomic neuropathy and nephropathy. After 6,251 person-years of follow-up (21.0 [14.0-21.0] years), a total of 136 (39%) deaths occurred, of which 100 (68%) of cardiovascular cause. After adjustment for potential confounders, the low 24h-HR SD group had a higher risk for both cardiovascular (hazard ratio 1.99, 95% CI 1.29–3.06, p=0.002) and all-cause mortality (hazard ratio 1.50, 95% CI 1.03–2.18, p=0.033), compared with high 24h-HR SD. Consistently, patients with blunted nocturnal HR dip had a higher adjusted risk for cardiovascular (1.61, 95% CI 1.07–2.43, p=0.023) and all-cause mortality (1.61, 95% CI 1.11–2.34, p=0.012), compared with those with preserved nocturnal HR dip. Conclusions Impaired circadian HR fluctuations are frequent in patients with long-standing diabetes and are associated with microvascular disease and increased long-term cardiovascular and all-cause mortality. Identifying these conditions via 24h-ABPM may provide a cost-effective risk stratification tool in this high-risk population.Kaplan-Meier curves

Longitudinal associations between accelerometry-assessed sleep clusters and obesity in adolescence and young adulthood: the German GINIplus and LISA birth cohorts study

Abstract Background Some studies have identified diverse sleep patterns in adolescents and adults by considering multidimensional objective sleep parameters. However, whether sleep patterns are consistent from adolescence to young adulthood and their long-term associations with obesity remain unknown. Purpose This study aimed to investigate the longitudinal associations of objectively measured and clustering-identified sleep patterns with body mass index (BMI) and overweight/obesity in adolescence and young adulthood, and to test whether these associations change over time or are modified by genetic risk. Methods A total of 1973 participants wearing 7-day accelerometers in either 15-year (n=1347, aged 14.3-16.4 years) and/or 20-year (n=1262, aged 19.5-22.4 years) follow-ups of German GINIplus and LISA birth cohorts were included. Sleep clusters were identified by K-means cluster analysis on 12 accelerometry-assessed sleep characteristics at each follow-up. BMI and overweight/obesity were measured by physical exams or self-/parent-reported questionnaires. Multivariable linear and logistic regression models with generalized estimating equations were tested. The interaction effects with time of follow-ups and polygenic risk scores (PRS, n=1087) for BMI were further examined. Results Although sleep characteristics changed from adolescence to young adulthood, such as shorter total sleep time (mean 7.2 to 6.6 hours), the consistent five sleep clusters were classified in both periods: good sleep, delayed sleep phase, sleep irregularity and variability, fragmented sleep, and prolonged sleep latency. Compared to the "good sleep" cluster, the "prolonged sleep latency" cluster showed significant associations with higher BMI (β=0.56, 95% confidence interval (CI) = [0.06, 1.05]) and increased odds of overweight/obesity (odds ratio (OR)=1.55, 95%CI= [1.02, 2.34]). PRS was associated with higher BMI (β=0.65, 95%CI= [0.39, 0.91]) and overweight/obesity (OR=1.52, 95%CI= [1.15, 2.00]), with no significant gene-sleep cluster interaction effect. Only among males, the interaction effects with time of follow-ups on overweight/obesity were observed in the "delayed sleep phase", "sleep irregularity and variability", and "fragmented sleep" clusters (p-interaction <0.05), showing more harmful effects with increasing age. Conclusions Five sleep patterns were identified consistently across adolescence and young adulthood, and the "prolonged sleep latency" pattern was associated with higher BMI and overweight/obesity, independent of genetic risk. For young adult males, "delayed sleep phase", "sleep irregularity and variability" and "fragmented sleep" patterns seemed to have more unfavorable impacts on overweight/obesity.

Relationship of serum vitamin D levels with atrial fibrillation incidence: The HUNT Study

Abstract Background Evidence on the association between serum vitamin D levels and incidence of atrial fibrillation (AF) was inconclusive. To elucidate the nature of the association, we studied the relationship between serum 25-hydroxyvitamin D (25(OH)D) levels and AF incidence in the Norwegian Trøndelag Health (HUNT) Study using both conventional observational and Mendelian Randomization (MR) approaches. Methods 3394 adult participants without AF diagnoses were followed up from HUNT3 (2006-2008) to 2021 in a prospective cohort. Average serum 25(OH)D levels over ten years between HUNT2 (1995-1997) and HUNT3 were calculated and categorized into <50 and ≥50 nmol/L as exposure. AF diagnoses were retrieved from hospital registers and validated by medical doctors. Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI). Furthermore, a one-sample MR was conducted among 36,554 adults who participated in both HUNT2 and HUNT3. An externally weighted genetic risk score based on 19 vitamin D-related genetic variants, chosen for their clear biological functions in serum vitamin D transport, synthesis and metabolism, was used as instrument. We applied the Wald ratio method to assess the causal effect. Results During a median 13-year follow-up, 303 AF cases were diagnosed in the prospective cohort. Serum 25(OH)D level <50.0 nmol/L was associated with a 26% reduced incidence of AF (HR 0.74, 95% CI 0.58 to 0.95), compared to serum 25(OH)D ≥50 nmol/L after adjustment for confounders. Genetically determined 10 nmol/L decrease in serum 25(OH)D level was associated with a 7% reduced incidence of AF (HR 0.93, 95% CI 0.86 to 1.00) in the MR analysis. Sensitivity analyses supported this positive association. Conclusions We found a consistent positive association between serum 25(OH)D level and AF incidence in the Norwegian HUNT population using both observational and MR approaches. Key messages • Serum vitamin D levels appeared to be positively associated with the incidence of AF. • Vitamin D supplementation should be prescribed with caution, especially for people at high risk for AF.

Incidence and factors associated with mitral valve reoperation in patients undergoing intervention for mitral regurgitation: a nationwide cohort study

Abstract Background When intervention is needed for the treatment of mitral regurgitation, the risk of reoperation is of concern for both patients and physicians. As such, contemporary and nationwide data on the incidence and factors associated with mitral reoperation can provide crucial information to support patient education and clinical follow-up after intervention. Purpose To examine the incidence of mitral reoperation in patients operated for mitral regurgitation. Second, to assess whether reoperation rates differed according to time since surgery and identify potential factors associated with reoperation. Methods Using Danish nationwide registries, patients undergoing first-time surgery for mitral regurgitation 1996–2021 were identified. Exclusion included first-time surgery due to endocarditis. According to index surgery, the population was categorized into 1) mitral repair; 2) mechanical prosthesis; 3) bioprosthesis. Patients were followed from date of discharge. Cumulative incidence of reoperation was examined using competing risk analysis during a maximum of 20-years follow-up. Crude incidence rates of reoperation were reported from 0-6 months and for overall study period. Multivariate Cox analysis was used to examine factors associated with reoperation. Results We identified 7,063 patients: 4,680 (66.3%) with repair (72% male, median age 66), 1,273 (18.0%) with mechanical prosthesis (52% male, median age 59), and 1,110 (15.7%) with bioprosthesis (57% male, median age 74). Median follow-up was 7.2 years, 10.7 years, and 4.5 years, respectively. At end of follow-up, cumulative incidences were 7.7% for repair, 6.8% for mechanical prostheses, and 7.5% for bioprostheses. Of these, reoperation was preceded by endocarditis in 8.0%, 21.5%, and 30.4% of the respective patient groups. The cumulative incidence function demonstrates that the highest proportion of reoperations occurred within first six months, Figure 1. From 0-6 months following surgery, incidence rates per 100 person-years were 9.1 for repair, 11.7 for mechanical prostheses, and 18.4 for bioprostheses, while this was 8.6, 9.4, and 17.0, respectively for the overall study period. Factors associated with increased rate of reoperation were heart failure (HR=1.80, 95% CI 1.40-2.32), chronic renal failure (HR=1.48, 95% CI 1.11-1.98) and chronic obstructive pulmonary disorder (COPD) (HR=1.34, 95% CI 1.01-1.77), Figure 2. Compared to mitral repair, mechanical prostheses were associated with lower rate of reoperation (HR=0.57, 95% CI 0.42-0.78), while there was no statistically significant difference between repair and bioprostheses (HR=1.10, 95% CI 0.81-1.50). Conclusion In patients operated for mitral regurgitation, cumulative incidences of reoperation with a maximum of 20-year follow-up were 7.7% for repair, 6.8% for mechanical prostheses, and 7.5% for bioprostheses. Comorbidities such as heart failure, renal failure and COPD were associated with increased risk of reoperation.Figure 1Figure 2

Early resilience and epigenetic ageing: Results from the prospective Young Finns Study with a 31-year follow-up.

Evidence is accumulating on the connection of early adversities and harsh family environment with epigenetic ageing. We investigated whether early psychosocial resilience is associated with epigenetic ageing in adulthood. We used the population-based Young Finns data (n = 1593). Early psychosocial resilience was assessed in 1980-1989 across five broad domains: (1) index of psychological strength (self-esteem at home/in general/at school, perceived possibilities to influence at home, internal life control), (2) index of social satisfaction (perceived support from family/friends and life satisfaction), (3) index of leisure time activities (hobbies and physical fitness), (4) index of responsible health behaviors (infrequent smoking or alcohol consumption), and (5) index of school career (school grades and adaptation). Epigenetic ages were calculated for blood samples from 2011, and the analyses were performed with variables describing age deviation (AgeDevHannum, AgeDevHorvath, AgeDevPheno, AgeDevGrim) and DunedinPACE. Covariates included early family environment, polygenic risk scores for schizophrenia and major depression, adulthood education, and adulthood health behaviors. All of the early resilience indexes were associated with lower levels of epigenetic ageing in adulthood, most consistently with AgeDevGrim and DunedinPACE. The associations of psychological strength and social satisfaction, in particular, seemed to be non-linear. In a smaller subsample (n = 289), high early resilience was related to lower AgeDevGrim over a 25-year follow-up in those who had high "baseline" levels of AgeDevGrim. In conclusion, early resilience seems to associate with lower level of epigenetic ageing in adulthood. Our results tentatively suggest that early resilience may increase "equality in epigenetic ageing" in a general population.

Elevated 1-Hour Post Load Glucose as a Predictor for Telomere Attrition: a study based on a Chinese Community population.

1-hour post-load glucose (1h-PG) detects dysglycemia-related disorders more effectively than traditional glycemic parameters. Hyperglycemia accelerates aging, whether 1h-PG outperforms in predicting aging remains unclear. To Compare the effectiveness of 1h-PG with other glycemic parameters in identifying and predicting telomere attrition. We conducted a cross-sectional and longitudinal study based on a Chinese community cohort. Multivariate linear regression and logistic regression were used to analyze the associations between glycemic parameters and telomere length. The area under the receiver operating characteristic (AUROC) curve were used to compare the differentiating and predictive ability. Populations were regrouped by glucose tolerance status and 1h-PG to compare telomere length. Analyses were separately conducted in non-diabetic and diabetic populations. The cross-sectional study included 715 participants. Only 1h-PG was significantly negatively associated with RTL in both non-diabetic (β = -0.106, 95%CI -0.068 to -0.007, P = 0.017) (odds ratio [OR] = 1.151, 95% CI 1.069 to 1.239, P = 0.005) and diabetic (β = -0.222, 95%CI -0.032 to -0.007, P = 0.002) (OR = 1.144, 95% CI 1.041 to 1.258, P = 0.035) populations. The longitudinal study recruited 437 populations and 112 remained in 7-years follow-up. 1h-PG was associated with telomere shortening in the non-diabetic group (β = -0.314, 95%CI -0.276 to -0.032, P = 0.016) (OR = 2.659, 95% CI 1.158 to 6.274, P = 0.021). AUROC analysis showed that 1h-PG outperformed other glycemic parameters in identifying and predicting telomere attrition. Reclassification revealed that normal glucose tolerance and prediabetic individuals with elevated 1h-PG had telomere lengths comparable to prediabetic and diabetic populations, respectively. 1h-PG outperforms other glycemic parameters in predicting telomere attrition and can be a valuable marker for early aging detection.

Associations Between Vision and Hearing Impairment and Cardiovascular Diseases: A Longitudinal Cohort of Middle-Aged and Older Adults in China.

Based on the severity of cardiovascular disease (CVD) and sensory impairment in China and the lack of research on this, the aims of our study were to assess the impact of hearing impairment (HI), visual impairment (VI), and concurrent HI and VI (termed dual sensory impairment) on CVD in elderly people, based on a representative sample of China. We used data from the CHARLS (China Health and Retirement Longitudinal Study) for our survey of 11 332 participants. We calculated hazard ratios (HRs) and 95% 95% CIs for CVD, stroke, and cardiac events by using Cox proportional hazards models. HI and VI status were collected through self-reported questions. During the 7-year follow-up, a total of 2156 participants experienced CVD (including 745 stroke and 1605 cardiac events). Compared with the reference, individuals with VI had higher risk of CVD (HR, 1.24 [95% CI, 1.09-1.40]). Individuals with HI also had higher risk of CVD than those without HI (HR, 1.20 [95% CI, 1.09-1.33]). Compared with participants without VI and HI, individuals with dual sensory impairment had a 1.35-fold increased risk of CVD (HR, 1.35 [95% CI, 1.16-1.57]). In addition, individuals with dual sensory impairment also had increased risk of stroke and cardiac events. Our study shows that HI and VI have a combined effect on the incidence of CVD. Based on the high prevalence of CVD around the world, early detection of sensory disorders and the adoption of appropriate measures may contribute to prevent CVD and reduce the burden of clinical diagnosis and treatment of CVD.

Implant design influences the joint-specific outcome after total knee arthroplasty.

The aims were to assess whether joint-specific outcome after total knee arthroplasty (TKA) was influenced by implant design over a 12-year follow-up period, and whether patient-related factors were associated with loss to follow-up and mortality risk. Long-term follow-up of a randomized controlled trial was undertaken. A total of 212 patients were allocated a Triathlon or a Kinemax TKA. Patients were assessed preoperatively, and one, three, eight, and 12 years postoperatively using the Oxford Knee Score (OKS). Reasons for patient lost to follow-up, mortality, and revision were recorded. A total of 94 patients completed 12-year functional follow-up (62 females, mean age 66 years (43 to 82) at index surgery). There was a clinically significantly greater improvement in the OKS at one year (mean difference (MD) 3.0 (95% CI 0.4 to 5.7); p = 0.027) and three years (MD 4.7 (95% CI 1.9 to 7.5); p = 0.001) for the Triathlon group, but no differences were observed at eight (p = 0.331) or 12 years' (p = 0.181) follow-up. When assessing the OKS in the patients surviving to 12 years, the Triathlon group had a clinically significantly greater improvement in the OKS (marginal mean 3.8 (95% CI 0.2 to 7.4); p = 0.040). Loss to functional follow-up (53%, n = 109/204) was independently associated with older age (p = 0.001). Patient mortality was the major reason (56.4%, n = 62/110) for loss to follow-up. Older age (p < 0.001) and worse preoperative OKS (p = 0.043) were independently associated with increased mortality risk. An age at time of surgery of ≥ 72 years was 75% sensitive and 74% specific for predicting mortality with an area under the curve of 78.1% (95% CI 70.9 to 85.3; p < 0.001). The Triathlon TKA was associated with clinically meaningful greater improvement in knee-specific outcome when compared to the Kinemax TKA. Loss to follow-up at 12 years was a limitation, and studies planning longer-term functional assessment could limit their cohort to patients aged under 72 years.

Menopausal Hormone Therapy and Ovarian and Endometrial Cancers: Long-Term Follow-Up of the Women's Health Initiative Randomized Trials.

Menopausal hormone therapy's influence on ovarian and endometrial cancers remains unsettled. Therefore, we assessed the long-term influence of conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA) and CEE-alone on ovarian and endometrial cancer incidence and mortality in the Women's Health Initiative randomized, placebo-controlled clinical trials. Postmenopausal women, age 50-79 years, were entered on two randomized clinical trials evaluating different menopausal hormone therapy regimens. In 16,608 women with a uterus, 8,506 were randomly assigned to once daily 0.625 mg of CEE plus 2.5 mg once daily of MPA and 8,102 placebo. In 10,739 women with previous hysterectomy, 5,310 were randomly assigned to once daily 0.625 mg of CEE-alone and 5,429 placebo. Intervention was stopped for cause before planned 8.5-year intervention after 5.6 years (CEE plus MPA) and after 7.2 years (CEE-alone). Outcomes include incidence and mortality from ovarian and endometrial cancers and deaths after these cancers. After 20-year follow-up, CEE-alone, versus placebo, significantly increased ovarian cancer incidence (35 cases [0.041%] v 17 [0.020%]; hazard ratio [HR], 2.04 [95% CI, 1.14 to 3.65]; P = .014) and ovarian cancer mortality (P = .006). By contrast, CEE plus MPA, versus placebo, did not increase ovarian cancer incidence (75 cases [0.051%] v 63 [0.045%]; HR, 1.14 [95% CI, 0.82 to 1.59]; P = .44) or ovarian cancer mortality but did significantly lower endometrial cancer incidence (106 cases [0.073%] v 140 [0.10%]; HR, 0.72 [95% CI, 0.56 to 0.92]; P = .01). In randomized clinical trials, CEE-alone increased ovarian cancer incidence and ovarian cancer mortality, while CEE plus MPA did not. By contrast, CEE plus MPA significantly reduced endometrial cancer incidence.

Estrogen Plus Progestin and Colorectal Cancer: Long-Term Findings From the Women's Health Initiative Randomized Clinical Trial.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We report long-term colorectal cancer findings from the Women's Health Initiative trial where 16,608 postmenopausal women with a uterus were randomly assigned to daily conjugated equine estrogen (CEE) 0.625 mg, plus medroxyprogesterone acetate (MPA) 2.5 mg, or placebo. When intervention ended after 5.6 years, although there were 44% fewer colorectal cancers in the intervention group (43 v 72, P = .003), the cancers were more commonly lymph node-positive (59.0% v 29.4%, P = .003). Now after cumulative 24-year follow-up, with 431 colorectal cancers, CEE plus MPA no longer influenced colorectal cancer incidence (215 [0.15, annualized rate %] v 216 [0.15], hazard ratio [HR], 0.95 [95% CI, 0.79 to 1.15]). Although not statistically significant, there were more colorectal cancer deaths with CEE plus MPA (87 [0.049] v 69 [0.041] deaths, HR, 1.20 [95% CI, 0.87 to 1.65], P = .26). Vaginal bleeding (54.1% v 5.2% at 6 months) and breast changes were more frequent in the intervention group. After adjusting for postrandomization vaginal bleeding and breast changes, bowel examinations were significantly delayed in intervention group participants (P = .005), potentially contributing to diagnostic delay. Taken together, the findings suggest no clinically meaningful benefit for about 5 years of CEE plus MPA use on colorectal cancer outcome.

Postmastectomy Breast Reconstruction in Irradiated Patients: A 12-year follow-up of Deep Inferior Epigastric Perforator and Latissimus Dorsi Flap Outcomes

The aim of the current study was to conduct a 12-year follow-up on the authors´ previously evaluated group of irradiated patients who underwent postmastectomy breast reconstruction with deep inferior epigastric perforator (DIEP) and latissimus dorsi (LD)-flaps with implant.The follow-up involved 67% of the patients from the original cohort (17 DIEP and 13 LD). Patient-reported outcome measures (PROMS) were measured using the BREAST-Q, SF-36, a satisfaction form, and Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaires. Aesthetics were evaluated by a board of independent plastic surgeons.The average follow-up time was 12.6 years (DIEP) and 11.8 years (LD). Contralateral symmetry procedures were performed on 15 DIEP and 9 LD patients. Both groups underwent an average of 2.5 reconstructive procedures. The BREAST-Q and satisfaction questionnaires showed no group difference. SF-36 showed no group difference but had significantly higher values in both groups compared to the general population with regard to the physical role limitations (p=0.034 and p=0.004, respectively). The DASH scores showed minimal shoulder function impact in the LD group.Aesthetic evaluations revealed a discrepancy between the opinions of the patients and surgeons, with patients valuing the size (p=0.015) and overall aesthetic (p=0.012) of the reconstructed breast higher in the DIEP group. The weighted kappa analysis showed poor agreement between patients and surgeons. Over time, the patients´ preferences shifted from LD to DIEP flaps, possibly due to the more natural aging process associated with autologous reconstruction. This underscores the importance of long term follow-up studies.

Total Temporomandibular Joint Replacement by Samsid Customized Joint Prosthesis: A Case Report with 16 Years of Follow-Up

AbstractTotal temporomandibular joint replacement (TMJR) is a surgical intervention employed for the management of advanced temporomandibular joint (TMJ) disorders, particularly when autogenous grafts are not recommended. With stainless steel implant of glenoid fossa attempted for the correction of ankylosis in the 1960s, total TMJR—which minimizes foreign body reaction and consists of highly biocompatible materials such as Cr-Co-Mo alloy, titanium, and ultra-high-molecular-weight polyethylene—began to be applied. These alloplastic prostheses are available in both standardized and customized forms, comprising components for the mandibular condyle and glenoid fossa. The present case report presents India's first TMJR in a 12-year-old female patient with TMJ ankylosis. Total TMJR was done in her with India's first customized TMJ prosthesis (Samsid TMJ prosthesis), which was designed and manufactured by the author for the first time in India. This study presents a 16-year follow-up of customized TMJR, addressing TMJ ankylosis. Our research showcases the long-term success of Samsid TMJ prostheses in improving pain, oral function, diet, and overall quality of life. The case report also highlights the potential of Samsid TMJ prostheses as a valuable solution for TMJ patients, emphasizing the importance of tailored solutions for lasting joint function restoration. The results presented indicate that the Samsid patient-fitted total TMJR system remains a secure, efficient, and dependable long-term treatment option for the particular patient demographic examined in this research.

Risk factors for intracerebral hemorrhage by five specific bleeding sites: Japan Public Health Center-based Prospective Study.

Evaluating the risk factors for intracerebral hemorrhage is indispensable for primary prevention. However, the pathogenesis varies depending on the bleeding site, and few prospective studies have explored risk factors in detail for each site. The Japan Public Health Center-based Prospective Study is a prospective study comprising a population-based sample of Japanese adults in 1990 (Cohort I) and in 1993 (Cohort II). A total of 34,137 participants (11,907 men and 22,230 women) were enrolled in this study and followed up until 2009 for Cohort I and until 2012 for Cohort II. The association between risk factors (age, sex, blood pressure, serum cholesterol, triglycerides, blood glucose, body mass index, smoking, and drinking status) and intracerebral hemorrhage by its bleeding site (lobes, putamen, thalamus, cerebellum, and brainstem) was assessed using Cox proportional hazards analysis. During a median 20-year follow-up, 571 intracerebral hemorrhage events occurred. Hypertension was associated with an increased risk of total intracerebral hemorrhage, but not lobar hemorrhage. The multivariable hazard ratio (95% confidence intervals) was 2.09 (1.75-2.50) for total intracerebral hemorrhage. In contrast, a low serum total cholesterol level was associated only with lobar hemorrhage (1.73 (1.01-2.96)). Heavy drinking was associated with the risk of total and putamen hemorrhage, and obesity was associated with the risk of putamen hemorrhage. The present study identified different risk factors depending on the bleeding site of intracerebral hemorrhage.

Oral Health Status at Age 60 and 72 Years-A Longitudinal Study.

This study investigated oral health status in 60-year-old individuals over 12 years. Data were obtained from The Swedish National Study on Aging and Care (SNAC). One hundred nineteen 60-year-old individuals (48% females) underwent a clinical and radiographic baseline examination (2001-2003) and follow-up examination in 2013-2015. For statistical analyses, paired t-tests and McNemar's test were performed. Statistical significance was determined at p < 0.05. At the 12-year follow-up, the mean number of teeth and the proportion of individuals having ≥ 20 teeth decreased (p < 0.001). The mean number of teeth with buccal/lingual and approximal caries lesions increased (p < 0.029 and p < 0.031). Individuals with a distance from the cement-enamel junction to the bone of ≥ 5 mm increased in total (p < 0.002) and in males (p < 0.006). The prevalence of gingivitis increased in total (p < 0.001). The prevalence of periodontitis showed a significant increase in total (p < 0.043) and in females (p < 0.039). The present study indicates that oral health status in 60-year-old individuals deteriorates over 12 years. However, the deteriorations were minor in terms of tooth loss, caries lesions, and changes in periodontal status.