Regional and temporal differences in the associations between cardiovascular disease and its classic risk factors: An analysis of 49 cohorts from 11 European countries.

AIMS: The regional and temporal differences in the associations between cardiovascular disease (CVD) and its classic risk factors are unknown. The current study examined these associations in different European regions over a 30-year period. METHODS: The study sample comprised 553818 individuals from 49 cohorts in 11 European countries (baseline: 1982-2012) who were followed up for a maximum of 10 years. Risk factors (sex, smoking, diabetes, non-HDL [high-density lipoprotein] cholesterol, systolic blood pressure [BP], and body mass index [BMI]) and CVD events (coronary heart disease or stroke) were harmonized across cohorts. Risk factor-outcome associations were analysed using multivariable-adjusted Cox regression models, and differences in associations were assessed using meta-regression. RESULTS: The differences in the risk factor-CVD associations between central Europe, northern Europe, southern Europe, and the United Kingdom were generally small. Men had a slightly higher hazard ratio (HR) in southern Europe (p = 0.043 for overall difference) and those with diabetes had a slightly lower HR in central Europe (p = 0.022 for overall difference) compared with the other regions. Of the six CVD risk factors, minor HR decreases per decade were observed for non-HDL cholesterol (7% per mmol/L; 95% confidence interval [CI], 3-10%) and systolic BP (4% per 20 mmHg; 95% CI, 1-8%), while a minor HR increase per decade was observed for BMI (7% per 10 kg/m2; 95% CI, 1-13%). CONCLUSION: The results demonstrate that all classic CVD risk factors are still relevant in Europe, irrespective of regional area. Preventive strategies should focus on risk factors with the greatest population attributable risk.

All classic CVD risk factors are still relevant in Europe, irrespective of regional area. The differences in the associations of CVD risk factors with overt CVD between regions of Europe are generally small. Minor temporal hazard decreases were observed for non-HDL cholesterol and systolic blood pressure, while a minor hazard increase was observed for body mass index.

Long-term follow-up of survivors of a first acute coronary syndrome: Results from the French MONICA registries from 2009 to 2017.

AIM: The objectives of the study were to characterize the long-term risk of first recurrence of acute coronary syndrome (ACS) among survivors of an incident ACS, as a function of the STEMI/NSTEMI/UA diagnosis. METHODS: Men and women (aged 35-74) hospitalized between 2009 and 2016 for an incident ACS in the French MONICA registries and still alive on discharge were followed-up until December 2017. Recurrent events were defined as the first (non-fatal or fatal) ACS occurring after hospital discharge from the incident event. RESULTS: The study comprised 15,739 incident ACSs with 63,777 patient-years of follow-up. The cumulative probability [95% confidence interval] of recurrent ACS was 6.7% [6.3-7.1%] at 1 year and 18.4% [17.4-19.5%] at 9 years. The cumulative probability of fatal recurrent ACS was 1.4% [1.2-1.5%] at 1 year and 4.3% [3.6-4.9%] at 9 years. The risk of recurrence did not depend on the type of the incident ACS after adjustment for confounding factors. The most frequent forms of recurrence were NSTEMI and UA. The presence of a major complication (OR = 1.59) and an impaired left ventricular ejection fraction (LVEF) (OR > 1.26) increased the risk of recurrence. The annual 1-year recurrence rates decreased from 7.4% in 2009 to 4.0% in 2016 (p < 0.001). CONCLUSION: The recurrence rate after an incident ACS remained high in France, and the risk of recurrence did not depend on the etiology of the first event. Our results emphasize the importance of targeting patients with a major complication and/or an impaired LVEF who are at a higher risk of recurrence.

Sex differences in time trends in acute coronary syndrome management and in 12-month lethality: Data from the French MONICA registries.

BACKGROUND: Sex differences in clinical presentation, patient care and fatal outcomes after an acute coronary syndrome (ACS) have been reported. However, recent improvements in the care and treatment of ACSs have not been assessed with regard to possible sex differences. AIM: To assess sex differences in trends between 2006 and 2016 in the characteristics of ACSs, their management, and the associated mortality. METHODS: We assessed all men and women (aged 35-74) covered by the MONICA registries in north, east and south-west France and having been hospitalized for an incident (first) ACS during a 12-month period in 2006 or a 6-month period in 2016. We analyzed the patients' clinical, biochemical, electrocardiographic and care-related data, and their vital status 28 days and 12 months after the ACS. RESULTS: In 2006, women were older (<0.0001) and had more atypical symptoms than men (p < 0.01). These differences were no longer statistically significant in 2016. Medical care improved in both men and women. However, revascularization treatment, prescriptions of platelet aggregation inhibitors, statins, and functional rehabilitation were still more frequently provided to men than to women (p < 0.01) in 2016, independently of confounders. The 28-day or 12-month case fatality was not different between men and women in both 2006 and 2016. CONCLUSIONS: The results of the present study evidenced an improvement over time in the management of ACS. However, although there were no longer sex differences in the patients' age and clinical presentation, women with ACS were still less likely than men to receive revascularization and pharmacological treatments in 2016.

Trends of in-hospital and out-of-hospital coronary heart disease mortality in French registries during the period 2000 to 2016.

PURPOSE: To estimate trends of in- and out-of-hospital Acute Coronary Events (ACE) mortality rates from 2000 to 2016 and their respective contributions to total ACE mortality in France. METHODS: All fatal coronary events occurring between January 2000 and December 2016 were recorded for patients age 35-74 in the French MONICA registries. Trends in age-standardized and crude mortality rates were expressed as annual percentage changes (APC). RESULTS: Between 2000 and 2016, 20,822 fatal events were recorded, of which 69.4% were out-of-hospital. Almost 90% of out-of-hospital deaths occurred at home. Decreases in ACE mortality were greater inside than outside the hospital (APC: -4.3% vs. -2.9% in men; -5.0% vs. -3.2% in women), resulting in a higher contribution of out-of-hospital mortality to overall ACE mortality, from 65.3% in 2000 to 71.4% in 2016. This trend was more pronounced for elderly than younger patients. CONCLUSIONS: Between 2000 and 2016, ACE mortality declined in France. This trend was more pronounced for in- than for out-of-hospital. These results underline the importance of out-of-hospital mortality in driving ACE mortality rates and the need to further investigate ways to reduce it.

Simple cardiovascular risk stratification by replacing total serum cholesterol with anthropometric measures: The MORGAM prospective cohort project.

To assess whether anthropometric measures (body mass index [BMI], waist-hip ratio [WHR], and estimated fat mass [EFM]) are independently associated with major adverse cardiovascular events (MACE), and to assess their added prognostic value compared with serum total-cholesterol. The study population comprised 109,509 individuals (53% men) from the MORGAM-Project, aged 19-97 years, without established cardiovascular disease, and not on antihypertensive treatment. While BMI was reported in all, WHR and EFM were reported in âˆ¼52,000 participants. Prognostic importance of anthropometric measurements and total-cholesterol was evaluated using adjusted Cox proportional-hazards regression, logistic regression, area under the receiver-operating-characteristic curve (AUCROC), and net reclassification improvement (NRI). The primary endpoint was MACE, a composite of stroke, myocardial infarction, or death from coronary heart disease. Age interacted significantly with anthropometric measures and total-cholesterol on MACE (P ≤ 0.003), and therefore age-stratified analyses (<50 versus ≥ 50 years) were performed. BMI, WHR, EFM, and total-cholesterol were independently associated with MACE (P ≤ 0.003) and resulted in significantly positive NRI when added to age, sex, smoking status, and systolic blood pressure. Only total-cholesterol increased discrimination ability (AUCROC difference; P < 0.001). In subjects < 50 years, the prediction model with total-cholesterol was superior to the model including BMI, but not superior to models containing WHR or EFM, while in those ≥ 50 years, the model with total-cholesterol was superior to all models containing anthropometric variables, whether assessed individually or combined. We found a potential role for replacing total-cholesterol with anthropometric measures for MACE-prediction among individuals < 50 years when laboratory measurements are unavailable, but not among those ≥ 50 years.

Comparison of clinical profiles and care for patients with incident versus recurrent acute coronary syndromes in France: Data from the MONICA registries.

BACKGROUND: Recurrence is common after an acute coronary syndrome (ACS). In order to better assess the prognosis for patients with ACS, we compared clinical profiles, treatments, and case fatality rates for incident vs. recurrent ACS. METHODS: We enrolled 1,459 men and women (age: 35-74) living in three geographical areas covered by French MONICA registries and who had been admitted to hospital for an ACS in 2015/2016. We recorded and compared the clinical characteristics and medical care for patients with an incident vs. a recurrent ACS. RESULTS: Overall, 431 (30%) had a recurrent ACS. Relative to patients with an incident ACS, patients with recurrence were older (p<0.0001), had a greater frequency of NSTEMI or UA (p<0.0001), were less likely to show typical symptoms (p = 0.045), were more likely to have an altered LVEF (p<0.0001) and co-morbidities. Angioplasty was less frequently performed among patients with recurrent than incident NSTEMI (p<0.05). There were no intergroup differences in the prescription of the recommended secondary prevention measures upon hospital discharge, except for functional rehabilitation more frequently prescribed among incident patients (p<0.0001). Although the crude 1-year mortality rate was higher for recurrent cases (14%) than for incident cases (8%) (p<0.05), this difference was no longer significant after adjustment for age, sex, region, diagnosis category and LVEF. CONCLUSION: Compared with incident patients, recurrent cases were more likely to have co-morbidities and to have suboptimal treatments prior to hospital stay, reinforcing the need for secondary prevention.

Alcohol intake and total mortality in 142 960 individuals from the MORGAM Project: a population-based study.

AIM: To test the association of alcohol consumption with total and cause-specific mortality risk. DESIGN: Prospective observational multi-centre population-based study. SETTING: Sixteen cohorts (15 from Europe) in the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) Project. PARTICIPANTS: A total of 142 960 individuals (mean age 50 ± 13 years, 53.9% men). MEASUREMENTS: Average alcohol intake by food frequency questionnaire, total and cause-specific mortality. FINDINGS: In comparison with life-time abstainers, consumption of alcohol less than 10 g/day was associated with an average 11% [95% confidence interval (CI) = 7-14%] reduction in the risk of total mortality, while intake > 20 g/day was associated with a 13% (95% CI = 7-20%) increase in the risk of total mortality. Comparable findings were observed for cardiovascular (CV) deaths. With regard to cancer, drinking up to 10 g/day was not associated with either mortality risk reduction or increase, while alcohol intake > 20 g/day was associated with a 22% (95% CI = 10-35%) increased risk of mortality. The association of alcohol with fatal outcomes was similar in men and women, differed somewhat between countries and was more apparent in individuals preferring wine, suggesting that benefits may not be due to ethanol but other ingredients. Mediation analysis showed that high-density lipoprotein cholesterol explained 2.9 and 18.7% of the association between low alcohol intake and total as well as CV mortality, respectively. CONCLUSIONS: In comparison with life-time abstainers, consuming less than one drink per day (nadir at 5 g/day) was associated with a reduced risk of total, cardiovascular and other causes mortality, except cancer. Intake of more than two drinks per day was associated with an increased risk of total, cardiovascular and especially cancer mortality.

Predictive Importance of Blood Pressure Characteristics With Increasing Age in Healthy Men and Women: The MORGAM Project.

[Figure: see text].

Comparison of Short- and Long-Term Prognosis between ST-Elevation and Non-ST-Elevation Myocardial Infarction.

BACKGROUND: Available data comparing long-term prognosis according to the type of acute coronary syndrome (ACS) are scarce, contradictory, and outdated. Our aim was to compare short- and long-term mortality in ST-elevated (STEMI) and non-ST-elevated myocardial infarction (non-STEMI) ACS patients. METHODS: Patients presenting with an inaugural ACS during the year 2006 and living in one of the three areas in France covered by the Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) registry were included. RESULTS: A total of 1822 patients with a first ACS-1121 (61.5%) STEMI and 701 (38.5%) non-STEMI-were included in the study. At the 28-day follow-up, the mortality rates were 6.7% and 4.7% (p = 0.09) for STEMI and non-STEMI patients, respectively, and after adjustment of potential confounding factors, the 28-day probability of death was significantly lower for non-STEMI ACS patients (Odds Ratio = 0.58 (0.36-0.94), p = 0.03). At the 10-year follow-up, the death rates were 19.6% and 22.8% (p = 0.11) for STEMI and non-STEMI patients, respectively, and after adjustment of potential confounding factors, the 10-year probability of death did not significantly differ between non-STEMI and STEMI events (OR = 1.07 (0.83-1.38), p = 0.59). Over the first year, the mortality rate was 7.2%; it then decreased and stabilized at 1.7% per year between the 2nd and 10th year following ACS. CONCLUSION: STEMI patients have a worse vital prognosis than non-STEMI patients within 28 days following ACS. However, at the 10-year follow-up, STEMI and non-STEMI patients have a similar vital prognosis. From the 2nd year onwards following the occurrence of a first ACS, the patients become stable coronary artery disease patients with an annual mortality rate in the 2% range, regardless of the type of ACS they initially present with.

Association between overall fruit and vegetable intake, and fruit and vegetable sub-types and blood pressure: the PRIME study (Prospective Epidemiological Study of Myocardial Infarction).

Increased fruit and vegetable (FV) intake is associated with reduced blood pressure (BP). However, it is not clear whether the effect of FV on BP depends on the type of FV consumed. Furthermore, there is limited research regarding the comparative effect of juices or whole FV on BP. Baseline data from a prospective cohort study of 10 660 men aged 50-59 years examined not only the cross-sectional association between total FV intake but also specific types of FV and BP in France and Northern Ireland. BP was measured, and dietary intake assessed using FFQ. After adjusting for confounders, both systolic BP (SBP) and diastolic BP (DBP) were significantly inversely associated with total fruit, vegetable and fruit juice intake; however, when examined according to fruit or vegetable sub-type (citrus fruit, other fruit, fruit juices, cooked vegetables and raw vegetables), only the other fruit and raw vegetable categories were consistently associated with reduced SBP and DBP. In relation to the risk of hypertension based on SBP >140 mmHg, the OR for total fruit, vegetable and fruit juice intake (per fourth) was 0·95 (95 % CI 0·91, 1·00), with the same estimates being 0·98 (95 % CI 0·94, 1·02) for citrus fruit (per fourth), 1·02 (95 % CI 0·98, 1·06) for fruit juice (per fourth), 0·93 (95 % CI 0·89, 0·98) for other fruit (per fourth), 1·05 (95 % CI 0·99, 1·10) for cooked vegetable (per fourth) and 0·86 (95 % CI 0·80, 0·91) for raw vegetable intakes (per fourth). Similar results were obtained for DBP. In conclusion, a high overall intake of fruit, vegetables and fruit juice was inversely associated with SBP, DBP and risk of hypertension, but this differed by FV sub-type, suggesting that the strength of the association between FV sub-types and BP might be related to the type consumed, or to processing or cooking-related factors.

Association of low plasma antioxidant levels with all-cause mortality and coronary events in healthy middle-aged men from France and Northern Ireland in the PRIME study.

BACKGROUND: The main underlying risk factors associated with coronary heart disease (CHD) are modifiable and oxidative injury and systemic inflammatory damage represent key aetiological factors associated with the development and progression of CHD and premature mortality. OBJECTIVE: To examine associations of plasma antioxidant status with all-cause mortality and fatal or non-fatal cardiovascular events. DESIGN: The PRIME study prospectively evaluated 9709 men aged 50-59 years between 1991 and 1993 in Northern Ireland and France who were free of CHD at recruitment and followed annually for deaths and cardiovascular events for 10 years. Serum concentrations of vitamin C, retinol, two forms of vitamin E (α- and γ-tocopherol) and six carotenoids were quantified by high-performance liquid chromatography. Baseline conventional risk factors were considered, as well as socioeconomic differences and lifestyle behaviours including diet, smoking habit, physical activity, and alcohol consumption through Cox regression analyses. RESULTS: At 10 years, there were 538 deaths from any cause and 440 fatal or non-fatal cardiovascular events. After adjustment for country, age, systolic blood pressure, diabetes, body mass index, cholesterol, high density lipoprotein cholesterol, triglycerides, height, total physical activity, alcohol consumption and smoking habit, higher levels of all antioxidants were associated with significantly lower risk of all-cause mortality, with the exception of γ-tocopherol. Only retinol was significantly associated with decreased risk of cardiovascular events in a fully adjusted model. CONCLUSIONS: Low antioxidant levels contribute to the gradient of all-cause mortality and cardiovascular incidence independent of lifestyle behaviours and traditional cardiovascular and socioeconomic risk factors.

Short-Term Effects of Air Pollution on Coronary Events in Strasbourg, France-Importance of Seasonal Variations.

The aim of this study, is to investigate the effects of a short-term exposure to air pollutants, as assessed by Nitrogen dioxide (NO2), Particulate Matter PM2,5 and PM10 concentrations, on coronary event onsets in Strasbourg, France. An observational, analytical, retrospective, epidemiological study was conducted in Strasbourg between 1 January 2012 and 31 December 2014. Higher daily coronary events rates were evidenced when NO2 concentrations were measured above 40 µg/m3 (1.258 (95% CI 1.142-1.374) vs. 1.110 (95% CI 1.033-1.186); p = 0.015). The NO2 concentration was higher than 30 µg/m3 for 677 days (61.8%). Higher daily coronary events rates were evidenced when NO2 concentrations were measured above 30 µg/m3 (1.208 (95% CI 1.128-1.289) vs. 1.067 (95% CI 0.961-1.172) p = 0.009). A marked seasonality of NO2, PM2.5, and PM10 concentrations characterized by an increase during winter and a decrease during the summer could be established. The seasonality of coronary events was evidenced simultaneously. After adjustments were made to account for the time and the month, no independent impact of NO2, PM2.5 or PM10 on daily coronary events could be demonstrated.

Combined Influence of Waist and Hip Circumference on Risk of Death in a Large Cohort of European and Australian Adults.

Background Waist circumference and hip circumference are both strongly associated with risk of death; however, their joint association has rarely been investigated. Methods and Results The MONICA Risk, Genetics, Archiving, and Monograph (MORGAM) Project was conducted in 30 cohorts from 11 countries; 90 487 men and women, aged 30 to 74 years, predominantly white, with no history of cardiovascular disease, were recruited in 1986 to 2010 and followed up for up to 24 years. Hazard ratios were estimated using sex-specific Cox models, stratified by cohort, with age as the time scale. Models included baseline categorical obesity measures, age, total and high-density lipoprotein cholesterol, systolic blood pressure, antihypertensive drugs, smoking, and diabetes mellitus. A total of 9105 all-cause deaths were recorded during a median follow-up of 10 years. Hazard ratios for all-cause death presented J- or U-shaped associations with most obesity measures. With waist and hip circumference included in the same model, for all hip sizes, having a smaller waist was strongly associated with lower risk of death, except for men with the smallest hips. In addition, among those with smaller waists, hip size was strongly negatively associated with risk of death, with ≈20% more people identified as being at increased risk compared with waist circumference alone. Conclusions A more complex relationship between hip circumference, waist circumference, and risk of death is revealed when both measures are considered simultaneously. This is particularly true for individuals with smaller waists, where having larger hips was protective. Considering both waist and hip circumference in the clinical setting could help to best identify those at increased risk of death.

Does Estimated Pulse Wave Velocity Add Prognostic Information?: MORGAM Prospective Cohort Project.

The Reference Values for Arterial Stiffness Collaboration has derived an equation using age and mean blood pressure to estimated pulse wave velocity (ePWV), which predicted cardiovascular events independently of Systematic COoronary Risk Evaluation (SCORE) and Framingham Risk Score. The study aim was to investigate the independent association between ePWV and clinical outcomes in 107 599 apparently healthy subjects (53% men) aged 19 to 97 years from the MORGAM Project who were included between 1982 and 2002 in 38 cohorts from 11 countries. Using multiple Cox-regression analyses, the predictive value of ePWV was calculated adjusting for country of inclusion and either SCORE, Framingham Risk Score, or traditional cardiovascular risk factors (age, sex, smoking, systolic blood pressure, body mass index [BMI], total and high-density lipoprotein cholesterol). Cardiovascular mortality consisted of fatal stroke, fatal myocardial infarction, or coronary death, and the composite cardiovascular end point consisted of stroke, myocardial infarction, or coronary death. Model discrimination was assessed using Harrell's C-statistic. Adjusting for country and logSCORE or Framingham Risk Score, ePWV was associated with all-cause mortality (hazard ratio, 1.23 [95% CI 1.20-1.25] per m/s or 1.32 [1.29-1.34]), cardiovascular mortality (1.26 [1.21-1.32] or 1.35 [1.31-1.40]), and composite cardiovascular end point (1.19 [1.16-1.22] or 1.23 [1.20-1.25]; all P<0.001). However, after adjusting for traditional cardiovascular risk factors, ePWV was only associated with all-cause mortality (1.15 [1.08-1.22], P<0.001) and not with cardiovascular mortality (0.97 [0.91-1.03]) nor composite cardiovascular end point (1.10 [0.97-1.26]). The areas under the last 3 receiver operator characteristic curves remained unchanged when adding ePWV. Elevated ePWV was associated with subsequent mortality and cardiovascular morbidity independently of systematic coronary risk evaluation and Framingham Risk Score but not independently of traditional cardiovascular risk factors.

Coronary heart disease incidence still decreased between 2006 and 2014 in France, except in young age groups: Results from the French MONICA registries.

BACKGROUND: Over the past few decades decreases in coronary heart disease morbidity and mortality rates have been observed throughout the western world. We sought to determine whether the acute coronary event rates had decreased between 2006 and 2014 among French adults, and whether there were sex and age-specific differences. METHODS: We examined the French MONICA population-based registries monitoring the Lille urban area in northern France, the Bas-Rhin county in north-eastern France and the Haute Garonne county in south-western France. All acute coronary events among men and women aged 35-74 were collected. RESULTS: Over the study period, the age-standardised attack rates decreased in both men (annual percentage change -1.5%, P = 0.0006) and women (annual percentage change -2.1%, P = 0.002). Also, the age-standardised incidence rates decreased in both men (annual percentage change -0.9%, P = 0.03) and women (annual percentage change -1.8%, P = 0.002) due to decreases in the 65-74 year age group. In men, age-standardised mortality rates decreased by 3.5% per year (P = 0.0004), especially in the 55-64 and 65-74 year age groups. In women, these rates decreased by 4.3% per year (P = 0.0009), particularly in the 35-44 and 65-74 year age groups. We also observed significant decreases in case fatality among both men (annual percentage change -1.7%, P < 0.0001) and women (annual percentage change -1.9%, P = 0.009). CONCLUSIONS: Downward trends in acute coronary event attack, incidence and mortality rates were observed between 2006 and 2014 in men and women. This effect was age dependent and was primarily due to decreases in the 65-74 year age group. There were no substantial declines in the younger age groups except for mortality in young women. Prevention measures still need to be strengthened, particularly in young adults.

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.

Prevalence and Treatment of Familial Hypercholesterolemia in France.

BACKGROUND: Familial hypercholesterolemia (FH) is known to be underdiagnosed and undertreated. The prevalence of heterozygous FH is estimated to be 1 in 500. Nevertheless, a recent meta-analysis of screening in the general population seems to show that the prevalence of FH is more likely to be 1 in 250. METHODS: Analysis was based on the third French MONICA and MONALISA population surveys. Participants were randomly recruited in 1995 and 2005 from the general population of 3 regions of France. FH was diagnosed using a modified version of the Dutch Lipid Clinic Network (DLCN) without genetic testing. RESULTS: The DLCN score was assessed in 7928 participants aged 35 to 74 years; 50% were men. The prevalence of definite or probable FH was 0.85% (95% CI, 0.63-1.06). Among patients with definite or probable FH, 12% had histories of premature cardiovascular disease (vs less than 1% among subjects without FH; P < 0.0001), 70% were treated (13% with high-intensity, 83% with moderate-intensity, and 4% with low-intensity statin therapy), 90% had cholesterol screening within the past 12 months, and 97% were aware of their hypercholesterolemia. None reached the recommended low-density lipoprotein cholesterol (LDL-C) target (< 2.5 or < 1.8 mmol/L for subjects in primary prevention vs in secondary prevention or with diabetes, respectively), with a mean distance to target of 3.0 mmol/L. CONCLUSIONS: In a sample from the French general population aged 35 to 74 years, the prevalence of FH was close to 1 in 120, and the patients with FH were undertreated.

Effectiveness and efficiency of tele-expertise for improving access to retinopathy screening among 351 neonates in a secondary care center: An observational, controlled before-after study.

In France, secondary care hospitals encounter difficulties to adhere to retinopathy of prematurity (ROP) screening guidelines. Our objective was to assess the effectiveness and efficacy of a tele-expertise program for ROP screening in neonatal intensive care units without on-site ophthalmologists. We evaluated the impact of a tele-expertise program funded by the Paris Region Health Authority in a secondary care center general hospital of the Paris Region (CHSF), where there was previously no on-site ophthalmologist. We performed an observational, controlled before-after study, with a university tertiary care center with on-site ophthalmologists (Port-Royal) as the control group. Recruitment and data collection for both periods took place from 1 January 2012 to 31 December 31 2012, and from 1 January 2014 to 31 March 2015. The primary endpoint was the percentage of compliance with screening guidelines, secondary endpoints included pain scores and costs. Over the two periods, at total of 351 infants were recruited in the CHSF. Implementation of the tele-expertise resulted in an absolute +57.3% increase in the proportion of examinations realized in accordance with guidelines (3.8% during the "before" period and 61.1% during the "after" period, p<0.001). As compared with the control group, the proportion of infants appropriately screened improved (57.5% versus 43.1%, p = 0.002); median pain score on the acute pain rating scale for neonates during examination was significantly higher (median score 5.5/10, range [2.5-5.7] versus 2.0/10, range [1.0-3.1], p = 0.002). Screening rates in the control group remained unchanged. The average cost per examination increased from €337 in the "before" period to €353 in the "after period" in the tele-expertise group. The implementation of tele-expertise for ROP screening in the CHSF medical center resulted in a major improvement of access to care with a small cost increase. The issue of pain control during examination with tele-expertise should be further addressed.

Methodological issues of assessing the risk of a second cancer occurring in the same site as a first cancer using registry data.

OBJECTIVE: To present methodological issues that can arise with the assessment of the risk of a second primary cancer (SPC) occurring in the same site as a first cancer using registry data. MATERIAL AND METHODS: Data from ten French cancer registries were used, including data for patients with a first prostate cancer (in males), breast cancer (in females), and colon, lung and kidney cancer (in both sexes) diagnosed between 1989 and 2004. Standardized incidence ratios (SIRs) of SPC were computed by excluding, or not, the risk of an SPC at the same site. RESULTS: For prostate cancer, the SIR dropped from 1.11 to 0.72 when the risk of SPC of the prostate was included. SIRs increased from 1.36 to 1.45, from 1.14 to 1.21, from 1.57 to 2.01, and from 1.37 to 1.51 for breast, colon, lung, and kidney respectively. CONCLUSION: The inclusion, or not, of an SPC at the same site can impact on SPC risk estimates.

Score of Adherence to 2016 European Cardiovascular Prevention Guidelines Predicts Cardiovascular and All-Cause Mortality in the General Population.

BACKGROUND: Guidelines on cardiovascular (CV) disease prevention promote healthy lifestyle behaviours and CV risk factor control to reduce CV risk. The effect of adherence to these guidelines on CV and all-cause mortality is not well known. METHODS: We assessed the effect of baseline adherence to "2016 European Guidelines on CV Disease Prevention in Clinical Practice" on long-term CV and all-cause mortality in a sample recruited from the French general population. Analysis was on the basis of the Third French Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) population-based survey (recruitment period: 1994-1997). We built an adherence score to European guidelines, considering adherence to recommendations for smoking, drinking, physical activity, body mass index, blood pressure, low-density and high-density lipoprotein cholesterol, fasting blood glucose, and diet at baseline. Vital status was obtained 18 years after inclusion. Statistical analysis was on the basis of multivariate Cox modelling. RESULTS: Adherence score was assessed in 1311 apparently healthy participants aged 35-64 years (73% men). During the follow-up, 186 deaths occurred (41 were due to a CV cause). Considering CV mortality, the adjusted hazard ratio for subjects in the fourth quartile of the adherence score (worse adherence) was 3.12 (95% confidence interval [CI], 1.62-6.01; P = 0.001), compared with subjects in the first, second, or third quartile (best adherence). Considering all-cause mortality, the adjusted hazard ratio for subjects in the fourth quartile of the adherence score was 2.27 (95% CI, 1.68-3.06; P < 0.001). CONCLUSIONS: Better baseline adherence to European guidelines on CV disease prevention was associated with a significantly reduced long-term CV and all-cause mortality in a sample from the French general population.