The impact of traditional cardiovascular risk factor control on 7-year follow-up atherosclerosis progression in systemic lupus erythematosus.

OBJECTIVES: The 2022 EULAR recommendations for cardiovascular risk management in patients with rheumatic disorders, including SLE, call for rigorous management of cardiovascular risk factors (CVRF). The impact of CVRF target attainment on atherosclerotic plaque progression hasn't been previously evaluated in prospective ultrasound studies. METHODS: A total of 115 patients with SLE and 1:1 age and sex-matched healthy controls who had a baseline carotid and femoral ultrasound examination in our cardiovascular research unit were invited for a 7-year follow-up assessment of new plaque development. We aimed to compare the incidence of plaque progression between SLE patients and controls and reveal the extent to which it is affected by the attainment of European Society of Cardiology (ESC) targets for modifiable CVRFs (blood pressure, smoking status, body weight, lipids and physical activity), and disease-related features (disease duration, disease activity, autoantibodies, treatments). RESULTS: Eighty-six SLE patients and 42 controls had a 7-year follow-up carotid and femoral plaque examination. New plaque development was observed in 32/86 patients vs 8/42 controls (P = 0.037). Patients with SLE had a 4-fold higher risk for plaque progression than controls (OR: 4.16, CI: 1.22, 14.19, P = 0.023), adjusting for potential confounders. Multivariate regression analyses showed a 50% decrease in plaque progression for every modifiable CVRF fulfilling ESC targets (OR: 0.56, CI: 0.34, 0.93, P = 0.026). CONCLUSION: Patients with SLE develop a rapid progression of atherosclerotic plaques which may be drastically reduced by CVRF target attainment according to ESC guidelines.

Outcomes of COVID-19 re-infections: a single-center cohort of 167 patients with systemic rheumatic diseases.

Data on COVID-19 re-infections in patients with systemic rheumatic diseases (SRDs) are lacking. We aimed to describe the course and outcomes of COVID-19 re-infections in these patients versus controls. In this single-center retrospective study, we included 167 consecutive SRD patients with at least one COVID-19 re-infection (mean age 47.3 years, females 70.7%). SRD patients were compared in terms of patient-perceived COVID-19 re-infection severity and hospitalizations/deaths with 167 age/sex-matched non-SRD controls. Logistic regression analysis was performed to assess potential milder re-infection versus primary infection severity, adjusting for study group, demographics (age, sex), vaccination status, body mass index, smoking, and comorbidities. 23 and 7 out of 167 re-infected SRD patients experienced two and three re-infections, respectively, which were comparable to the re-infection rates in controls (two: 32; and three: 2) who also had comparable COVID-19 vaccination history (89% and 95% vaccinated, respectively). In the initial infection, patients with SRDs were hospitalized (7.2% versus 1.8%, p = 0.017), and had received antiviral treatment (16.1% versus 4.7%, p < 0.001) more frequently than controls. However, hospitalizations (1.8% vs 0.6%) and antiviral treatment (7.8% vs 3.5%) did not differ (p > 0.05) between patients and controls at the first re-infection, as well as during the second and third re-infection; no deaths were recorded. Perceived severity of re-infections was also comparable between patients and controls (p = 0.847) and among those on biologic DMARDs or not (p = 0.482). In multivariable analysis, neither SRDs presence nor demographics or comorbidities were associated with COVID-19 re-infection severity. COVID-19 re-infection severity (patient-perceived/hospitalizations/deaths) did not differ between SRDs and controls.

Meta-analysis of placebo-arm dropouts in osteoporosis randomized-controlled trials and implications for nocebo-associated discontinuation of anti-osteoporotic drugs in clinical practice.

Dropout from placebo arms in randomized-controlled trials is a surrogate for nocebo responses, resulting from patients' negative expectations to treatment. Among 16,460 placebo-treated patients in oral anti-osteoporotic drug trials, nocebo dropouts were 8% on average, being higher in older patients. This implies that nocebo may contribute to the osteoporosis treatment gap in clinical practice. PURPOSE: Osteoporosis is a common disease requiring long-term treatment. Despite the availability of effective anti-osteoporotic drugs, adherence to treatment is low. Nocebo, a behavior mostly related to the negative expectations to a certain treatment, decreases adherence and negatively affects treatment outcomes and health-related care costs in chronic diseases. Since in double-blind placebo-controlled randomized trials any unfavorable outcome leading to discontinuation in placebo arms is considered as nocebo, we aimed to investigate the size of nocebo response in patients participating in osteoporosis trials. METHODS: We searched MEDLINE, EMBASE, SCOPUS, and Cochrane databases for dropouts due to reported adverse events in the placebo arms (nocebo dropouts) in all double-blind trials investigating anti-osteoporotic drugs published between January 1993 and March 2022. Only data on bisphosphonates and selective estrogen receptor modulators (SERMs) were analyzed (Prospero registration number CRD42020212843). RESULTS: Data from 44 trials were extracted. In 16,460 placebo-treated patients, the pooled nocebo-dropout was 8% both for bisphosphonates (average: 0.08; range 0.01-0.27; 95%CI 0.06-0.10) and SERMs (average: 0.08; range 0.03-0.15; 95%CI 0.05-0.13). Nocebo-dropouts were higher in bisphosphonate trials enrolling individuals ≥ 65 years (11%) (n = 18) compared to trials enrolling younger individuals (6%) (n = 18) (average: 0.11; 95%CI 0.08-0.13 vs. average: 0.06; 95%CI 0.05-0.08, respectively, p = 0.001). Participants' sex, dosing-intervals, publication year, or severity of osteoporosis had no impact on the nocebo-dropouts. CONCLUSION: Almost 1 in 10 osteoporosis patients receiving placebo in trials of bisphosphonates and SERMs experiences AEs leading to dropout, implying that nocebo contributes to treatment-discontinuation in clinical practice. Efforts to identify and minimize nocebo, especially in older patients, are warranted.

Inappropriate prescribing in geriatric rural primary care: impact on adverse outcomes and relevant risk factors in a prospective observational cohort study.

BACKGROUND: Several tools have revealed an association between potentially inappropriate medications (PIM) and adverse outcomes, but the one most fitted for the rural population has not been determined. AIMS: We investigated the performance of the Screening Tool of Older Persons' Prescriptions (STOPP) and Screening Tool to Alert doctors to the Right Treatment (START) in identifying inappropriate prescribing and its association with adverse outcomes among older rural primary health care users. METHODS: A cohort of consenting outpatients aged ≥ 65 years in a rural Greek primary care center was assessed for PIM and potential prescribing omissions (PPO) using the START/STOPP version 2 criteria. Medications, comorbidities, functional status, and laboratory data were recorded along with 6-month incidence of emergency department visits, hospitalization, and death prospectively. RESULTS: Among 104 participants (median age 78 years, 49.1% women, receiving a median of 6 drugs), PPO was found in 78% and PIMs in 61%. PIM was multivariately correlated with multimorbidity (p = 0.029) and polypharmacy (p < 0,001), while drug-PPO was only associated with multimorbidity (p = 0.039). The number of PIM predicted emergency department visits and hospitalizations at 6-month follow-up (p value 0.011), independent of age, sex, frailty, comorbidities, and total medication number. DISCUSSION: The START/STOPP tool is useful in identifying inappropriate prescribing patterns leading to increased utilization of acute care services in older adults followed at a rural primary care setting. CONCLUSION: Inappropriate prescribing as identified by the START/STOPP criteria is prevalent among older adults with multimorbidity in rural primary care, and independently associated with future acute care visits.

Chronological Age and DNA Damage Accumulation in Blood Mononuclear Cells: A Linear Association in Healthy Humans after 50 Years of Age.

Aging is characterized by the progressive deregulation of homeostatic mechanisms causing the accumulation of macromolecular damage, including DNA damage, progressive decline in organ function and chronic diseases. Since several features of the aging phenotype are closely related to defects in the DNA damage response (DDR) network, we have herein investigated the relationship between chronological age and DDR signals in peripheral blood mononuclear cells (PBMCs) from healthy individuals. DDR-associated parameters, including endogenous DNA damage (single-strand breaks and double-strand breaks (DSBs) measured by the alkaline comet assay (Olive Tail Moment (OTM); DSBs-only by γH2AX immunofluorescence staining), DSBs repair capacity, oxidative stress, and apurinic/apyrimidinic sites were evaluated in PBMCs of 243 individuals aged 18-75 years, free of any major comorbidity. While OTM values showed marginal correlation with age until 50 years (rs = 0.41, p = 0.11), a linear relationship was observed after 50 years (r = 0.95, p < 0.001). Moreover, individuals older than 50 years showed increased endogenous DSBs levels (γH2Ax), higher oxidative stress, augmented apurinic/apyrimidinic sites and decreased DSBs repair capacity than those with age lower than 50 years (all p < 0.001). Results were reproduced when we examined men and women separately. Prospective studies confirming the value of DNA damage accumulation as a biomarker of aging, as well as the presence of a relevant agethreshold, are warranted.

Better outcomes of COVID-19 in vaccinated compared to unvaccinated patients with systemic rheumatic diseases.

OBJECTIVE: Τo report outcomes of breakthrough COVID-19 in comparison with COVID-19 in unvaccinated patients with systemic rheumatic diseases (SRDs). METHODS: Patients with SRD with COVID-19 (vaccinated and unvaccinated) were included by their rheumatologists in a registry operated by the Greek Rheumatology Society in a voluntarily basis. Type, date and doses of SARS-CoV-2 vaccines were recorded, and demographics, type of SRD, concurrent treatment, comorbidities and COVID-19 outcomes (hospitalisation, need for oxygen supplementation and death) were compared between vaccinated and unvaccinated patients. RESULTS: Between 1 March 2020 and 31 August 2021, 195 patients with SRD with COVID-19 were included; 147 unvaccinated and 48 vaccinated with at least one dose of a SARS-CoV-2 vaccine (Pfizer n=38 or AstraZeneca n=10). Among vaccinated patients, 29 developed breakthrough COVID-19 >14 days after the second vaccine dose (fully vaccinated), while 19 between the first and <14 days after the second vaccine dose (partially vaccinated). Despite no differences in demographics, SRD type, treatment or comorbidities between unvaccinated and vaccinated patients, hospitalisation and mortality rates were higher in unvaccinated (29.3% and 4.1%, respectively) compared with partially vaccinated (21% and 0%) or fully vaccinated (10.3% and 0%) patients. CONCLUSIONS: Vaccinated patients with SRD with breakthrough COVID-19 have better outcomes compared with unvaccinated counterparts with similar disease/treatment characteristics.

Atherosclerosis progression in antiphospholipid syndrome is comparable to diabetes mellitus: a 3 year prospective study.

BACKGROUND: Antiphospholipid syndrome (APS) is an autoimmune thrombophilia leading to life-threatening cardiovascular events. Cross-sectional data support that APS is associated with accelerated atherosclerosis, but this has not been confirmed in prospective studies. We aimed to compare the rate of atherosclerosis progression over a 3 year period between patients with APS, diabetes mellitus (DM) and healthy controls (HCs). METHODS: Eighty-six patients with APS [43 with primary APS (PAPS), 43 with SLE-related APS (SLE-APS)] and an equal number of age- and sex-matched patients with DM and HCs who underwent a baseline US of the carotid and femoral arteries were invited for a 3 year follow-up evaluation for atherosclerotic plaque progression. Multivariate analysis was performed for the assessment of determinants of plaque progression after adjustment for disease-related and traditional cardiovascular risk factors. RESULTS: Seventy-four APS patients (74.3% female, 38 with PAPS), 58 DM patients and 73 HCs were included. APS patients exhibited a 3.3-fold higher risk of new atherosclerotic plaque formation compared with HCs (P = 0.031), similar to that in DM [odds ratio (OR) 3.45, P = 0.028]. In APS patients, plaque development risk was higher in SLE-APS vs PAPS (OR 7.75, P = 0.038) and was independently associated with the presence of traditional cardiovascular risk factors as expressed by the Systematic Coronary Risk Evaluation risk (OR 2.31, P = 0.008). CONCLUSION: APS is characterized by accelerated rates of subclinical atherosclerosis to a degree comparable to DM, which is more pronounced in SLE-APS patients. Traditional cardiovascular risk factors are major determinants of this risk, warranting aggressive management as in other disorders with high cardiovascular risk.

Clinical value of amyloid-beta1-40 as a marker of thrombo-inflammation in antiphospholipid syndrome.

OBJECTIVE: Amyloid-beta1-40 (Aß40) is a pro-inflammatory peptide under investigation as a novel biomarker of vascular inflammation, endothelial dysfunction and atherothrombosis in the general population. Herein we tested the hypothesis that Aß40 is deregulated in APS, a systemic autoimmune disease characterized by a thrombo-inflammatory state. METHODS: Between January 2016 and July 2017, we consecutively recruited 80 regularly followed thrombotic APS patients (44 primary, 36 SLE/APS) and 80 age- and sex-matched controls. Plasma Aß40 levels were measured using ELISA and APS-related clinical and laboratory characteristics were recorded. The adjusted Global Anti-Phospholipid Syndrome Score (aGAPSS), a validated risk score in APS, was calculated as a comparator to Aß40 performance to detect arterial thrombotic APS-related events. RESULTS: Higher Aß40 levels were significantly associated with the presence of APS [odds ratio (OR) 1.024 per 1 pg/ml (95% CI 1.007, 1.041)] after adjustment for cardiovascular risk factors (CVRFs), including smoking, arterial hypertension, dyslipidaemia and BMI, and for estimated glomerular filtration rate (eGFR). Among APS patients, increased high-sensitivity CRP (hs-CRP) serum levels was the only independent determinant of Aß40 levels. Importantly, Aß40 levels above the optimal receiver operating characteristics (ROC)-derived cut-off value were independently associated with recurrent arterial events [OR 4.93 (95% CI 1.31, 18.51)] after adjustment for age, sex, CVRFs, hs-CRP and high anti-ß2 glycoprotein I IgG titres. Finally, by ROC curve analysis, Aß40 provided incremental additive value over the aGAPSS by significantly improving its discrimination ability for recurrent arterial thromboses. CONCLUSION: In APS, Aß40 plasma levels are elevated and associated with an adverse thrombo-inflammatory profile. The pathophysiological and prognostic role of Aß40 in APS merits further investigation.

Increased influenza vaccination rates in patients with autoimmune rheumatic diseases during the Covid-19 pandemic: a cross-sectional study.

To assess non-compliance and potential changes in seasonal flu vaccination coverage before and during the Covid-19 pandemic in patients with autoimmune rheumatic diseases (ARDs). Consecutive patients with ARDs followed-up in 2 tertiary hospitals were telephone-interviewed (December 12-30, 2020) regarding seasonal flu vaccination during the 2019/20 and 2020/21 time periods. Self-reported disease flares that occurred after flu vaccination, as well as reasons for non-vaccination were recorded. One thousand fifteen patients were included. The rate of flu vaccination increased from 76% before to 83% during the COVID-19 pandemic (p = 0.0001). The rate of self-reported disease flares was < 1% among vaccinated patients. Reasons for not vaccination in both periods, respectively, included: 'was not recommended by their rheumatologists' (35.0vs.12.2%, p < 0.0001), 'did not feel that they would have any benefit' (36.9 vs. 32.6%), felt unsafe to do so (27.5 vs. 30.2%), or other reasons (18.9 vs. 23.8%). By multivariate analysis, age [OR = 1.03 (95% CI 1.02-1.04)] vs. [1.04 (95% CI 1.02-1.05)] and treatment with biologics [OR = 1.66 (95% CI 1.22-2.24) vs. [1.68 (95% CI 1.19-2.38)] were independent factors associated with vaccination in both periods. These findings, although are temporally encouraging, emphasize the need for continuous campaigns aiming at increasing patients' and physicians' awareness about the benefits of vaccination.

Progression of subclinical atherosclerosis in systemic lupus erythematosus versus rheumatoid arthritis: the impact of low disease activity.

Objectives: The progression of subclinical atherosclerosis in SLE and RA has not been comparatively assessed. We sought to investigate the impact of low disease activity and other disease-related factors on atherosclerosis progression in SLE vs RA. Methods: We performed a 3-year follow-up carotid and femoral artery ultrasound in 101 patients with SLE, 85 with RA and 85 controls after a baseline examination in 115 SLE and 1:1 age- and gender-matched RA patients and controls. We used logistic regression to compare atherosclerosis progression (new plaque development) between SLE and RA vs controls, and assess determinants of progression in SLE patients with different lupus low disease activity state (LLDAS) durations, adjusting for disease-related factors, antihypertensives, antiplatelets, statins and the Systemic Coronary Risk Evaluation 10-year cardiovascular risk. Results: The odds ratio (OR) of plaque progression vs controls was significantly higher in SLE (OR = 2.81, P = 0.043), but not in RA (OR = 2.22, P = 0.109). Results were similar in patients with low disease activity (88% of SLE, 74% of RA). Multivariate determinants of progression in SLE included antiphospholipid antibodies (OR = 2.00, P = 0.043) and Systemic Coronary Risk Evaluation (OR = 2.87, P = 0.019) for all patients, and additionally cumulative corticosteroid dose during follow-up (OR = 1.38, P = 0.013) and disease duration (OR = 1.20, P = 0.022) for patients in LLDAS over entire follow-up. Results were similar for patients with shorter LLDAS durations (>75% or >50% of follow-up). Conclusion: Plaque progression is accelerated in SLE regardless of disease activity, and is associated with antiphospholipid antibodies and the Systemic Coronary Risk Evaluation. In LLDAS, cumulative corticosteroid dose and disease duration are additional determinants of progression.

Increased body weight and central adiposity markers are positively associated with the 20-year incidence of cardiovascular disease: The ATTICA epidemiological study (2002-2022).

Increased adiposity predisposes to cardiovascular disease (CVD). We hypothesized that the presence of obesity would be positively associated with CVD risk, and that the co-presence of central obesity would modify/enhance this association. This was a prospective study (2002-2022) among 1845 Greek adults (mean age, 44.8 ± 13.5 years; men, 49.8%). At baseline, the presence of overweight/obesity was assessed via body mass index (BMI), whereas central obesity was defined as waist circumference ≥102/88 cm, waist-to-hip-ratio ≥0.95/0.80, or waist-to-height-ratio ≥0.50 in men/women. BMI was reevaluated at 10 years and longitudinal BMI trajectories (2002-2012) were identified. CVD incidence was recorded at 20 years (ratio of new cases to the number of participants assessed). Compared with participants with normal weight at baseline, those with obesity exhibited a 27% higher 20-year CVD risk after adjustment for age, sex, lifestyle habits, and medical status (hazard ratio, 1.271; 95% confidence interval, 1.012-1.597). In similar multiadjusted models, compared with participants who were always non-overweight/obese, those who were always overweight/obese exhibited a 40% higher 20-year CVD risk (hazard ratio, 1.403; 95% confidence interval, 1.018-1.936). Additional control for high-sensitivity C-reactive protein attenuated the associations. In the combined baseline body weight classification analysis, CVD incidence was the lowest in participants with normal weight without central obesity, moderate in those with overweight/obesity without central obesity, and highest in those with normal weight and central obesity and overweight/obesity and central obesity (P < .001). Obesity leads to increased CVD risk, partly mediated by inflammation. The combination of BMI with simple measures of abdominal adiposity is superior for CVD risk screening.

Long-Term Adherence to the Mediterranean Diet Reduces 20-Year Diabetes Incidence: The ATTICA Cohort Study (2002-2022).

This study aimed to evaluate the association between adherence to the Mediterranean diet and the 20-year incidence of type II diabetes mellitus (T2DM) among adults from the ATTICA study. This study involved a prospective cohort of 3042 men and women recruited at baseline from the Attica region in Greece. Sociodemographic, anthropometric, lifestyle, and clinical characteristics were evaluated at baseline and follow-up examinations; adherence to the Mediterranean diet was assessed through the MedDietScore (range 0-55); four Mediterranean diet trajectories were identified (i.e., increasing, decreasing, and sustained high and sustained low adherence levels). For the present analysis, data from 2000 individuals with complete information were used (age 43 ± 13 years; 49% men). Over the 20-year period, 26.3% (95%CI 24.4%, 28.3%) of participants developed T2DM; men exhibited a 1.5-times higher incidence compared to women (p < 0.001). Individuals consistently close to the Mediterranean diet throughout the studied period had an improved glycemic and lipidemic profile (at baseline and at 10-y follow-up) (all p-values < 0.001) and showed a 21% reduction in their 20-year risk of developing T2DM compared to those who were consistently away (RR = 0.79, 95%CI 0.47, 0.86). A long-term adherence to the Mediterranean diet is protective against the onset of T2DM and, therefore, could be incorporated in public health actions for the prevention of the disease.

Non-invasive tools for liver steatosis and steatohepatitis predict incidence of diabetes, cardiovascular disease and mortality 20 years later: The ATTICA cohort study (2002-2022).

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) or, as recently renamed, metabolic dysfunction-associated steatotic liver disease (MASLD), has common metabolic pathways with diabetes and cardiovascular disease (CVD). Non-invasive tools (NITs) for liver steatosis and steatohepatitis (MASH) were studied as potential predictors of diabetes, cardiovascular disease (CVD) and mortality over a 20-year period. METHODS: In 2001-02, 3042 individuals from the Attica region of Greece were recruited randomly, and were stratified by subgroups of sex, age and region to reflect the general urban population in Athens, Greece. Validated NITs for hepatic steatosis (Hepatic Steatosis Index (HIS), Fatty Liver Index (FLI), Lipid Accumulation Product (LAP), NAFLD liver fat score (NAFLD-LFS)) and steatohepatitis (Index of non-alcoholic steatohepatitis (ION), aminotransferase-creatinine-clearance non-alcoholic steatohepatitis (acNASH)) were calculated. Incidence of diabetes, CVD and mortality were recorded 5, 10 and 20 years later. RESULTS: Within a 20-year observation period, the diabetes and CVD incidence was 26.3% and 36.1%, respectively. All hepatic steatosis and steatohepatitis NITs were independently associated with diabetes incidence. ION and acNASH presented independent association with CVD incidence [(Hazard Ratio (HR)per 1 standard deviation (SD) = 1.33, 95% Confidence Interval (95% CI) (1.07, 1.99)) and (HRper 1 SD = 1.77, 95% CI (1.05, 2.59)), respectively]. NAFLD-LFS which is a steatosis NIT indicating features of steatohepatitis, was linked with increased CVD mortality (HRper 1 SD = 1.35, 95% CI (1.00, 2.30)) and all-cause mortality (HRper 1 SD = 1.43, 95% CI (1.08, 2.01)). Overall, steatohepatitis NITs (i.e., ION and acNASH) presented stronger associations with the outcomes of interest compared with steatosis NITs. Clinically important trends were observed in relation to diabetes and CVD incidence progressively over time, i.e. 5, 10 and 20 years after baseline. CONCLUSIONS: Easily applicable and low-cost NITs representing steatohepatitis may be early predictors of diabetes and CVD onset. More importantly, these NITs increased the attributable risk conveyed by conventional CVD risk factors by 10%. Thus, their potential inclusion in clinical practice and guidelines should be studied further.

Nocebo-associated treatment discontinuation with subcutaneous anti-osteoporotic drugs. A systematic review and meta-analysis of placebo-arm dropouts in randomized-controlled trials.

OBJECTIVE: Nocebo is a concept of therapeutics referring to unpleasant symptoms attributed by a patient to a drug, due to negative anticipation. Patients receiving oral anti-osteoporotic drugs in randomized controlled trials (RCT) can experience adverse events leading to dropout, implying that nocebo contributes to treatment discontinuation for these drugs. In this study we aim to investigate the nocebo effect of subcutaneous anti-osteoporotic drugs with a higher compliance rate than orally administered drugs. STUDY DESIGN: We searched MEDLINE, EMBASE, SCOPUS, and Cochrane databases for double-blind trials investigating subcutaneous anti-osteoporotic drugs for osteoporosis (namely, denosumab, teriparatide, abaloparatide and romosozumab) published up to May 2023. MAIN OUTCOME MEASURE: Dropouts due to reported adverse events in the placebo arms ("nocebo dropouts"). RESULTS: Data from 17 trials were extracted. Among 10,529 placebo-treated patients the pooled nocebo-dropout percentage was 3 % for denosumab (average: 0.03; 95 % CI: 0.01-0.05), 1 % for romosozumab (average: 0.01; 95 % CI: 0.00-0.03) and 6 % for teriparatide and abaloparatide (average: 0.06; 95 % CI: 0.05-0.07). Nocebo-dropouts were significantly higher in men than women (6 % vs. 3 %, respectively, p = 0.012), in older (mean age >68 years) than in younger patients (5 % vs. 1 %, respectively, p = 0.017) and in those with more severe osteoporosis (based on the percentage of participants with prior fragility-related fractures in the study cohort) compared with patients with no prior fracture history (4 % vs. 1 %, respectively, p = 0.046). CONCLUSION: Nocebo responses may contribute to treatment discontinuation with subcutaneous anti-osteoporotic drugs in clinical practice. Higher nocebo-related dropout rates in the higher-risk RCT population (older patients, males, those with prior fractures) show that nocebo mechanisms have the potential to hinder therapeutic efforts to specific populations who would benefit most. Prospero registration number CRD42020212843.

Discrimination and net-reclassification of cardiovascular disease risk with Lipoprotein(a) levels: The ATTICA study (2002-2022).

BACKGROUND: Lipoprotein(a) [Lp(a)] is a recognized as risk factor for atherosclerotic cardiovascular disease (ASCVD). However, its influence on clinical risk evaluations remains unclear. OBJECTIVE: This study aimed to determine whether Lp(a) improves CVD risk prediction among apparently healthy adults from the general population. METHODS: In 2002, n = 3,042 adults free of CVD, residing in Athens metropolitan area, in Greece, were recruited. A 20-year follow-up was conducted in 2022, comprising n = 2,169 participants, of which n = 1,988 had complete data for CVD incidence. RESULTS: Lp(a) levels were significantly associated with 20-year ASCVD incidence in the crude model (Hazard Ratio per 1 mg/dL: 1.004, p = 0.048), but not in multi-adjusted models considering demographic, lifestyle, and clinical factors. Adding Lp(a) to the Reynolds Risk Score (RRS) and Framingham Risk Score (FRS) variables resulted in positive Net Reclassification Improvement (NRI) values (0.159 and 0.160 respectively), indicating improved risk classification. Mediation analysis suggested that C-reactive protein, Interleukin-6, and Fibrinogen mediate the relationship between Lp(a) and ASCVD. No significant interaction was observed between Lp(a) and potential moderators. CONCLUSION: Lp(a) levels can predict 20-year CVD outcomes and improve CVD risk prediction within the general population, possibly via the intricate relationship between Lp(a), systemic inflammation, atherothrombosis.

Adherence to the Mediterranean diet and 20-year incidence of hypertension: the ATTICA prospective epidemiological study (2002-2022).

BACKGROUND/OBJECTIVES: Dietary habits are a significant predictor of hypertension (HTN). We aimed to evaluate the long-term association between adherence to the Mediterranean diet and HTN incidence. SUBJECTS/METHODS: This was a prospective study among 1415 non-hypertensive adults (44% men, age: 41 ± 13 years) followed up for 20 years. Anthropometric, lifestyle, and clinical parameters were evaluated at baseline. Adherence to the Mediterranean diet was evaluated both at baseline and 10 years through the MedDietScore (range: 0-55, higher values indicate greater adherence). RESULTS: At the 20-year follow-up, 314 new HTN cases were recorded. HTN incidence was 35.5%, 22.5%, and 8.7% in the lowest, middle, and upper tertile of baseline MedDietScore, respectively (p < 0.001). For each 1-point increase in baseline MedDietScore, the 20-year HTN risk decreased by 7% [relative risk (RR): 0.925, 95% confidence interval (CI): 0.906, 0.943], and this effect remained significant after adjustment for age, sex, and baseline lifestyle and clinical confounders, i.e., body mass index, physical activity, smoking, systolic and diastolic blood pressure, family history of HTN, and presence of hypercholesterolemia and diabetes mellitus (RR: 0.973, 95%CI: 0.949, 0.997). In a similar multiadjusted model, compared to subjects who were consistently away from the Mediterranean diet (in the lowest MedDietScore tertile both at baseline and 10 years), only those who were consistently close (in the middle and upper MedDietScore tertiles both at baseline and 10 years) exhibited a 47% lower 20-year HTN risk. CONCLUSION: A high adherence to the Mediterranean diet, particularly when longitudinally sustained, is associated with lower incidence of HTN.

The burden of cardiovascular disease and related risk factors in Greece: the ATTICA epidemiological study (2002-2022).

OBJECTIVE: The aim of this study was to present the burden of cardiovascular disease (CVD) and its related risk factors based on a 20-year observation period (2002-2022). METHODS: In 2002, 3042 Greek adults (aged: 45 (12) years) free of CVD, cancer, or any other chronic infections were enrolled. In 2022, the 20-year follow-up was performed on 2169 participants (1988 had complete data for CVD). Lifetime risk for CVDs and disability-adjusted-life-years (DALYs) lost were also calculated. RESULTS: The 20-year CVD incidence was 3600 cases/10,000 individuals (man-to-woman ratio 5:4). At the index age of 40 years, the lifetime risk for developing CVD was 68% for men and 63% for women; as the participants were getting older, the lifetime risk declined by approximately 19% and 13% for men and women, respectively, but remained at high levels, reaching 55% for both sexes. Participants between 45 and 55 years exhibited the highest CVD burden concerning aggregated DALYs. The burden was greater in men than in women, at ages below 35 years; beyond this age threshold, this trend shifted, and women exhibited a higher CVD burden. CONCLUSION: The burden of CVD in Greece has shown increasing trends over the past 20 years as a result of the accumulative growth of the prevalence of modifiable CVD risk factors. The disability-adjusted life-years lost are the most observed ever before, urging for efficient public health strategies and measures.

Mediterranean-Type Diet Adherence and Body Mass Index through 20 Years of Follow-Up: Results from the ATTICA Cohort Study (2002-2022).

Evidence of the association between dietary habits and long-term body weight status is scarce. This study aimed to evaluate changes in Mediterranean-type diet (MTD) adherence in relation to body weight during 20 years of follow-up. Data from n = 1582 participants from the ATTICA cohort study (2002-2022) were used. MTD adherence was assessed via MedDietScore, and body weight status via body mass index (BMI) by 3 different measurements. We found that MTD adherence and changes in this adherence were inversely related to BMI at 20 years and the mean BMI during the 20-year follow-up. In multi-adjusted linear regression models, a 1/55 increase in baseline, 10-year, and 20-year MedDietScore was associated with a decrease of 0.05-0.13 kg/m2 in BMI at 20 years and of 0.08-0.09 kg/m2 in the mean BMI. Being consistently close to the MTD for 20 years was associated with a >90% decreased risk of maintaining overweight/obesity during the 20-year period. Strong, protective, long-lasting effects of the MTD were observed, even in those who deviated from the MTD in the follow-up (41% of the sample). Our results highlight the need to focus on the overall diet quality to minimize the risk of maintaining an excessive body weight during the life-course.