C-reactive protein modifies lipoprotein(a)-related risk for coronary heart disease: the BiomarCaRE project.

BACKGROUND AND AIMS: Recent investigations have suggested an interdependence of lipoprotein(a) [Lp(a)]-related risk for cardiovascular disease with background inflammatory burden. The aim the present analysis was to investigate whether high-sensitive C-reactive protein (hsCRP) modulates the association between Lp(a) and coronary heart disease (CHD) in the general population. METHODS: Data from 71 678 participants from 8 European prospective population-based cohort studies were used (65 661 without/6017 with established CHD at baseline; median follow-up 9.8/13.8 years, respectively). Fine and Gray competing risk-adjusted models were calculated according to accompanying hsCRP concentration (<2 and ≥2 mg/L). RESULTS: Among CHD-free individuals, increased Lp(a) levels were associated with incident CHD irrespective of hsCRP concentration: fully adjusted sub-distribution hazard ratios [sHRs (95% confidence interval)] for the highest vs. lowest fifth of Lp(a) distribution were 1.45 (1.23-1.72) and 1.48 (1.23-1.78) for a hsCRP group of <2 and ≥2 mg/L, respectively, with no interaction found between these two biomarkers on CHD risk (Pinteraction = 0.82). In those with established CHD, similar associations were seen only among individuals with hsCRP ≥ 2 mg/L [1.34 (1.03-1.76)], whereas among participants with a hsCRP concentration <2 mg/L, there was no clear association between Lp(a) and future CHD events [1.29 (0.98-1.71)] (highest vs. lowest fifth, fully adjusted models; Pinteraction = 0.024). CONCLUSIONS: While among CHD-free individuals Lp(a) was significantly associated with incident CHD regardless of hsCRP, in participants with CHD at baseline, Lp(a) was related to recurrent CHD events only in those with residual inflammatory risk. These findings might guide adequate selection of high-risk patients for forthcoming Lp(a)-targeting compounds.

Prognostic Value of Cardiovascular Biomarkers in the Population.

Importance: Identification of individuals at high risk for atherosclerotic cardiovascular disease within the population is important to inform primary prevention strategies. Objective: To evaluate the prognostic value of routinely available cardiovascular biomarkers when added to established risk factors. Design, Setting, and Participants: Individual-level analysis including data on cardiovascular biomarkers from 28 general population-based cohorts from 12 countries and 4 continents with assessments by participant age. The median follow-up was 11.8 years. Exposure: Measurement of high-sensitivity cardiac troponin I, high-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide, B-type natriuretic peptide, or high-sensitivity C-reactive protein. Main Outcomes and Measures: The primary outcome was incident atherosclerotic cardiovascular disease, which included all fatal and nonfatal events. The secondary outcomes were all-cause mortality, heart failure, ischemic stroke, and myocardial infarction. Subdistribution hazard ratios (HRs) for the association of biomarkers and outcomes were calculated after adjustment for established risk factors. The additional predictive value of the biomarkers was assessed using the C statistic and reclassification analyses. Results: The analyses included 164 054 individuals (median age, 53.1 years [IQR, 42.7-62.9 years] and 52.4% were women). There were 17 211 incident atherosclerotic cardiovascular disease events. All biomarkers were significantly associated with incident atherosclerotic cardiovascular disease (subdistribution HR per 1-SD change, 1.13 [95% CI, 1.11-1.16] for high-sensitivity cardiac troponin I; 1.18 [95% CI, 1.12-1.23] for high-sensitivity cardiac troponin T; 1.21 [95% CI, 1.18-1.24] for N-terminal pro-B-type natriuretic peptide; 1.14 [95% CI, 1.08-1.22] for B-type natriuretic peptide; and 1.14 [95% CI, 1.12-1.16] for high-sensitivity C-reactive protein) and all secondary outcomes. The addition of each single biomarker to a model that included established risk factors improved the C statistic. For 10-year incident atherosclerotic cardiovascular disease in younger people (aged <65 years), the combination of high-sensitivity cardiac troponin I, N-terminal pro-B-type natriuretic peptide, and high-sensitivity C-reactive protein resulted in a C statistic improvement from 0.812 (95% CI, 0.8021-0.8208) to 0.8194 (95% CI, 0.8089-0.8277). The combination of these biomarkers also improved reclassification compared with the conventional model. Improvements in risk prediction were most pronounced for the secondary outcomes of heart failure and all-cause mortality. The incremental value of biomarkers was greater in people aged 65 years or older vs younger people. Conclusions and Relevance: Cardiovascular biomarkers were strongly associated with fatal and nonfatal cardiovascular events and mortality. The addition of biomarkers to established risk factors led to only a small improvement in risk prediction metrics for atherosclerotic cardiovascular disease, but was more favorable for heart failure and mortality.

Drinking alcohol in moderation is associated with lower rate of all-cause mortality in individuals with higher rather than lower educational level: findings from the MORGAM project.

The association between socioeconomic status (SES) and alcohol-related diseases has been widely explored. Less is known, however, on whether the association of moderate drinking with all-cause mortality is modified by educational level (EL). Using harmonized data from 16 cohorts in the MORGAM Project (N = 142,066) the association of pattern of alcohol intake with hazard of all-cause mortality across EL (lower = primary-school; middle = secondary-school; higher = university/college degree) was assessed using multivariable Cox-regression and spline curves. A total of 16,695 deaths occurred in 11.8 years (median). In comparison with life-long abstainers, participants drinking 0.1-10 g/d of ethanol had 13% (HR = 0.87; 95%CI: 0.74-1.02), 11% (HR = 0.89; 0.84-0.95) and 5% (HR = 0.95; 0.89-1.02) lower rate of death in higher, middle and lower EL, respectively. Conversely, drinkers > 20 g/d had 1% (HR = 1.01; 0.82-1.25), 10% (HR = 1.10; 1.02-1.19) and 17% (HR = 1.17; 1.09-1.26) higher rate of death. The association of alcohol consumption with all-cause mortality was nonlinear, with a different J-shape by EL levels. It was consistent across both sexes and in various approaches of measuring alcohol consumption, including combining quantity and frequency and it was more evident when the beverage of preference was wine. We observed that drinking in moderation (≤ 10 g/d) is associated with lower mortality rate more evidently in individuals with higher EL than in people with lower EL, while heavy drinking is associated with higher mortality rate more evidently in individuals with lower EL than in people with higher EL, suggesting that advice on reducing alcohol intake should especially target individuals of low EL.

Humoral and Cellular Immune Response Elicited by the BNT162b2 COVID-19 Vaccine Booster in Elderly.

Although the safety and efficacy of COVID-19 vaccines in older people are critical to their success, little is known about their immunogenicity among elderly residents of long-term care facilities (LTCFs). A single-center prospective cohort study was conducted: a total IgG antibody titer, neutralizing antibodies against Wild-type, Delta Plus, and Omicron BA.2 variants and T cell response, were measured eight months after the second dose of BNT162b2 vaccine (T0) and at least 15 days after the booster (T1). Forty-nine LTCF residents, with a median age of 84.8 ± 10.6 years, were enrolled. Previous COVID-19 infection was documented in 42.9% of the subjects one year before T0. At T1, the IgG titers increased up to 10-fold. This ratio was lower in the subjects with previous COVID-19 infection. At T1, IgG levels were similar in both groups. The neutralizing activity against Omicron BA.2 was significantly lower (65%) than that measured against Wild-type and Delta Plus (90%). A significant increase of T cell-specific immune response was observed after the booster. Frailty, older age, sex, cognitive impairment, and comorbidities did not affect antibody titers or T cell response. In the elderly sample analyzed, the BNT162b2 mRNA COVID-19 vaccine produced immunogenicity regardless of frailty.

Influence of geographical latitude on vitamin D status: cross-sectional results from the BiomarCaRE consortium.

Even though sunlight is viewed as the most important determinant of 25-hydroxyvitamin D (25(OH)D) status, several European studies have observed higher 25(OH)D concentrations among north-Europeans than south-Europeans. We studied the association between geographical latitude (derived from ecological data) and 25(OH)D status in six European countries using harmonised immunoassay data from 81 084 participants in the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project (male sex 48·9 %; median age 50·8 years; examination period 1984-2014). Quantile regression models, adjusted for age, sex, decade and calendar week of sampling and time from sampling to analysis, were used for between-country comparisons. Up until the median percentile, the ordering of countries by 25(OH)D status (from highest to lowest) was as follows: Sweden (at 65·6-63·8°N), Germany (at 48·4°N), Finland (at 65·0-60·2°N), Italy (at 45·6-41·5°N), Scotland (at 58·2-55·1°N) and Spain (at 41·5°N). From the 75th percentile and upwards, Finland had higher values than Germany. As an example, using the Swedish cohort as a comparator, the median 25(OH)D concentration was 3·03, 3·28, 5·41, 6·54 and 9·28 ng/ml lower in the German, Finnish, Italian, Scottish and Spanish cohort, respectively (P-value < 0·001 for all comparisons). The ordering of countries was highly consistent in subgroup analyses by sex, age, and decade and season of sampling. In conclusion, we confirmed the previous observation of a north-to-south gradient of 25(OH)D status in Europe, with higher percentile values among north-Europeans than south-Europeans.

Long-term exposure to air pollution and COVID-19 incidence: a prospective study of residents in the city of Varese, Northern Italy.

OBJECTIVES: To investigate the association between long-term exposure to airborne pollutants and the incidence of SARS-CoV-2 up to March 2021 in a prospective study of residents in Varese city. METHODS: Citizens of Varese aged ≥18 years as of 31 December 2019 were linked by residential address to 2018 average annual exposure to outdoor concentrations of PM2.5, PM10, NO2, NO and ozone modelled using the Flexible Air quality Regional Model (FARM) chemical transport model. Citizens were further linked to regional datasets for COVID-19 case ascertainment (positive nasopharyngeal swab specimens) and to define age, sex, living in a residential care home, population density and comorbidities. We estimated rate ratios and additional numbers of cases per 1 µg/m3 increase in air pollutants from single- and bi-pollutant Poisson regression models. RESULTS: The 62 848 residents generated 4408 cases. Yearly average PM2.5 exposure was 12.5 µg/m3. Age, living in a residential care home, history of stroke and medications for diabetes, hypertension and obstructive airway diseases were independently associated with COVID-19. In single-pollutant multivariate models, PM2.5 was associated with a 5.1% increase in the rate of COVID-19 (95% CI 2.7% to 7.5%), corresponding to 294 additional cases per 100 000 person-years. The association was confirmed in bi-pollutant models; excluding subjects in residential care homes; and further adjusting for area-based indicators of socioeconomic level and use of public transportation. Similar findings were observed for PM10, NO2 and NO. Ozone was associated with a 2% decrease in disease rate, the association being reversed in bi-pollutant models. CONCLUSIONS: Long-term exposure to low levels of air pollutants, especially PM2.5, increased the incidence of COVID-19. The causality warrants confirmation in future studies; meanwhile, government efforts to further reduce air pollution should continue.

Association of glycated hemoglobin A1c levels with cardiovascular outcomes in the general population: results from the BiomarCaRE (Biomarker for Cardiovascular Risk Assessment in Europe) consortium.

BACKGROUND: Biomarkers may contribute to improved cardiovascular risk estimation. Glycated hemoglobin A1c (HbA1c) is used to monitor the quality of diabetes treatment. Its strength of association with cardiovascular outcomes in the general population remains uncertain. This study aims to assess the association of HbA1c with cardiovascular outcomes in the general population. METHODS: Data from six prospective population-based cohort studies across Europe comprising 36,180 participants were analyzed. HbA1c was evaluated in conjunction with classical cardiovascular risk factors (CVRFs) for association with cardiovascular mortality, cardiovascular disease (CVD) incidence, and overall mortality in subjects without diabetes (N = 32,496) and with diabetes (N = 3684). RESULTS: Kaplan-Meier curves showed higher event rates with increasing HbA1c levels (log-rank-test: p < 0.001). Cox regression analysis revealed significant associations between HbA1c (in mmol/mol) in the total study population and the examined outcomes. Thus, a hazard ratio (HR) of 1.16 (95% confidence interval (CI) 1.02-1.31, p = 0.02) for cardiovascular mortality, 1.13 (95% CI 1.03-1.24, p = 0.01) for CVD incidence, and 1.09 (95% CI 1.02-1.17, p = 0.01) for overall mortality was observed per 10 mmol/mol increase in HbA1c. The association with CVD incidence and overall mortality was also observed in study participants without diabetes with increased HbA1c levels (HR 1.12; 95% CI 1.01-1.25, p = 0.04) and HR 1.10; 95% CI 1.01-1.20, p = 0.02) respectively. HbA1c cut-off values of 39.9 mmol/mol (5.8%), 36.6 mmol/mol (5.5%), and 38.8 mmol/mol (5.7%) for cardiovascular mortality, CVD incidence, and overall mortality, showed also an increased risk. CONCLUSIONS: HbA1c is independently associated with cardiovascular mortality, overall mortality and cardiovascular disease in the general European population. A mostly monotonically increasing relationship was observed between HbA1c levels and outcomes. Elevated HbA1c levels were associated with cardiovascular disease incidence and overall mortality in participants without diabetes underlining the importance of HbA1c levels in the overall population.

Identification of dietary patterns in a general population of North Italian adults and their association with arterial stiffness. The RoCAV study.

BACKGROUND AND AIMS: The aims of this study were to identify dietary patterns in a general population of North Italian adults and to investigate the cross-sectional association between prevalent dietary patterns and arterial stiffness. METHODS AND RESULTS: Participants to the RoCAV study without chronic diseases at recruitment and with reliable dietary data were included. The food-frequency EPIC questionnaire was used to evaluate dietary habits. Dietary patterns were estimated using principal components analysis and Mediterranean diet adherence score (MedS). Carotid-femoral pulse wave velocity (cfPWV) was used as proxy of arterial stiffness. Basing on data from 2640 subjects (1608 men and 1032 women, mean ± SD 65.5 ± 6.7 years), four principal components (PC) were retained, explaining 24% of the overall variance. Considering 1284 subjects with cfPWV (mean ± SD 10.7 ± 2.5 m/s) data available, adherence to PC1 (Western-like dietary pattern) was associated with higher stiffness values (+0.29 m/s cfPWV for 1 SD increase of PC1, 95% CI:0.08,0.50; p = 0.007) in a multivariate model. Conversely, adherence to PC2 (Mediterranean-like) was not related to cfPWV values (-0.18, 95% CI: -0.36, 0.004; p = 0.06). Likewise, MedS and other PC patterns did not show any significant association with cfPWV. Mediation analysis showed that the association between Western-like dietary pattern and cfPWV is mediated by higher levels of leucocytes (9.2% of the effect, p = 0.047). CONCLUSIONS: Our study in a Southern European population identified a Western-like dietary pattern associated with an increased cfPWV, a proxy of arterial stiffness. The association with cfPWV was in part mediated by inflammatory status.

Development and validation of two SCORE-based cardiovascular risk prediction models for Eastern Europe: a multicohort study.

AIMS: Cardiovascular disease (CVD) risk prediction models are used in Western European countries, but less so in Eastern European countries where rates of CVD can be two to four times higher. We recalibrated the SCORE prediction model for three Eastern European countries and evaluated the impact of adding seven behavioural and psychosocial risk factors to the model. METHODS AND RESULTS: We developed and validated models using data from the prospective HAPIEE cohort study with 14 598 participants from Russia, Poland, and the Czech Republic (derivation cohort, median follow-up 7.2 years, 338 fatal CVD cases) and Estonian Biobank data with 4632 participants (validation cohort, median follow-up 8.3 years, 91 fatal CVD cases). The first model (recalibrated SCORE) used the same risk factors as in the SCORE model. The second model (HAPIEE SCORE) added education, employment, marital status, depression, body mass index, physical inactivity, and antihypertensive use. Discrimination of the original SCORE model (C-statistic 0.78 in the derivation and 0.83 in the validation cohorts) was improved in recalibrated SCORE (0.82 and 0.85) and HAPIEE SCORE (0.84 and 0.87) models. After dichotomizing risk at the clinically meaningful threshold of 5%, and when comparing the final HAPIEE SCORE model against the original SCORE model, the net reclassification improvement was 0.07 [95% confidence interval (CI) 0.02-0.11] in the derivation cohort and 0.14 (95% CI 0.04-0.25) in the validation cohort. CONCLUSION: Our recalibrated SCORE may be more appropriate than the conventional SCORE for some Eastern European populations. The addition of seven quick, non-invasive, and cheap predictors further improved prediction accuracy.

Occupational class differences in ankle-brachial index and pulse wave velocity measurements to detect subclinical vascular disease.

BACKGROUND: High pulse wave velocity (PWV) and low ankle brachial index (ABI) have been proposed as surrogate end-points for cardiovascular disease (CVD). OBJECTIVES: In a cross-sectional setting, we aimed at assessing the distributions of PWV and ABI among occupational classes (OC) in a population-based ever-employed salaried sample. METHODS: We enrolled 1388 salaried CVD-free workers attending a CVD population-based survey, the RoCAV study, and classified them into four OC, based on current or last job title: manager/director (MD), non-manual (NMW), skilled-manual (SMW) and (UMW) unskilled-manual workers. We derived brachial-ankle PWV and ABI from four-limb blood pressures measurements, then carotid-femoral PWV (cfPWV) was estimated. We estimated the OC gradients in cfPWV and ABI using linear and logistic regression models. RESULTS: Compared to MD (reference category), UMW had higher age- and BMI-adjusted cfPWV mean values both in men (0.63 m/s; 95%CI:0.11-1.16) and women (1.60 m/s; 0.43-2.77), only marginally reduced when adjusting for CVD risk factors. Decreased ABI mean values were also detected in lower OC. The overall detection rate of abnormal cfPWV (≥12 m/s) or ABI (≤0.9) values was 28%. Compared to MD, the prevalence of abnormal cfPWV or ABI was higher in NMW (OR=1.77; 95%CI:1.12-2.79), SMW (1.71; 1.05-2.78) and UMW (2.72; 1.65-4.50). Adjustment for CVD risk factors used in risk score equations did not change the results. DISCUSSION: We found a higher prevalence of abnormal values of arterial stiffness measures in lower OC, and these differences were not explained by traditional CVD risk factors. These may be presumably determined by additional work- and environmental-related risk factors.

Application of non-HDL cholesterol for population-based cardiovascular risk stratification: results from the Multinational Cardiovascular Risk Consortium.

BACKGROUND: The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment. METHODS: In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol. FINDINGS: Of the 524 444 individuals in the 44 cohorts in the Consortium database, we identified 398 846 individuals belonging to 38 cohorts (184 055 [48·7%] women; median age 51·0 years [IQR 40·7-59·7]). 199 415 individuals were included in the derivation cohort (91 786 [48·4%] women) and 199 431 (92 269 [49·1%] women) in the validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years, IQR 7·0-20·1), 54 542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol <2·6 mmol/L to 33·7% for ≥5·7 mmol/L in women and from 12·8% to 43·6% in men; p<0·0001). Multivariable adjusted Cox models with non-HDL cholesterol lower than 2·6 mmol/L as reference showed an increase in the association between non-HDL cholesterol concentration and cardiovascular disease for both sexes (from hazard ratio 1·1, 95% CI 1·0-1·3 for non-HDL cholesterol 2·6 to <3·7 mmol/L to 1·9, 1·6-2·2 for ≥5·7 mmol/L in women and from 1·1, 1·0-1·3 to 2·3, 2·0-2·5 in men). The derived tool allowed the estimation of cardiovascular disease event probabilities specific for non-HDL cholesterol with high comparability between the derivation and validation cohorts as reflected by smooth calibration curves analyses and a root mean square error lower than 1% for the estimated probabilities of cardiovascular disease. A 50% reduction of non-HDL cholesterol concentrations was associated with reduced risk of a cardiovascular disease event by the age of 75 years, and this risk reduction was greater the earlier cholesterol concentrations were reduced. INTERPRETATION: Non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic cardiovascular disease. We provide a simple tool for individual long-term risk assessment and the potential benefit of early lipid-lowering intervention. These data could be useful for physician-patient communication about primary prevention strategies. FUNDING: EU Framework Programme, UK Medical Research Council, and German Centre for Cardiovascular Research.

NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) and the Risk of Stroke.

Background and Purpose- NT-proBNP (N-terminal pro-B-type natriuretic peptide) is a risk factor for atrial fibrillation and a marker of cardiac function used in the detection of heart failure. Given the link between cardiac dysfunction and stroke, NT-proBNP is a candidate marker of stroke risk. Our aim was to evaluate the association of NT-proBNP with stroke and to determine the predictive value beyond a panel of established risk factors. Methods- Based on the Biomarkers for Cardiovascular Risk Assessment in Europe-Consortium, we analyzed data of 58 173 participants (50% men; mean age 52 y) free of stroke from 6 community-based cohorts. NT-proBNP measurements were performed in the central Biomarkers for Cardiovascular Risk Assessment in Europe laboratory. The outcomes considered were total stroke and subtypes of stroke (ischemic/hemorrhagic). Results- During a median follow-up time of 7.9 years, we observed 1550 stroke events (1176 ischemic). Increasing quarters of the NT-proBNP distribution were associated with increasing risk of stroke ( P for trend <0.0001; multivariable Cox regression analysis adjusted for risk factors and cardiac diseases). Individuals in the highest NT-proBNP quarter (NT-proBNP >82.2 pg/mL) had 2-fold (95% CI, 75%-151%) greater risk of stroke than individuals in the lowest quarter (NT-proBNP <20.4 pg/mL). The association remained unchanged when adjusted for interim coronary events during follow-up, and though it was somewhat heterogeneous across cohorts, it was highly homogenous according to cardiovascular risk profile or subtypes of stroke. The addition of NT-proBNP to a reference model increased the C-index discrimination measure by 0.006 ( P=0.0005), yielded a categorical net reclassification improvement of 2.0% in events and 1.4% in nonevents and an integrated discrimination improvement of 0.007. Conclusions- In European individuals free of stroke, levels of NT-proBNP are positively associated with risk of ischemic and hemorrhagic stroke, independently from several other risk factors and conditions. The addition of NT-proBNP to variables of established risk scores improves prediction of stroke, with a medium effect size.

Is there an association between drugs and burning mouth syndrome? A case-control study.

OBJECTIVE: The purpose of this case-control study was to compare the pharmacological anamnesis collected from a group of 150 burning mouth syndrome (BMS) patients with that of a control group of 150 patients matched for age and sex. MATERIALS AND METHODS: The patients' medical histories were reviewed, and data on drug therapy were collected. Drugs were classified on the basis of pharmacological effects; the classes were antihypertensives (i.e., ACE inhibitors/ARBs, calcium antagonists, diuretics and beta-blockers), antiaggregants, anticoagulants, antidiabetics, vitamin D integrators, bisphosphonates, psychotropics (i.e., anxiolytics and antidepressants), gastroprotectors, statins, thyroid hormone substitutes, corticosteroids and immunosuppressants. RESULTS: The BMS patients and the controls were matched for age (mean age: 69 years) and sex (128 females and 22 males). Antihypertensives, especially ACE inhibitors/ARBs (OR = 0.37, CI: 0.22-0.63, p = 0.0002) and beta-blockers (OR = 0.36, CI: 0.19-0.68 p = 002), revealed an inverse association with the presence of BMS, whereas anxiolytics (OR = 3.78, CI: 2.12-6.75 p < 0.0001), but neither antidepressants nor antipsychotics, were significantly associated with BMS. There were no correlations with other drug classes. CONCLUSION: Our study highlighted that ACE inhibitors, ARBs and beta-blockers were in inverse relation to BMS and found that anxiolytics, but neither antidepressants nor antipsychotics, were linked to the presence of the syndrome.

Trueness and precision of 5 intraoral scanners in the impressions of single and multiple implants: a comparative in vitro study.

BACKGROUND: Until now, a few studies have addressed the accuracy of intraoral scanners (IOSs) in implantology. Hence, the aim of this in vitro study was to assess the accuracy of 5 different IOSs in the impressions of single and multiple implants, and to compare them. METHODS: Plaster models were prepared, representative of a partially edentulous maxilla (PEM) to be restored with a single crown (SC) and a partial prosthesis (PP), and a totally edentulous maxilla (TEM) to be restored with a full-arch (FA). These models were scanned with a desktop scanner, to capture reference models (RMs), and with 5 IOSs (CS 3600®, Trios3®, Omnicam®, DWIO®, Emerald®); 10 scans were taken for each model, using each IOS. All IOS datasets were loaded into a reverse-engineering software where they were superimposed on the corresponding RMs, to evaluate trueness, and superimposed on each other within groups, to determine precision. A statistical analysis was performed. RESULTS: In the SC, CS 3600® had the best trueness (15.2 ± 0.8 µm), followed by Trios3® (22.3 ± 0.5 µm), DWIO® (27.8 ± 3.2 µm), Omnicam® (28.4 ± 4.5 µm), Emerald® (43.1 ± 11.5 µm). In the PP, CS 3600® had the best trueness (23 ± 1.1 µm), followed by Trios3® (28.5 ± 0.5 µm), Omnicam® (38.1 ± 8.8 µm), Emerald® (49.3 ± 5.5 µm), DWIO® (49.8 ± 5 µm). In the FA, CS 3600® had the best trueness (44.9 ± 8.9 µm), followed by Trios3® (46.3 ± 4.9 µm), Emerald® (66.3 ± 5.6 µm), Omnicam® (70.4 ± 11.9 µm), DWIO® (92.1 ± 24.1 µm). Significant differences were found between the IOSs; a significant difference in trueness was found between the contexts (SC vs. PP vs. FA). In the SC, CS 3600® had the best precision (11.3 ± 1.1 µm), followed by Trios3® (15.2 ± 0.8 µm), DWIO® (27.1 ± 10.7 µm), Omnicam® (30.6 ± 3.3 µm), Emerald® (32.8 ± 10.7 µm). In the PP, CS 3600® had the best precision (17 ± 2.3 µm), followed by Trios3® (21 ± 1.9 µm), Emerald® (29.9 ± 8.9 µm), DWIO® (34.8 ± 10.8 µm), Omnicam® (43.2 ± 9.4 µm). In the FA, Trios3® had the best precision (35.6 ± 3.4 µm), followed by CS 3600® (35.7 ± 4.3 µm), Emerald® (61.5 ± 18.1 µm), Omnicam® (89.3 ± 14 µm), DWIO® (111 ± 24.8 µm). Significant differences were found between the IOSs; a significant difference in precision was found between the contexts (SC vs. PP vs. FA). CONCLUSIONS: The IOSs showed significant differences between them, both in trueness and in precision. The mathematical error increased in the transition from SC to PP up to FA, both in trueness than in precision.

Allostatic load as a mediator of the association between psychosocial risk factors and cardiovascular diseases. Recent evidence and indications for prevention.

SUMMARY: Aims. Some categories of workers are more vulnerable to the detrimental effect of job strain on cardiovascular risk. We investigate allostatic load, the physiological "wear and tear" resulting from adaptation to chronic stress, as a candidate pathway to explain such vulnerability. Methods. We selected 25-64 years old salaried workers participants to three population-based cohorts. We defined allostatic load (AL) as the sum of z-scores of 9 selected biomarkers; occupational classes (OCs) from the Erikson- Goldthorpe-Portocarero schema; and job strain (JS) according to Karasek's demand-control model. We adopted the Oaxaca- Blinder decomposition to disentangle the OC gradient in AL into the differential exposure (attributable to different JS prevalence across OCs) and the differential vulnerability (attributable to a different effect of JS on AL across OCs) components. Results. In the n=2010 workers (62% men, 34% manuals), OCs, but not JS categories, were associated with AL, independently of age and gender (p-value: 0.02). In the overall sample, JS did not have an effect on the OC gradient in AL. Conversely, in workers with sleep impairment, depression, or not engaged into physical activity, JS had a positive differential vulnerability coefficient of 0.63 (95%CI 0.05 to 1.21). Conclusions. In manual workers with impaired capacity of response, job strain is associated with a disproportional allostatic load accumulation.

Prevalence of Abdominal Aortic Aneurysms in the General Population and in Subgroups at High Cardiovascular Risk in Italy. Results of the RoCAV Population Based Study.

OBJECTIVES: Prevalence data on abdominal aortic aneurysm (AAA) in women, subjects younger than 65 years and in subgroups carrying specific risk factors are scarce. AAA prevalence was evaluated in an Italian population including women and younger subjects, stratifying for the presence of cardiovascular disease (CVD) risk factors and CVD risk score. MATERIALS AND METHODS: A population based cross-sectional study was conducted between 2013 and 2016. Men aged 50-75 and women aged 60-75 years, resident in the city of Varese (northern Italy), were randomly selected from the civil registry. A vascular surgeon performed an abdominal aortic ultrasound scan at four sites using the leading edge to leading edge method. CVD risk score was computed using the ESC-SCORE algorithm. The age and gender specific prevalence was estimated, stratifying by the presence of CVD and cardiovascular risk factors. RESULTS: Among the 3755 subjects with a valid ultrasound measurement, 63 subjects with an AAA were identified (5 referred for surgical intervention), among whom 34 were not previously known (30 men 1.3%, 95% CI 0.9-1.8; 4 women 0.3%, 95% CI 0.1-0.8). Considering age classes in men only, the highest prevalence of screen detected AAA was found in subjects aged 65-70 (1.2%; 95% CI 0.4-2.5) and 70-75 (2.5%; 95% CI 1.4-4.0) years. Among 65-75 year old men, the highest AAA prevalence was found in subjects with a previous myocardial infarction (MI 4.9%, 95% CI 2.0-9.9) and in ever-smokers reporting more than 15 pack years of smoking (4.1%, 95% CI 2.5-6.3). Among the younger subjects, those having an ESC-SCORE higher than 5% or a previous CVD (MI or stroke) showed a prevalence of 1.4% (95% CI 0.3-4.2; prevalence including subaneurysms 6.7%, 95% CI 3.7-11.0%). CONCLUSIONS: In the study population, both a general screening program in 65-75 year old men and an approach targeted to subgroups at higher risk merit evaluation in a cost-effectiveness study. In 50-64 year old men, strategies for population selection should consider CVD risk stratification tools.

Monitoring quality of care in acute myocardial infarction patients using retrospective registry data.

BACKGROUND: Hospital-based registries provide a key contribution in assessing the quality of care in acute myocardial infarction (MI) patients, although some concern on selection bias of included cases has recently arisen. We investigated the feasibility of a retrospective, population-based registry of MIs in monitoring the quality of care. METHODS: We identified all the hospitalizations with a diagnosis of acute MI among 35-79 years old residents in the Varese province, Northern Italy, in 2007-2008. Information needed to define performance according to the American Heart Association set was extracted from hospital case histories. To characterize our approach, we focus on data completeness for critical event times and eligibility criteria, and on the analysis of ST-elevated MI (STEMI) patients according to received reperfusion treatment. RESULTS: Exact time of hospital admission and of percutaneous coronary angioplasty (PCI) procedure was available in 96% and 77% of MIs, with no difference between non-transferred (n = 1399) and inter-hospital transferred (n = 300) patients. Data completeness for eligibility to action/treatment criteria was >90% for each performance measure except statin prescription at discharge (76%). About 45% of STEMI experienced a delay in PCI-capable hospital arrival, and only one every three ST-elevated MI patients received primary PCI; these were more likely to be younger male cases with less comorbidities than un-treated patients. CONCLUSIONS: Complementary to clinical registries, the retrospective population-based is a feasible approach which allows monitoring the entire pattern of care of all hospitalized MI patients independent of their clinical characteristics.

Lipoprotein(a) and the risk of cardiovascular disease in the European population: results from the BiomarCaRE consortium.

AIMS: As promising compounds to lower Lipoprotein(a) (Lp(a)) are emerging, the need for a precise characterization and comparability of the Lp(a)-associated cardiovascular risk is increasing. Therefore, we aimed to evaluate the distribution of Lp(a) concentrations across the European population, to characterize the association with cardiovascular outcomes and to provide high comparability of the Lp(a)-associated cardiovascular risk by use of centrally determined Lp(a) concentrations. METHODS AND RESULTS: Based on the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE)-project, we analysed data of 56 804 participants from 7 prospective population-based cohorts across Europe with a maximum follow-up of 24 years. All Lp(a) measurements were performed in the central BiomarCaRE laboratory (Biokit Quantia Lp(a)-Test; Abbott Diagnostics). The three endpoints considered were incident major coronary events (MCE), incident cardiovascular disease (CVD) events, and total mortality. We found lower Lp(a) levels in Northern European cohorts (median 4.9 mg/dL) compared to central (median 7.9 mg/dL) and Southern European cohorts (10.9 mg/dL) (Jonckheere-Terpstra test P < 0.001). Kaplan-Meier curves showed the highest event rate of MCE and CVD events for Lp(a) levels ≥90th percentile (log-rank test: P < 0.001 for MCE and CVD). Cox regression models adjusted for age, sex, and cardiovascular risk factors revealed a significant association of Lp(a) levels with MCE and CVD with a hazard ratio (HR) of 1.30 for MCE [95% confidence interval (CI) 1.15‒1.46] and of 1.25 for CVD (95% CI 1.12‒1.39) for Lp(a) levels in the 67‒89th percentile and a HR of 1.49 for MCE (95% CI 1.29‒1.73) and of 1.44 for CVD (95% CI 1.25‒1.65) for Lp(a) levels ≥ 90th percentile vs. Lp(a) levels in the lowest third (P < 0.001 for all). There was no significant association between Lp(a) levels and total mortality. Subgroup analysis for a continuous version of cube root transformed Lp(a) identified the highest Lp(a)-associated risk in individuals with diabetes [HR for MCE 1.31 (95% CI 1.15‒1.50)] and for CVD 1.22 (95% CI 1.08‒1.38) compared to those without diabetes [HR for MCE 1.15 (95% CI 1.08‒1.21; HR for CVD 1.13 (1.07-1.19)] while no difference of the Lp(a)- associated risk were seen for other cardiovascular high risk states. The addition of Lp(a) levels to a prognostic model for MCE and CVD revealed only a marginal but significant C-index discrimination measure increase (0.001 for MCE and CVD; P < 0.05) and net reclassification improvement (0.010 for MCE and 0.011 for CVD). CONCLUSION: In this large dataset on harmonized Lp(a) determination, we observed regional differences within the European population. Elevated Lp(a) was robustly associated with an increased risk for MCE and CVD in particular among individuals with diabetes. These results may lead to better identification of target populations who might benefit from future Lp(a)-lowering therapies.

Short (6-mm) dental implants versus sinus floor elevation and placement of longer (≥10-mm) dental implants: a randomized controlled trial with a 3-year follow-up.

OBJECTIVES: To investigate whether short (6-mm) dental implants could be an alternative to sinus floor elevation (SFE) and placement of longer (≥10-mm) implants in the posterior maxilla. MATERIALS AND METHODS: Over a 3-year period, all patients presenting with partial edentulism in the posterior maxilla were considered for inclusion in this randomized controlled trial. Patients were randomly chosen either to receive short (6-mm) implants (test group [TG]) or to undergo SFE with simultaneous placement of standard-length (≥10-mm) implants (control group [CG]). SFE was performed using the lateral technique. In both groups, tapered implants (AnyRidge, MegaGen, Gyeongbuk, South Korea) were placed. All implants were loaded after 4 months of healing. At each annual follow-up session, clinical and radiographic parameters were assessed. Primary outcomes were implant survival, stability (measured with the implant stability quotient [ISQ]), marginal bone loss (MBL), and complications; secondary outcomes were patient satisfaction and treatment time and cost. RESULTS: Thirty-three patients were assigned to the TG and 20 to the CG. Forty-five implants were inserted in each group. At 3 years, implant survival rates were 100% and 95.0% for the TG and CG, respectively; this difference was not statistically significant (P = 0.38). The mean ISQ values of the TG and CG did not differ at placement (68.2 vs. 67.8, P = 0.1), at delivery of the final restoration (69.5 vs. 69.4, P = 0.9), and after 1 year (71.0 vs. 71.5, P = 0.1); at 3 years, the CG had a significantly higher mean ISQ than the TG (72.4 vs. 71.6, P = 0.004). Mean MBL was significantly higher in the CG than in the TG, both at 1 year (0.14 mm vs. 0.21 mm, P = 0.006) and at 3 years (0.20 mm vs. 0.27 mm, P = 0.01). A few complications were reported. Surgical time and cost were significantly higher in the CG than in the TG (P < 0.0001). Patient satisfaction was high in both groups. CONCLUSIONS: In this randomized controlled trial, results for short (6-mm) implants were similar to those for longer (≥10-mm) implants in augmented bone. Short implants might be preferable to SFE, because the treatment is faster and less expensive. Long-term randomized controlled trials are required to confirm these results.

Troponin I and cardiovascular risk prediction in the general population: the BiomarCaRE consortium.

AIMS: Our aims were to evaluate the distribution of troponin I concentrations in population cohorts across Europe, to characterize the association with cardiovascular outcomes, to determine the predictive value beyond the variables used in the ESC SCORE, to test a potentially clinically relevant cut-off value, and to evaluate the improved eligibility for statin therapy based on elevated troponin I concentrations retrospectively. METHODS AND RESULTS: Based on the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project, we analysed individual level data from 10 prospective population-based studies including 74 738 participants. We investigated the value of adding troponin I levels to conventional risk factors for prediction of cardiovascular disease by calculating measures of discrimination (C-index) and net reclassification improvement (NRI). We further tested the clinical implication of statin therapy based on troponin concentration in 12 956 individuals free of cardiovascular disease in the JUPITER study. Troponin I remained an independent predictor with a hazard ratio of 1.37 for cardiovascular mortality, 1.23 for cardiovascular disease, and 1.24 for total mortality. The addition of troponin I information to a prognostic model for cardiovascular death constructed of ESC SCORE variables increased the C-index discrimination measure by 0.007 and yielded an NRI of 0.048, whereas the addition to prognostic models for cardiovascular disease and total mortality led to lesser C-index discrimination and NRI increment. In individuals above 6 ng/L of troponin I, a concentration near the upper quintile in BiomarCaRE (5.9 ng/L) and JUPITER (5.8 ng/L), rosuvastatin therapy resulted in higher absolute risk reduction compared with individuals <6 ng/L of troponin I, whereas the relative risk reduction was similar. CONCLUSION: In individuals free of cardiovascular disease, the addition of troponin I to variables of established risk score improves prediction of cardiovascular death and cardiovascular disease.