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Introduction: Cardiovascular (CV) disease, the leading cause of death globally, is largely preventable through targeting modifiable risk factors. Scores of modifiable CV risk factors able to collect the combined effect of all the included components were mainly developed in US populations, or do not include nutritional aspects. Hypothesis: We assessed the hypothesis that an algorithm for measuring the global impact of nine modifiable CV risk factors, including dietary factors is useful in a Mediterranean population. Methods: Data on 16 656 participants of the Moli-sani Study (age ≥45y, 47% men), Italy, were used. The Moli-sani Risk Score (MRS) was calculated as a weighted sum of smoking, adherence to Mediterranean diet, LDL and HDL cholesterol, triglycerides, blood pressure, glucose, physical activity and relative fat mass. A composite outcome of fatal or non-fatal CV events was used. The Risk-and-Prevention Study, Italy (N=8606) acted as external validation cohort and the Life's Simple 7 metric as benchmark. Results: In the derivation cohort, 816 CV events occurred in 8.1 years (median) of follow-up. In multivariable Cox analysis adjusted for non-modifiable risk factors, 1-unit increase in the MRS was associated with a hazard ratio (HR) for CV events of 1.07 (95%CI: 1.06-1.08). In comparison with individuals in the first quartile, those in the fourth quartile of the MRS had HR=3.18 (2.54-3.97, Table). In the validation cohort, individuals in the fourth quartile reported a HR=1.69 (1.39-2.05). In comparison with the Life's Simple 7 metric, the MRS performed better in the derivation cohort and similarly in the validation cohort. Conclusions: The Moli-sani Risk Score is a validated, replicable algorithm predictive of CV events, based on nine modifiable CV risk factors, well performing in a Mediterranean population. The MRS can be useful to evaluate the efficacy of preventive strategies, to design intervention schemes and to communicate effectiveness of a preventive action, increasing compliance to the strategy itself.

Summary Background Diabetes prevalence is increasing in most places in the world, but prevalence is affected by both risk of developing diabetes and survival of those with diabetes. Diabetes incidence is a better metric to understand the trends in population risk of diabetes. Using a multicountry analysis, we aimed to ascertain whether the incidence of clinically diagnosed diabetes has changed over time. Methods In this multicountry data analysis, we assembled aggregated data describing trends in diagnosed total or type 2 diabetes incidence from 24 population-based data sources in 21 countries or jurisdictions. Data were from administrative sources, health insurance records, registries, and a health survey. We modelled incidence rates with Poisson regression, using age and calendar time (1995–2018) as variables, describing the effects with restricted cubic splines with six knots for age and calendar time. Findings Our data included about 22 million diabetes diagnoses from 5 billion person-years of follow-up. Data were from 19 high-income and two middle-income countries or jurisdictions. 23 data sources had data from 2010 onwards, among which 19 had a downward or stable trend, with an annual estimated change in incidence ranging from −1·1% to −10·8%. Among the four data sources with an increasing trend from 2010 onwards, the annual estimated change ranged from 0·9% to 5·6%. The findings were robust to sensitivity analyses excluding data sources in which the data quality was lower and were consistent in analyses stratified by different diabetes definitions. Interpretation The incidence of diagnosed diabetes is stabilising or declining in many high-income countries. The reasons for the declines in the incidence of diagnosed diabetes warrant further investigation with appropriate data sources. Funding US Centers for Disease Control and Prevention, Diabetes Australia Research Program, and Victoria State Government Operational Infrastructure Support Program.

Aim To examine the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors compared with other antihyperglycaemic agents (AHAs) in large and unselected populations of the Lombardy and Apulia regions in Italy. Materials and methods An observational cohort study of first-time users of GLP-1RAs, SGLT2 inhibitors or other AHAs was conducted from 2010 to 2018. Death and cardiovascular (CV) events were evaluated using conditional Cox models in propensity-score-matched populations. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated for each region and in a meta-analysis for pooled risks. Results After propensity-score matching, the Lombardy cohort included 18 716 and 11 683 patients and the Apulia cohort 9772 and 6046 patients for the GLP-1RA and SGLT2 inhibitor groups, respectively. Use of GLP-1RAs was associated with lower rates of death (HR 0.61, CI 0.56-0.65, Lombardy; HR 0.63, CI 0.55-0.71, Apulia), cerebrovascular disease and ischaemic stroke (HR 0.70, CI 0.63-0.79; HR 0.72, CI 0.60-0.87, Lombardy), peripheral vascular disease (HR 0.72, CI 0.64-0.82, Lombardy; HR 0.80, CI 0.67-0.98, Apulia), and lower limb complications (HR 0.67, CI 0.56-0.81, Lombardy; HR 0.69, CI 0.51-0.93, Apulia). Compared with other AHAs, SGLT2 inhibitor use decreased the risk of death (HR 0.47, CI 0.40-0.54, Lombardy; HR 0.43, CI 0.32-0.57, Apulia), cerebrovascular disease (HR 0.75, CI 0.61-0.91, Lombardy; HR 0.72, CI 0.54-0.96, Apulia), and heart failure (HR 0.56, CI 0.46-0.70, Lombardy; HR 0.57, CI 0.42-0.77, Apulia). In the pooled cohorts, a reduction in heart failure was also observed with GLP-1RAs (HR 0.89, 95% CI 0.82-0.97). Serious adverse events were quite low in frequency. Conclusion Our findings from real-world practice confirm the favourable effect of GLP-1RAs and SGLT2 inhibitors on death and CV outcomes across both regions consistently. Thus, these drug classes should be preferentially considered in a broad type 2 diabetes population beyond those with CV disease.

Although rheumatoid arthritis (RA) is associated with an increased risk of death and cardiovascular (CV) disease, the excess of these risks is expected to have diminished over time, in more recent incident cohorts with RA. We analysed the risk of all-cause death, stroke, and myocardial infarction as primary outcomes and all CV events as secondary outcomes in RA subjects compared to the general population, from 2005 to 2018. The risk outcomes were also evaluated in relation to the time since RA diagnosis. We conducted a cohort study using linkable administrative healthcare databases of the Lombardy Region, Northern Italy. Analyses included subjects newly diagnosed RA subjects and a random sample of No-RA subjects. An adjusted Cox proportional hazard regression model was used to calculate hazard ratios and 95% CIs for all outcomes. The study population comprised 16,047 RA subjects and 500,000 without RA. The risks of dying (HR 1.22, 95% CI 1.15–1.30), stroke (HR 1.39, 95% CI 1.22–1.58), myocardial infarction (HR 2.00, 95% CI 1.78–2.26) were significantly higher in the RA cohort, as were those that for secondary outcomes. Differences between RA and No-RA already emerged during the first five years after diagnosis. Risk patterns remained statistically significant during the next 5 years or more. Subjects with RA still have a higher risk of death and worse CV outcomes than the general population, appearing early and not decreasing with time. Preventive interventions are urgently needed.

AIM Insulin is the preferred treatment for the control of diabetes in hospital, but it raises the risk of hypoglycaemia, often because oral intake of carbohydrates in hospitalized persons is lower than planned. Our aim was to assess the effect on the incidence of hypoglycaemia of giving prandial insulin immediately after a meal depending on the amount of carbohydrate ingested. METHODS A prospective pre-post intervention study in hospitalized persons with diabetes eating meals with stable doses of carbohydrates present in a few fixed foods. Foods were easily identifiable on the tray and contained fixed doses of carbohydrates that were easily quantifiable by nurses as multiples of 10 g (a 'brick'). Prandial insulin was given immediately after meals in proportion to the amount of carbohydrates eaten. RESULTS In 83 of the first 100 people treated with the 'brick diet', the oral carbohydrate intake was lower than planned on at least one occasion (median: 3 times; Q1-Q3: 2-6 times) over a median of 5 days. Compared with the last 100 people treated with standard procedures, postprandial insulin given on the basis of ingested carbohydrate significantly reduced the incidence of hypoglycaemic events per day, from 0.11 ± 0.03 to 0.04 ± 0.02 (P

Aim: To compare the association of metformin use and coronavirus disease 2019 (COVID-19) outcomes in a cohort of 31 966 patients with diabetes in Lombardy. Methods: We used a COVID-19 linkable administrative regional database to select patients with diabetes who were aged 40 years or older. They had at least two prescriptions of antidiabetic drugs in 2019 and a positive test for severe acute respiratory syndrome coronavirus-2 from 15 February 2020 to 15 March 2021. The association of metformin use and clinical outcomes was assessed by multivariable logistic regression analyses and after propensity score matching (PSM). Clinical outcomes were all-cause mortality, in-hospital mortality, hospitalization for COVID-19, and admission to an intensive care unit (ICU). Results: In multivariable models, metformin use was associated with a significantly lower risk of total mortality (OR 0.70; 95% CI 0.66-0.75), in-hospital mortality (OR 0.68; 95% CI 0.63-0.73), hospitalization for COVID-19 (OR 0.86; 95% CI 0.81-0.91), and ICU admission (OR 0.81; 95% CI 0.69-0.94) compared with metformin non-users. Results were similar after PSM; metformin was associated with a significantly lower risk of total mortality (OR 0.79; 95% CI 0.73-0.86), in-hospital mortality (OR 0.74; 95% CI 0.67-0.81), and ICU admission (OR 0.77; 95% CI 0.63-0.95). Conclusions: In this large cohort, metformin use was associated with a protective effect in COVID-19 clinical outcomes, suggesting that it might be a potentially useful drug to prevent severe COVID-19 disease, although randomized controlled trials (RCTs) are needed to confirm this. While awaiting the results of RCTs, we suggest continuing prescribing metformin to COVID-19 patients with diabetes.

BACKGROUND: Diabetes is a major public health issue. Because lifetime risk, life expectancy, and years of life lost are meaningful metrics for clinical decision making, we aimed to estimate these measures for type 2 diabetes in the high-income setting.; METHODS: For this multinational, population-based study, we sourced data from 24 databases for 23 jurisdictions (either whole countries or regions of a country): Australia; Austria; Canada; Denmark; Finland; France; Germany; Hong Kong; Hungary; Israel; Italy; Japan; Latvia; Lithuania; the Netherlands; Norway; Scotland; Singapore; South Korea; Spain; Taiwan; the UK; and the USA. Our main outcomes were lifetime risk of type 2 diabetes, life expectancy in people with and without type 2 diabetes, and years of life lost to type 2 diabetes. We modelled the incidence and mortality of type 2 diabetes in people with and without type 2 diabetes in sex-stratified, age-adjusted, and calendar year-adjusted Poisson models for each jurisdiction. Using incidence and mortality, we constructed life tables for people of both sexes aged 20-100 years for each jurisdiction and at two timepoints 5 years apart in the period 2005-19 where possible. Life expectancy from a given age was computed as the area under the survival curves and lifetime lost was calculated as the difference between the expected lifetime of people with versus without type 2 diabetes at a given age. Lifetime risk was calculated as the proportion of each cohort who developed type 2 diabetes between the ages of 20 years and 100 years. We estimated 95% CIs using parametric bootstrapping.; FINDINGS: Across all study cohorts from the 23 jurisdictions (total person-years 1577234194), there were 5119585 incident cases of type 2 diabetes, 4007064 deaths in those with type 2 diabetes, and 11854043 deaths in those without type 2 diabetes. The lifetime risk of type 2 diabetes ranged from 16·3% (95% CI 15·6-17·0) for Scottish women to 59·6% (58·5-60·8) for Singaporean men. Lifetime risk declined with time in 11 of the 15 jurisdictions for which two timepoints were studied. Among people with type 2 diabetes, the highest life expectancies were found for both sexes in Japan in 2017-18, where life expectancy at age 20 years was 59·2 years (95% CI 59·2-59·3) for men and 64·1 years (64·0-64·2) for women. The lowest life expectancy at age 20 years with type 2 diabetes was observed in 2013-14 in Lithuania (43·7 years [42·7-44·6]) for men and in 2010-11 in Latvia (54·2 years [53·4-54·9]) for women. Life expectancy in people with type 2 diabetes increased with time for both sexes in all jurisdictions, except for Spain and Scotland. The life expectancy gap between those with and without type 2 diabetes declined substantially in Latvia from 2010-11 to 2015-16 and in the USA from 2009-10 to 2014-15. Years of life lost to type 2 diabetes ranged from 2·5 years (Latvia; 2015-16) to 12·9 years (Israel Clalit Health Services; 2015-16) for 20-year-old men and from 3·1 years (Finland; 2011-12) to 11·2 years (Israel Clalit Health Services; 2010-11 and 2015-16) for 20-year-old women. With time, the expected number of years of life lost to type 2 diabetes decreased in some jurisdictions and increased in others. The greatest decrease in years of life lost to type 2 diabetes occurred in the USA between 2009-10 and 2014-15 for 20-year-old men (a decrease of 2·7 years).; INTERPRETATION: Despite declining lifetime risk and improvements in life expectancy for those with type 2 diabetes in many high-income jurisdictions, the burden of type 2 diabetes remains substantial. Public health strategies might benefit from tailored approaches to continue to improve health outcomes for people with diabetes.; FUNDING: US Centers for Disease Control and Prevention and Diabetes Australia. Copyright © 2022 Elsevier Ltd. All rights reserved.

Population-level trends in mortality among people with diabetes are inadequately described. We aimed to examine the magnitude and trends in excess all-cause mortality in people with diabetes.In this retrospective, multicountry analysis, we collected aggregate data from 19 data sources in 16 high-income countries or jurisdictions (in six data sources in Asia, eight in Europe, one from Australia, and four from North America) for the period from Jan 1, 1995, to Dec 31, 2016, (or a subset of this period) on all-cause mortality in people with diagnosed total or type 2 diabetes. We collected data from administrative sources, health insurance records, registries, and a health survey. We estimated excess mortality using the standardised mortality ratio (SMR).In our dataset, there were approximately 21 million deaths during 0·5 billion person-years of follow-up among people with diagnosed diabetes. 17 of 19 data sources showed decreases in the age-standardised and sex-standardised mortality in people with diabetes, among which the annual percentage change in mortality ranged from -0·5% (95% CI -0·7 to -0·3) in Hungary to -4·2% (-4·3 to -4·1) in Hong Kong. The largest decreases in mortality were observed in east and southeast Asia, with a change of -4·2% (95% CI -4·3 to -4·1) in Hong Kong, -4·0% (-4·8 to -3·2) in South Korea, -3·5% (-4·0 to -3·0) in Taiwan, and -3·6% (-4·2 to -2·9) in Singapore. The annual estimated change in SMR between people with and without diabetes ranged from -3·0% (95% CI -3·0 to -2·9; US Medicare) to 1·6% (1·4 to 1·7; Lombardy, Italy). Among the 17 data sources with decreasing mortality among people with diabetes, we found a significant SMR increase in five data sources, no significant SMR change in four data sources, and a significant SMR decrease in eight data sources.All-cause mortality in diabetes has decreased in most of the high-income countries we assessed. In eight of 19 data sources analysed, mortality decreased more rapidly in people with diabetes than in those without diabetes. Further longevity gains will require continued improvement in prevention and management of diabetes.US Centers for Disease Control and Prevention, Diabetes Australia Research Program, and Victoria State Government Operational Infrastructure Support Program.

Background: High concentrations of ivermectin demonstrated antiviral activity against SARS-CoV-2 in vitro. Aim of this study was to assess safety and efficacy of high-dose ivermectin in reducing viral load in individuals with initial SARS-CoV-2 infection. Methods: Randomised, double-blind, multicentre, phase II, dose-finding, proof-of-concept clinical trial performed in outpatients in Italy. Participants: adults recently diagnosed with asymptomatic/oligosymptomatic SARS-CoV-2 infection, providing informed consent. Exclusion criteria: pregnant or lactating women; CNS diseases; participants under dialysis; severe medical condition with prognosis < 6 months; warfarin treatment; antiviral/chloroquine phosphate/hydroxychloroquine treatment. Participants were assigned according to a randomized permuted block procedure to one of the following arms with allocation ratio 1:1:1: placebo (arm A); single dose ivermectin 600 μg/kg plus placebo for 5 days (arm B); single dose ivermectin 1200 μg/kg for 5 days (arm C). The pharmacist prepared the treatment according to the randomization list and on the basis of the participant’s weight. Primary outcomes: serious adverse drug reactions (SADR) and change of viral load at Day 7. The protocol was registered with ClinicalTrials.gov , NCT04438850. Findings. From 31th July, 2020 to 26th May, 2021, 32 participants were randomized to arm A, 29 to arm B and 32 to arm C. The recruitment was stopped on 10th June, because of a dramatic drop of cases. Eighty-nine participants were included in the safety analysis set, the change in viral load was calculated on 87 participants. No SADR were registered. The mean log10 viral load reduction was 2.9 in arm C (SD 1.6), 2.5 (2.2) in arm B and 2.0 (2.1) in arm A, with no significant differences (p=0.099 and 0.122 for C versus A and B versus A, respectively). Interpretation: High- dose ivermectin demonstrated safe, but did not prove efficacy to reduce viral load. Trial Registration: The protocol was registered with ClinicalTrials.gov , NCT04438850. Funding: The trial was partly funded by the Italian Ministry of Health. Declaration of Interest: None to declare. Ethical Approval: This study was approved by the national Ethics Committee of INMI – Spallanzani in Rome that is competent for all COVID-19 trials in Italy (resolution 139/2020 of 28th May, 2020), and by the Italian drug agency AIFA (resolution 136BIS/2020 of 18th May, 2020).

Aims Data on the impact of liver disease (LD) in patients with atrial fibrillation (AF) and the role of oral anticoagulant (OAC) drugs for stroke prevention, are limited. We analysed the impact of LD and OAC treatment in determining stroke, major bleeding, all-cause death and secondary bleeding outcomes. Methods A retrospective observational population-based cohort study. The study cohort is derived from the administrative health databases of Lombardy region (>10 million inhabitants), Italy. All AF patients ≥40 years admitted to hospital from 2000 to 2018 were considered. AF and LD diagnosis were established using ICD9-CM codes. Use of OAC was determined with Anatomical Therapeutic Chemical (ATC) codes. Primary study outcomes were stroke, major bleeding and all-cause death. Results Among 393,507 AF patients, 16,168 (4.1%) had concomitant LD. LD AF patients were significantly less treated with OAC independent of associated clinical characteristics (OR: 0.96, 95% CI: 0.92–0.98). Concomitant LD was found associated with an increased risk in all the study outcomes (HR: 1.18, 95% CI: 1.11–1.25 for stroke; HR: 1.57, 95% CI: 1.47–1.66 for major bleeding; HR: 1.41, 95% CI: 1.39–1.44 for all-cause death. Use of OAC in patients with AF and LD resulted in a reduction in stroke (HR: 0.80, 95% CI: 0.70–0.92), major bleeding (HR: 0.86, 95% CI: 0.74–0.99) and all-cause death (HR: 0.85, 95% CI: 0.80–0.90), with similar results according to several clinically relevant subgroups. A net clinical benefit (NCB) analysis suggested a positive benefit/risk ratio in using OAC in AF patients with LD (NCB: 0.408, 95% CI: 0.375–0.472). Conclusions In AF patients, concomitant LD carries a significantly higher risk for all clinical outcomes. Use of OAC in AF patients with LD was associated with a significant benefit/risk ratio, even in high-risk patient subgroups. Funding Acknowledgement Type of funding source: None

Background:GLP-1 receptor agonists (G LP-1 RA) and SGLT-2 inhibitors (SGLT-2i) are recommended in type 2 diabetes subjects with established cardiovascular (CV) disease or at high CV risk. The efficacy and safety of GLP-1 RA and SGLT-2i compared with other anti-hyperglycemic agents (AHAs) was examined in large unselected populations of Lombardy and Apulia regions in Italy.Methods:An observational cohort study of new users of GLP-1 RA, SGLT-2i and other AHAs was conducted from 2010 to 2018. Death and cardiovascular events were evaluated using conditional Cox models in propensity-score matched populations. Adjusted hazard ratios (95%, CI) were calculated for each region and as meta-analysis for pooled risks.Results:After propensity-matching, the Lombardy cohort included 18,716 and 11,683 pairs and the Apulia cohort 9,772 and 6,046 pairs for the GLP-1 RA and SGLT-2i groups, respectively. Use of GLP-1 RA was associated with lower rates of death (HR 0.61, CI 0.56-0.65, Lombardy; HR 0.63, CI 0.55-0.71, Apulia), cerebrovascular disease and ischemic stroke (HR 0.70, CI 0.63-0.79; HR 0.72, CI 0.60-0.87, Lombardy) peripheral vascular disease (HR 0.72, CI 0.64-0.82, Lombardy; HR 0.80, CI 0.67-0.98, Apulia) and, lower limb complications (HR 0.67, CI 0.56-0.81, Lombardy; HR 0.69, CI 0.51-0.93, Apulia). Compared to other AHAs, SGLT-2i use decreased the risk of death (HR 0.47, CI 0.40-0.54, Lombardy; HR 0.43, CI 0.32-0.57, Apulia), cerebrovascular disease (HR 0.75, CI 0.61-0.91, Lombardy, HR 0.72, CI 0.54-0.96, Apulia), and heart failure (HR 0.56, CI 0.46-0.70, Lombardy, HR 0.57, CI 0.42-0.77, Apulia). In the pooled cohorts, a reduction in heart failure was also observed with GLP-1 RA (HR 0.89, 95% CI 0.82-0.97). Serious adverse events were quite low in frequency. Conclusions: Our findings from real world practice confirm the favorable effect of GLP-1 RA and SGLT-2i on death and CV outcomes consistent across both regions. Thus, these drug classes should be preferentially considered in a broad type 2 diabetes population beyond subjects with CV disease.

Although rheumatoid arthritis (RA) is associated with an increased risk of death and cardiovascular (CV) disease, the excess of these risks is expected to have diminished over time, in more recent incident cohorts with RA. We analysed the risk of all-cause death, stroke, and myocardial infarction as primary outcomes and all CV events as secondary outcomes in RA subjects compared to the general population, from 2005 to 2018. The risk outcomes were also evaluated in relation to the time since RA diagnosis. We conducted a cohort study using linkable administrative healthcare databases of the Lombardy Region, Northern Italy. Analyses included subjects newly diagnosed RA subjects and a random sample of No-RA subjects. An adjusted Cox proportional hazard regression model was used to calculate hazard ratios and 95% CIs for all outcomes. The study population comprised 16,047 RA subjects and 500,000 without RA. The risks of dying (HR 1.22, 95% CI 1.15-1.30), stroke (HR 1.39, 95% CI 1.22-1.58), myocardial infarction (HR 2.00, 95% CI 1.78-2.26) were significantly higher in the RA cohort, as were those that for secondary outcomes. Differences between RA and No-RA already emerged during the first five years after diagnosis. Risk patterns remained statistically significant during the next 5 years or more. Subjects with RA still have a higher risk of death and worse CV outcomes than the general population, appearing early and not decreasing with time. Preventive interventions are urgently needed.

Background: In contrast with the abundance of global epidemiological descriptive data on cardiovascular diseases and their risk factors, information on the outcomes of real populations prospectively followed up in their life and care settings is much rarer, especially in low-income countries.Objectives: This study sought to evaluate the feasibility and the overall results of a hypertension control program, based mainly on a network of community nonprofessional health promoters, in the poor rural region of Borbon (Ecuador).Methods: This is a prospective cohort study describing the results of a program of hypertension diagnosis, treatment and follow-up from 2004 to 2015 in the area, carried out mainly by the health promoters.Results: The number of hypertensive patients identified and followed over the years increased from 1,024 in 2004 to 1,733 in 2015. The percentage of patients with no visits during a year was reduced to

Background The aim of our study was to evaluate whether treatments for peripheral artery disease changed in two different cohorts identified in 2002 and 2008, and whether this had an impact on mortality and major clinical outcomes after six years of follow-up. Methods Using administrative health databases of the largest region in Northern Italy, we identified patients admitted to hospital for peripheral artery disease in 2002 and 2008. Both cohorts were followed for six years. All cause death, acute coronary syndrome, stroke and major amputations, cardiovascular prevention drugs and revascularization procedures were collected. Incidence of events was plotted using adjusted cumulative incidence function estimates. The risk, for each outcome, was compared between 2002–2008 and 2008–2014 using a multivariable Fine and Gray’s semiparametric proportional subdistribution hazards model. Results In 2002 and 2008, 2885 and 2848 patients were identified. Adjusting for age, sex, Charlson comorbidity index and severity of peripheral artery disease we observed a significant reduction (in 2008 vs. 2002) in the risk of acute coronary syndrome (28%), stroke (27%) and major amputation (17%). No change was observed in the risk of death. The percentages of patients with peripheral artery revascularizations, during the hospital stay, increased: 43.8% in 2002 vs. 49.0% in 2008, p Conclusions In six years of follow-up we observed a reduction in risk of major cardiovascular events in 2008–2014 in comparison with the 2002–2008 cohort. Increasing use of revascularization interventions and cardiovascular prevention drugs could have contributed to the better prognosis.

Background The clinical benefit of aspirin for the primary prevention of cardiovascular disease (CVD) in diabetes remains uncertain. To evaluate the efficacy and safety of aspirin for the primary prevention of cardiovascular outcomes and all-cause mortality events in people with diabetes, we conducted an updated meta-analysis of published randomised controlled trials (RCTs) and a pooled analysis of individual participant data (IPD) from three trials. Methods Randomised controlled trials of aspirin compared with placebo (or no treatment) in participants with diabetes with no known CVD were identified from MEDLINE, Embase, Cochrane Library, and manual search of bibliographies to January 2019. Relative risks with 95% confidence intervals were used as the summary measures of associations. Results We included 12 RCTs based on 34,227 participants with a median treatment duration of 5.0 years. Comparing aspirin use with no aspirin, there was a significant reduction in risk of major adverse cardiovascular events (MACE)0.89 (0.83–0.95), with a number needed to treat (NNT)of 95 (95% CI 61 to 208) to prevent one MACE over 5 years average follow-up. Evidence was lacking of heterogeneity and publication bias among contributing trials for MACE. Aspirin use had no effect on other endpoints including all-cause mortality; however, there was a significant reduction in stroke for aspirin dosage ≤ 100 mg/day 0.75 (0.59–0.95). There were no significant effects of aspirin use on major bleeding and other bleeding events, though some of the estimates were imprecise. Pooled IPD from the three trials (2306 participants) showed no significant evidence of an effect of aspirin on any of the outcomes evaluated; however, aspirin reduced the risk of MACE in non-smokers 0.70 (0.51–0.96) with a NNT of 33 (95% CI 20 to 246) to prevent one MACE. Conclusions Aspirin has potential benefits in cardiovascular primary prevention in diabetes. The use of low dose aspirin may need to be individualised and based on each individual’s baseline CVD and bleeding risk. Systematic review registration PROSPERO: CRD42019122326

To analyze sex-related differences about AF prevalence, use of OAC and outcomes focusing on the older age classes. We used administrative data of the Lombardy Region, describing period prevalence, use of OAC and outcomes from 2002 to 2014 for all patients diagnosed with AF. AF prevalence over the 2002–2014 period was higher in males than in females (2.7% vs. 2.1%, p

Objectives: To analyze the relationship between atrial fibrillation (AF) and Charlson comorbidity index (CCI) in a population-based cohort study over a long-term follow-up period, in relation to oral anticoagulant (OAC) prescriptions and outcomes. Patients and Methods: We used data from the administrative health databases of Lombardy. All patients with AF and age 40 years and older and who were admitted to the hospital in 2002 were considered for analysis and followed up to 2014. AF diagnosis and CCI were established according to codes from the International Classification of Diseases, Ninth Revision. Results: In 2002, 24,040 patients were admitted with a diagnosis of AF. CCI was higher in patients with AF than in those without AF (1.8±2.1 vs 0.2±0.9; P

Aims Heart failure (HF) and chronic obstructive pulmonary disease (COPD) frequently co-exist, and each is a major public health issue. In a large cohort of hospitalized HF patients, we evaluated: (i) the impact of COPD on clinical outcomes; (ii) whether outcomes and treatments changed from 2002 to 2009; and (iii) the relationship between outcomes and treatments focusing on beta-blockers (BBs) and bronchodilators (BDs). Methods and results From linkable Lombardy administrative health databases, we selected individuals with a discharge diagnosis of HF with or without concomitant COPD (HF yesCOPD and HF noCOPD) in 2002 and 2009. Patients were followed up for 4 years. Outcomes were total mortality, first readmission for HF, and their combination. Unadjusted and adjusted Cox proportional models and competing risk analyses were used. We identified 11 274 patients with HF noCOPD and 2837 with HF yesCOPD. HF yesCOPD patients in 2002 and 2009 had a 20% higher risk of the outcomes. From 2002 to 2009, BB and BD prescriptions increased significantly. In HF noCOPD patients, risks for mortality [adjusted hazard ratio (HR) 0.91, 95% confidence interval (CI) 0.86–0.97], first HF readmission (HR 0.79, 95% CI 0.74–0.85), and the combined endpoint (HR 0.88, 95% CI 0.84–0.92) declined (all P < 0.003) while in HF yesCOPD only the risk for first HF readmission dropped (HR 0.86, 95% CI 0.76–0.97; P = 0.018). BBs were associated with significantly lower mortality in both groups, but with a higher risk for first HF readmission in HF noCOPD. Outcomes did not significantly differ in HF yesCOPD treated or not with BDs. Conclusions The prognosis of patients hospitalized for HF, either with or without COPD, seemed to improve between 2002 and 2009, with possibly better survival of those on BBs. Because of residual confounding in observational studies, a randomized controlled trial should be considered to confirm these results.

To assess the pattern of use of Emergency Departments (EDs), factors contributing to the visits, geographical distribution and outcomes in people aged 65 years or more living in the Italian Lombardy Region in 2012. Based on an administrative database the study population was divided into groups according to the number of ED visits. A multinomial logistic regression model was performed to compare the characteristics of each group. The Getis–Ord’s G statistic was used to evaluate the clusters of high and low visit prevalence odd ratios (OR) at district level. To estimate the severity of the disease leading to ED attendance, visits were stratified based on the level of emergency and outcome. About 2 million older people were included in the analyses: 78 % had no ED visit, 15 % only 1, 7 % 2 or more. Male sex, age 85 years or more, high number of drugs, ED visits and hospital admissions in the previous year and the location of an ED within 10 km from the patient’s place were all factors associated with a higher risk to have more ED visits. Clusters of high and low prevalence of visits were found for occasional users. Overall, 83 % of ED visit with a low emergency triage code at admission had as visit outcome discharge at home. In older people several variables were associated with an increased risk to have a high number of ED visits. Most of the visits were done for non-urgent problems and significant geographic differences were observed for occasional users.

Background Atrial fibrillation (AF) is the most commonly diagnosed arrhythmia, which is associated with an increased risk of stroke. Several studies have suggested that female AF patients could have a greater risk for stroke and thromboembolic events (TE). Methods A systematic literature review update and meta-analysis was conducted using Pubmed. The search used the terms "atrial fibrillation", "gender", "sex", "female", "women", "stroke", "thromboembolism". Main aim of the study was to compare and male AF patients for occurrence of stroke and TE. Secondary outcomes were: major bleeding, cardiovascular (CV) death and all-cause death. Results Forty-four studies were included in the analysis including 993,603 patients (48.9% women). After pooling the data, there was a higher risk of stroke for women vs. male AF patients (hazard ratio [HR]: 1.24; 95% confidence intervals [CIs]: 1.14–1.36). Overall, TE risk was not different between female and male patients, despite sensitivity analysis left some uncertainties. No sex differences were found for major bleeding, CV death and all-cause death. A significant relationship between increasing age and the difference in stroke risk between female and male AF patients was found (Delta HR: 1.01; 95% CI: 1.00–1.03 for each year of age increase). Conclusions Female patients with AF are at increased risk of stroke compared to men. A significant relationship between increasing age and stroke risk in women compared to men was found, most evident at age > 65 years. Female sex may act as a stroke risk modifier, particularly in elderly and very elderly AF subjects, conferring a significant increase in stroke risk.

A one-dose-fits-all approach to use of aspirin has yielded only modest benefits in long-term prevention of cardiovascular events, possibly due to underdosing in patients of large body size and excess dosing in patients of small body size, which might also affect other outcomes.Using individual patient data, we analysed the modifying effects of bodyweight (10 kg bands) and height (10 cm bands) on the effects of low doses (≤100 mg) and higher doses (300-325 mg or ≥500 mg) of aspirin in randomised trials of aspirin in primary prevention of cardiovascular events. We stratified the findings by age, sex, and vascular risk factors, and validated them in trials of aspirin in secondary prevention of stroke. Additionally, we assessed whether any weight or height dependence was evident for the effect of aspirin on 20-year risk of colorectal cancer or any in-trial cancer.Among ten eligible trials of aspirin in primary prevention (including 117 279 participants), bodyweight varied four-fold and trial median weight ranged from 60·0 kg to 81·2 kg (p0·0001). The ability of 75-100 mg aspirin to reduce cardiovascular events decreased with increasing weight (pLow doses of aspirin (75-100 mg) were only effective in preventing vascular events in patients weighing less than 70 kg, and had no benefit in the 80% of men and nearly 50% of all women weighing 70 kg or more. By contrast, higher doses of aspirin were only effective in patients weighing 70 kg or more. Given that aspirin's effects on other outcomes, including cancer, also showed interactions with body size, a one-dose-fits-all approach to aspirin is unlikely to be optimal, and a more tailored strategy is required.Wellcome Trust and National Institute for Health Research Oxford Biomedical Research Centre.

Diabetes mellitus (DM) and atrial fibrillation (AF) are worldwide public health challenges and major causes of death and cardiovascular events. The association between DM and AF is controversial in literature and data on outcomes of individuals with both diseases have not been evaluated in population studies. We tested the hypothesis that DM is independently associated to AF hospitalization and assessed the risk of stroke and mortality in people with both conditions.We conducted a population-based cohort-study of DM patients and their corresponding controls identified in a administrative health database of the Lombardy Region. Both cohorts were followed for nine years. A multivariable Cox proportional-hazards-regression model was used to estimate the hazard ratio (HR) for first hospitalization for AF and for clinical outcomes.Out of 9,061,258 residents, 285,428 (3.14%) DM subjects were identified, mean age 65.8±15 years, 49% were women. The cumulative incidence of AF in DM was 10.4% vs. 7.4% in non-DM. DM was a risk factor for AF (HR 1.32, 95% CI 1.30-1.34; p0.0001). Oral anticoagulants were prescribed in 34.8% of DM patients with AF. DM associated with AF, presented the highest HR for stroke: 2.63; 95% CI 2.47-2.80 and for total death, HR 2.41; 95% CI 2.36-2.47.In this population study, DM was an independent risk factor for AF hospitalization. DM patients with AF had the highest risk of stroke and total mortality. Early identification of AF and a structured plan to optimize the comprehensive management of DM and AF patients is mandatory.

To describe the incidence of ischemic stroke, short-term mortality, recurrences, and prescription patterns.Data from administrative health databases of the Lombardy Region from 2002 to 2010 (about 4 million people) were analyzed for stroke incidence and recurrence, mortality, and drug prescriptions after an ischemic stroke.A total of 43,352 patients with a first hospital admission for ischemic stroke were identified. During 8 years, stroke incidence decreased from 3.2 of 1000 to 2.4 of 1000 (P.001) in people aged 65-74 years, from 7.1 of 1000 to 5.3 of 1000 (P.001) at ages 75-84 years and from 11.9 of 1000 to 9.4 of 1000 (P.001) at age 85 years or older. Stroke recurrences dropped by 30% (from 10.0% to 7.0%, P.001) and 30-day mortality rate also decreased. Prescription trends showed linear increase in antiplatelets and lipid-lowering drugs, respectively, from 60.2% to 65.0% (P.001) and from 19.1% to 34.6% (P.001), whereas antihypertensive prescriptions did not change appreciably. Anticoagulant prescription increased in patients with atrial fibrillation, from 64.8% to 72.1% in the 65-74 years age group, (P = .004) and from 40.2% to 53.7% in the 75-84 years age group (P.001); less than 20% of the 85 years or older age group were treated with anticoagulants (P.0001).Stroke incidence, recurrence, and 30-day mortality decreased from 2002 to 2010 concomitant with an increase in prescriptions of secondary stroke prevention drugs.

To assess the effectiveness, safety and feasibility of the revised, simplified nurse-managed version of our insulin infusion protocol, adapted to the new recommended glycaemic target of 140 to 180 mg/dL (Desio Diabetes Diagram i.v. 140-180).All clinical responses to the Desio Diabetes Diagram i.v. 140-180 in use for 3 years were recorded in patients with diabetes or hyperglycaemia admitted to our intensive cardiac care unit. To assess the feasibility, we asked nurses to complete an ad hoc questionnaire anonymously when the new insulin infusion protocol had been in use for 2 years.From December 2010 to December 2013, 276 patients (173 men, median age 75 years) were treated according to the Desio Diabetes Diagram i.v. 140-180. The median time to reach glycaemic target was 4 h (Q1-Q3 2-8) in 128 patients with blood glucose180 mg/dL and 2 h (Q1-Q3 1-4) in 82 patients with blood glucose140 mg/dL. Once the target had been reached, insulin infusion was maintained for a median of 38 h (Q1-Q3 24-48) with blood glucose between 140 and 180 mg/dL for 58.3% of the infusion time. Over a total of 11,863 h of infusion, seven blood glucose70 mg/dL occurred. The Desio Diabetes Diagram i.v. 140-180 protocol was considered easy to use by 93% of nurses.The Desio Diabetes Diagram i.v. 140-180 protocol, fully managed by nurses, with insulin and glucose intravenous infusion proved effective, safe and feasible in maintaining blood glucose between 140 and 180 mg/dL in patients with diabetes or hyperglycaemia admitted to the intensive cardiac care unit for acute cardiac events.

To compare the utilization of health care resources (drug prescriptions, hospital admissions and health care services) by immigrant versus native elderly people (65 years or more), by using administrative database of the Lombardy Region. For each immigrant (an older people born out of Italy), one person born in Lombardy (native) was randomly selected and matched by age, sex and general practitioner. The 25,508 immigrants selected were less prescribed with at least one drug (OR 0.72, 95 % CI 0.67-0.76) and had a lesser use of health care services (OR 0.79, 95 % CI 0.75-0.84) than natives. No statistically significant differences were found for hospital admission rates (OR 0.99, 95 % CI 0.99-1.04). A lower rate of health care resource utilization was observed in elderly immigrants who had been living in the host region for as many as 10 years.

To describe the prevalence and management of diabetes among immigrants according to ethnic group and duration of stay, compared to Italian citizens. Diabetic immigrant and Italian residents aged 20–69 years in the administrative database of the Lombardy Region. Immigrants were classified by region of origin and as long-term residents (LTR) and short-term residents (STR). Age- and sex-adjusted prevalence and indicators of diabetes management were calculated for immigrants by region of origin and by length of stay using Cox proportional models. In 2010 19,992 immigrants (mean age 49.1 ± 10.8, 53.7% males) and 195,049 Italians (mean age 58.7 ± 9.3, 61.1 males) with diabetes were identified. Immigrants had a higher adjusted diabetes prevalence than Italians (OR 1.48; 95% CI 1.45–1.50). STR received significantly fewer recommended cardiovascular drugs (antiplatelets, statins and ACE-inhibitors/ARBs) than Italians, although prescription was higher among LTR from some ethnic groups. Immigrants were less likely to be seen by a diabetologist and to do at least one HbA1c test per year. Although the recommended tests/visits were more often done for the LTR than the STR, in the majority of ethnic groups these indicators were still far from optimal. The prevalence and management of diabetes differ between immigrants and Italians, although some improvement can be seen among LTR.

To evaluate the association between diabetes mellitus (DM) and risk of seizures in a well-defined elderly population. The administrative databases of the Lombardy region (a 10 million population area in Northern Italy) were used to identify persons aged 65 years or older with DM (defined by prescription of antidiabetic drugs and/or through ICD-9 CM code and/or exemption code for diabetes) during the year 2002. Seizure-free DM subjects were followed until 2012 in search of individuals with incident seizures (identified through ICD-9 CM codes for epilepsy/seizures or ATC codes for antiepileptic drugs associated with the prescription of an electroencephalogram). To adjust for confounding, comorbidities having epileptogenic potential were also identified through the ICD-9 CM codes. The population at risk included 1,494,071 persons. Of these, 136,941 seizure-free patients had DM. At the end of follow-up, the cumulative time-dependent incidence of seizures was 3.0% in DM patients and 1.9% in No-diabetic individuals (hazard ratio, HR 1.47; 95% confidence interval, 1.41–1.53, adjusted for age classes, sex, comorbidities and number of hospital admission). The HR was unchanged in patients with no history of stroke. The cumulative incidence of seizures after DM increased with the number of hospital admissions. DM is an independent risk factor for seizures in elderly individuals. In diabetic patients, the risk of seizures increases with the number of comorbidities, supporting the role of vascular disease as a cause of seizures.

To describe prescribing patterns in elderly Italian diabetic patients of the Lombardy Region in 2000 and 2010 using an administrative database. Hospital admissions and mortality were also recorded and compared in the two index years.Analyses were performed on the whole cohort of elderly diabetic patients and across age groups. Direct age standardization was done, with data from the Lombardy Region database for 2005 used as reference to compare diabetic populations in the two index years. Logistic regression models were used to analyze changes in hospital admissions and mortality and to calculate odds ratios.Using data retrieved from the Lombardy Region database we identified 176,384 and 283,982 elderly diabetic patients in 2000 and 2010, respectively. The overall rates of patients treated with antidiabetic drugs were 92.5% in 2000 and 97.0% in 2010. Between 2000 and 2010 the prescribing of glibenclamide declined by 30.0% (from 52.9 to 22.9%, p 0.001) and that of biguanides rose by 17.4 % (from 47.5 to 64.8%, p 0.001). In 2010 thiazolidinediones, dipeptidyl peptidase-4 inhibitors and incretin mimetic drugs were seldom prescribed. Drugs for cardiovascular prevention rose in all age classes from 2000 to 2010, and the rates of hospital admission overall fell from 32.0 to 26.8% (p 0.001) during the same period, with the exception of those aged ≥85 years. Between 2000 and 2010 the mortality rate decreased in patients aged 65-74 years (from 3.4 to 2.9%, p 0.0001) and rose significantly in those aged ≥85 years.The drug prescription profile of elderly diabetic patients changed from 2000 to 2010, with a tendency toward recommended drugs. These changes may possibly be linked to the decrease in both hospital admissions and mortality in the diabetic group aged 65-74 years.

BACKGROUND AND AIMS: In contrast to the well-documented global prevalence of diabetes, much less is known about the epidemiology of cardiovascular (CV) complications in recent years. We describe the incidence of major CV events, deaths and drug prescribing patterns from 2002 to 2012 in subjects with (DM) or without diabetes mellitus (No DM). METHODS AND RESULTS: Subjects and outcomes were identified using linkable health administrative databases of Lombardy, a region in Northern Italy. A logistic regression model was used to compare myocardial infarction (MI), stroke, major amputation and death between DM and No DM in 2002 and 2012 and between the two index years in each population. The interaction between years and diabetes was introduced in the model. From 2002 to 2012 the incidence of major CV complications and death fell in both groups with a larger reduction among DM only for CV events: OR (95% CI) for the interaction 0.86 (0.79-0.93) for MI, 0.89 (0.82-0.96) for stroke, 0.78 (0.57-1.06) for major amputations. CV prevention drugs rose considerably from 2002 to 2012 particularly in DM and a switch towards safer antihyperglycemic drugs was also observed. CONCLUSIONS: Major CV complications and death declined from 2002 to 2012 in both DM and No DM. This might be due to a larger increase in prescriptions of CV drugs in DM and a relevant change toward recommended antihyperglycemic drugs. Background and aims In contrast to the well-documented global prevalence of diabetes, much less is known about the epidemiology of cardiovascular (CV) complications in recent years. We describe the incidence of major CV events, deaths and drug prescribing patterns from 2002 to 2012 in subjects with (DM) or without diabetes mellitus (No DM). Methods and results Subjects and outcomes were identified using linkable health administrative databases of Lombardy, a region in Northern Italy. A logistic regression model was used to compare myocardial infarction (MI), stroke, major amputation and death between DM and No DM in 2002 and 2012 and between the two index years in each population. The interaction between years and diabetes was introduced in the model. From 2002 to 2012 the incidence of major CV complications and death fell in both groups with a larger reduction among DM only for CV events: OR (95% CI) for the interaction 0.86 (0.79–0.93) for MI, 0.89 (0.82–0.96) for stroke, 0.78 (0.57–1.06) for major amputations. CV prevention drugs rose considerably from 2002 to 2012 particularly in DM and a switch towards safer antihyperglycemic drugs was also observed. Conclusions Major CV complications and death declined from 2002 to 2012 in both DM and No DM. This might be due to a larger increase in prescriptions of CV drugs in DM and a relevant change toward recommended antihyperglycemic drugs.

Background Previous studies have stated that atrial fibrillation (AF) is associated with a higher risk of dementia. However, none have examined the competition between death and incident dementia in patients with AF. We evaluated the risk of incident dementia in patients with AF in comparison to people without this arrhythmia, considering of the competing risk of death. Methods AF and non-AF cohorts were identified using the large administrative database of the Lombardy Region and followed for ten years. Patients with incident dementia were identified if they had an ICD 9 code referring to dementia at hospital discharge or a prescription for any anti-dementia drug. The association of AF with dementia or death was assessed with the multivariable Cox proportional-regression model, sensitivity analysis with a 1:1 propensity score matching and competing-risk analysis. Results In 2003 a total of 27,431 patients were hospitalized for AF in the Lombardy Region, while the cohort of non-AF counted 1,600,200 people. AF was associated with a higher risk of dementia (17%) and death (51%) at multivariable Cox analysis. These results were confirmed by the model fitted after propensity score matching. However, competing risk analysis found the association between AF and incident dementia was no longer significant (HR 0.99; 95% CI 0.94–1.04). Conclusions In this real-world population the association between AF and dementia was no longer statistically significant when death was considered a competing risk.

Diabet. Med. 29, 385–392 (2012) Abstract Aims To describe trends in diagnosed diabetes prevalence, incidence and mortality from 2000 to 2007 in the most heavily populated Italian region. Methods We examined the prevalence and incidence rates of Type 1 and Type 2 diabetes and yearly mortality rates among individuals with diabetes from 2000 to 2007 using an administrative health database of prescription, disease-specific exemption and hospitalization records of more than 9 million inhabitants of Lombardy. Age- and sex-specific rates were calculated and temporal trends for subjects aged ≥ 30 years were analysed. Results The crude point diabetes prevalence rose from 3.0% in 2000 to 4.2% in 2007, a 40% increase. The incidence remained stable during the study period with a rate of 4/1000 per year. Overall mortality declined from 43.2/1000 in 2001 to 40.3/1000 in 2007 (6.7% decrease) at a rate slightly higher than that of the general population (4.8% decrease). Our projection in subjects aged ≥ 30 years indicates that the prevalence will rise continuously over the next years, reaching 11.1% in 2030. Conclusions The prevalence of diabetes increased substantially between 2000 and 2007, mainly because there are more patients with a new diagnosis each year than those who die. The increase observed by 2007 almost reached the World Health Organization prediction for 2030. Our analyses suggest that the increase will continue over the next few decades. These data are important for defining the burden of diabetes in the near future, to help in planning health services and ensure proper allocation of resources.

OBJECTIVE The study objectives were 1) to assess the effectiveness and safety of a standardized protocol for the transition to subcutaneous insulin and oral feeding in diabetic or hyperglycemic patients with acute coronary syndrome (ACS) who were receiving intravenous insulin and glucose at the time of the transfer from the intensive cardiac care unit to a general ward and 2) to identify predictors of transition outcome. RESEARCH DESIGN AND METHODS This was a prospective observational study. The protocol specifies that patients receive a 100% of their daily subcutaneous insulin requirement from the first day of oral feeding, calculated from the intravenous insulin rate during the final 12 h divided into two: 50% basal and 50% prandial. RESULTS In 142 patients (93 male, 49 female, age range 47–88 years, 135 with known diabetes) the first day after transition, 44.8% of blood glucose (BG) measurements were within the strict range of 100–140 mg/dL before meals and 100–180 mg/dL after meals, and 70.8% were within the broader ranges of 80–160 mg/dL and 80–200 mg/dL, respectively. Pre- or postprandial hypoglycemia (BG CONCLUSIONS This study shows the effectiveness and safety of a standardized protocol for the transition from intravenous to subcutaneous insulin in patients with ACS when regular oral feeding was resumed.

Heart failure (HF) and chronic obstructive pulmonary disease (COPD) frequently co-exist, and each is a major public health issue. In a large cohort of hospitalized HF patients, we evaluated: (i) the impact of COPD on clinical outcomes; (ii) whether outcomes and treatments changed from 2002 to 2009; and (iii) the relationship between outcomes and treatments focusing on beta-blockers (BBs) and bronchodilators (BDs).From linkable Lombardy administrative health databases, we selected individuals with a discharge diagnosis of HF with or without concomitant COPD (HF yesCOPD and HF noCOPD) in 2002 and 2009. Patients were followed up for 4 years. Outcomes were total mortality, first readmission for HF, and their combination. Unadjusted and adjusted Cox proportional models and competing risk analyses were used. We identified 11 274 patients with HF noCOPD and 2837 with HF yesCOPD. HF yesCOPD patients in 2002 and 2009 had a 20% higher risk of the outcomes. From 2002 to 2009, BB and BD prescriptions increased significantly. In HF noCOPD patients, risks for mortality [adjusted hazard ratio (HR) 0.91, 95% confidence interval (CI) 0.86-0.97], first HF readmission (HR 0.79, 95% CI 0.74-0.85), and the combined endpoint (HR 0.88, 95% CI 0.84-0.92) declined (all P0.003) while in HF yesCOPD only the risk for first HF readmission dropped (HR 0.86, 95% CI 0.76-0.97; P = 0.018). BBs were associated with significantly lower mortality in both groups, but with a higher risk for first HF readmission in HF noCOPD. Outcomes did not significantly differ in HF yesCOPD treated or not with BDs.The prognosis of patients hospitalized for HF, either with or without COPD, seemed to improve between 2002 and 2009, with possibly better survival of those on BBs. Because of residual confounding in observational studies, a randomized controlled trial should be considered to confirm these results.

Although high cardiovascular risk patients should be the main target of preventive strategies, modifiable risk factors are often inadequately controlled.To assess feasibility and results of a comprehensive personalized method for cardiovascular prevention in high risk patients followed by their general practitioner.Between 2004 and 2007, 12,513 patients (mean age 64.0 ± 9.5 years; 61.5% males) with multiple cardiovascular risk factors or history of atherosclerotic disease were identified and followed for five years. If control of major modifiable cardiovascular risk factors (hypertension, hypercholesterolaemia, diabetes, obesity, smoking, unhealthy diet, physical inactivity) was sub-optimal, at baseline and yearly thereafter general practitioners planned with patients, with the help of a brief checklist, preventive interventions to improve the global risk profile. Main outcome was the control of the seven major modifiable cardiovascular risk factors during follow-up. Secondary outcome was the incidence of cardiovascular deaths and hospitalization for cardiovascular reasons according to the improvement in global cardiovascular risk profile during the first year.Control of all major modifiable risk factors except physical inactivity improved gradually and significantly (p 0.0001) during follow-up.The improvement in the global cardiovascular risk profile during the first year was independently and significantly associated with a lower rate of major cardiovascular events in the following years (hazard ratio 0.939; 95% confidence interval 0.887-0.994, p = 0.03).Our comprehensive, personalized method for cardiovascular risk prevention in people at high risk appears feasible in general practice. The improvement in the global cardiovascular risk profile was associated with a better prognosis.