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Summary Background The P2Y 13 purinergic receptor regulates hepatic high-density lipoprotein uptake and biliary sterol secretion; it acts downstream of the membrane ecto-F1-adenosine triphosphatase, which generates extracellular adenosine diphosphate that selectively activates P2Y 13 , resulting in high-density lipoprotein endocytosis. Previous studies have shown that the serum concentration of the F1-adenosine triphosphatase inhibitor inhibitory factor 1 is negatively associated with cardiovascular risk. Aim To evaluate whether p2y 13 genetic variants affect cardiovascular risk. Methods Direct sequencing of the p2y 13 coding and flanking regions was performed in a subcohort of 168 men aged 45–74 years with stable coronary artery disease and 173 control subjects from the GENES study. The two most frequent mutations, rs3732757 and rs1466684, were genotyped in 767 patients with coronary artery disease and 789 control subjects, and their association with cardiovascular risk markers was analysed. Results Carriers of the rs3732757 261 T and rs1466684 557G alleles represented 9% and 27.5% of the entire population, respectively. The allele frequencies were identical in patients with coronary artery disease and control subjects. The presence of 261 T was associated with higher concentrations of plasma lipoprotein A-I and inhibitory factor 1, increased fat mass and a lower heart rate. Moreover, the proportion of patients with coronary artery disease with a pejorative systolic ankle − brachial index was lower in carriers of the 261 T allele. In both populations, the 557G allele was associated with increased concentrations of lipoprotein(a), and an allele dose effect was observed. Conclusions Two frequent p2y13 variants are associated with specific bioclinical markers of cardiovascular risk. Although neither one of these variants appears to be related to the development of atherosclerotic disease, they may modulate the risk of additional cardiovascular complications.

BACKGROUND A small proportion of familial hypercholesterolemia (FH) patients can adequately control this condition, although achieving the recommended targets for low-density lipoprotein cholesterol (LDL-c) levels remains a challenge. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are new and potent lipid-lowering drugs. However, there is scarce literature on real-world data about their use in patients with FH. MATERIAL AND METHODS We examined the reduction in LDL-c levels from the baseline, after PCSK9i initiation in heterozygous familial hypercholesterolemia patients referred for lipoprotein apheresis in our regional lipid clinic. The study was conducted from March 2018 to September 2019, the period immediately after PCSK9i reimbursement was available in France. PCSK9i was added on top of the patients' maximal tolerated lipid-lowering regimens. RESULTS The study had 123 patients with heterozygous FH. The mean age of the patients was 59±11 years. The mean baseline LDL-c for all the participants was 277±78 mg/dl. It was 283±81 mg/dl in the PCSK9i monotherapy group (n=83), 247±68 mg/dl in the PCSK9i plus ezetimibe group (n=12), and 264±78 mg/dl in the PCSK9i plus statin and ezetimibe group (n=28). The mean decrease observed in the LDL-c level from baseline was 136±70 mg/dl (n=123), 125±60 mg/dl (n=83), 103±77 mg/dl (n=12), and 175±70 mg/dl (n=28), respectively. CONCLUSIONS An overall reduction of 49.1% from the baseline LDL-c was observed in the heterozygous FH population after PCSK9i initiation in a real-world experience. The group treated with PCSK9i ezetimibe plus statin showed further reduction of their LDL-c levels with a better responder rate, achieving the target 50% reduction in LDL-c from the baseline.

Background Understanding determinants of coronary calcium score could lead to the development of new preventive actions for reducing cardiovascular risk. Our hypothesis is that major cardiovascular risk factors are linked with coronary calcium score, but the parameters associated with moderate or high scores could be different. Purpose The aim of our study was to explore the potential determinants of moderate and high elevation of coronary calcium score in a population of patients at intermediate cardiovascular risk. Methods We conducted a cross-sectional analysis, using data from a prospective cohort. Our study population was composed of people presenting with cardiovascular risk factors, who were referred by their attending physician for a complete assessment of their risk factors and for screening for silent cardiovascular disease. People in secondary prevention could also be referred. Coronary calcium score was assessed by cardiac CT scan. We used the following categories for classifying patients according to their coronary calcium score: low (0–100 AU (Agatston units)); moderate (101–300 AU) and high calcium score (greater than 300 AU). We performed a descriptive analysis and then we built a multinomial logistic regression model, using the low calcium score category as reference. Results Among the 1585 patients included in the database, we analyzed data from 1402 individuals who beneficiated from coronary calcium scoring. The sample included 714 (51%) men, and 144 (10%) people with a history of cardiovascular disease. Mean age was 59 yrs. Data from the multivariate analysis showed that age (OR=1.07; 95% CI [1.054–1.091] for 1-year increase), gender (OR=0.461; 95% CI [0.330–0.643] for women versus men) and smoking more than 20 cigarettes per day (OR=2.893; 95% CI [1.207–6.935]) were associated with a moderate calcium score. Variables associated with a high calcium score were: age (OR=1.097; 95% CI [1.076–1.119] for 1-year increase), gender (OR=0.221; 95% CI [0.151–0.323] for women vs men), treated dyslipidemia (OR=2.108; 95% CI [1.467–3.027]), treated hypertension (OR=2.199; 95% CI [1.523–3.175]), and history of cardiovascular disease (OR=4.138; 95% CI [2.510–6.823]). Conclusions In this study, well-known and modifiable cardiovascular risk factors are associated with calcium score. However, our results highlight that determinants of moderate and high scores may be different. While tobacco is associated with a higher risk of moderate calcium score, hypertension and dyslipidemia appear to be preferentially linked with the highest scores. It is thus appropriate that the 2019 ESC/EAS guidelines for dyslipidemias have classified patients with hypertension and dyslipidemia in the high risk category. Funding Acknowledgement Type of funding source: None

Case series Patients: Male, 44-year-old • Female, 71-year-old Final Diagnosis: Resistance to PCSK9I overcomed by adding statin Symptoms: Dyslipidemia Medication: — Clinical Procedure: — Specialty: Cardiology Objective: Unusual or unexpected effect of treatment Background: Real-life data on the efficacy of monotherapy with PCSK9 inhibitors are scarce. Most cohort studies have examined populations that are not severely dyslipidemic and are receiving combined therapy rather than monotherapy. Case Reports: From a series of 167 alirocumab prescriptions, we present a case of complete nonresponse and one of low response to monotherapy with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in 2 patients with heterozygous familial hypercholesterolemia and abnormalities of the low-density lipoprotein cholesterol (LDL-C) receptor. In these cases, PCSK9 inhibitors were ineffective when used alone to reduce the LDL-C level, but the addition of statin led to a dramatic improvement. Conclusions: As PCSK9 inhibitors become more commonly prescribed, more cases of nonresponse to PCSK9 inhibitors will be identified. Prospective studies are needed to investigate the efficacy of treatment with the monoclonal antibodies PCSK9 inhibitors in the context of LDL-C receptor abnormalities and to determine whether a genetic explanation exists for interindividual differences in response.

Stable coronary heart disease (CHD) patients are advised to practice regular physical activity (PA). However, data on very long-term prognosis impact of regular exercise remain scarce. We aimed to evaluate the impact of physical activity level on mortality at long term in stable CHD patients. We analyzed 822 patients with stable CHD. They answered questionnaires on medical history, underwent a standardized clinical examination, and provided a fasting blood sample. PA was evaluated by the MOSPA questionnaire. Three tertiles of patients were individualized according to PA level: 0.0-9 Metabolic Equivalent of Task (METs) hour per week (n = 267); 10-39.9 METs hour per week (n = 279); and ≥40 METs hour per week (n = 276). After a median follow-up of 14.6 years, 324 patients had died. In a multivariate analysis adjusted for age, dyslipidemia, smoking status, diabetes, high blood pressure, waist circumference, left ventricular ejection fraction, Gensini score, heart rate, ankle-brachial index and duration of disease, physical activity was significantly and independently associated with all-cause mortality. Compared to the lowest PA tertile, both the median and the highest PA tertiles, were associated to a reduction of all-cause mortality risk with hazard ratios at 0.79 (95%confidence interval [0.61:1.03], P = 0.08) and 0.71 ([0.53:0.96], P = 0.025) respectively; P for trend = 0.02. Adjusted hazard ratios for an increase of 10 METs hour per week was 0.95 [0.92 to 0.98], (P0.002). In conclusion, our study demonstrates an independent association between PA and long term vital prognosis with a 5% total mortality decrease for an increase of 10 METs hour per week.

Summary Background Cardiovascular disease (CVD) is the primary cause of premature death in Western countries. Aim To assess the effect of patient ignorance of CVD risk modifiers on mortality. Methods We studied 4930 men and women in primary prevention, who consulted at the Department of Preventive Cardiology of a university hospital in France from 1995 to 2011. Questionnaires on socioeconomic level, medical history, cardiovascular risk factors, knowledge of CVD, drug intake, lifestyle and dietary recommendations, and adherence to treatments were administered by trained medical staff. Vital status (cause and date of death, in patients who died) was obtained through the French National Database. Multivariable predictive relationships with total mortality were evaluated using the Cox proportional hazards model. Results Mean follow-up was 8.6 years; 123 deaths, including 31 cardiovascular deaths, were recorded. Overall, 1305 patients (26%) were ignorant of CVD preventive measures; their mean age (53 years) was similar to that of the non-ignorant population, but most were men with a low educational level, a higher body mass index and significantly more cardiovascular risk factors (diabetes, hypertension). The ignorant group's lifestyle did not conform to cardiovascular guidelines, with less physical activity and more frequent inappropriate diet and smoking. All-cause and cardiovascular mortalities were higher among these patients. In the multivariable analysis, after adjusting for age, sex, smoking status, diabetes, hypertension, body mass index and educational status, ignorance of CVD preventive measures remained significantly associated with all-cause mortality (hazard ratio 1.93, 95% confidence interval 1.31–2.83; P Conclusion Ignorance of cardiovascular risk modifiers was significantly associated with all-cause mortality in a general French population.

The P2YTo evaluate whether p2yDirect sequencing of the p2yCarriers of the rs3732757 261T and rs1466684 557G alleles represented 9% and 27.5% of the entire population, respectively. The allele frequencies were identical in patients with coronary artery disease and control subjects. The presence of 261T was associated with higher concentrations of plasma lipoprotein A-I and inhibitory factor 1, increased fat mass and a lower heart rate. Moreover, the proportion of patients with coronary artery disease with a pejorative systolic ankle-brachial index was lower in carriers of the 261T allele. In both populations, the 557G allele was associated with increased concentrations of lipoprotein(a), and an allele dose effect was observed.Two frequent p2y13 variants are associated with specific bioclinical markers of cardiovascular risk. Although neither one of these variants appears to be related to the development of atherosclerotic disease, they may modulate the risk of additional cardiovascular complications.

BACKGROUND: Familial hypercholesterolemia (FH) is a common autosomal dominant disease associated with premature coronary heart disease (CHD). Studies tend to show that patients with FH associated with an identified mutation (mutation+ FH) are at higher risk than patients without an identified mutation (mutation– FH). We compared the clinical and biological profile and the risk of CHD in patients with mutation+ FH and mutation– FH. HYPOTHESIS: In addition to LDL‐C, a pathogenic mutation predicts premature CHD in FH. METHODS: We successively included all patients with suspected FH (LDL‐C > 190 mg/dL if age > 18 years; LDL‐C > 160 mg/dL if age

SummaryBackgroundHeterozygous familial hypercholesterolaemia (HeFH) is a severe autosomal dominant disease that is underdiagnosed, inadequately treated and has a severe long-term cardiovascular risk. Few studies have evaluated the long-term risk of high low-density lipoprotein cholesterol (LDL-C) concentrations.AimTo evaluate long-term mortality in a large cohort of healthy subjects, according to LDL-C concentrations.MethodsBased on a sample of 6956 subjects visiting a preventive cardiology department, we selected adult subjects without a personal history of cardiovascular disease. From 1995 to 2011, 4930 healthy subjects were examined and followed up until 31 December 2011. All-cause deaths were collected exhaustively. A Cox-based multivariable analysis evaluated long-term total mortality risk according to Dutch Lipid Clinic Network (DLCN) LDL-C concentrations.ResultsAfter a mean follow-up of 8.6 years, 123 all-cause deaths were recorded (cumulative mortality rate, 2.5%). In the final multivariable model, major risk factors such as age, sex, tobacco use and diabetes were significantly associated with mortality. After adjustment for age, sex, tobacco use, hypertension, diabetes and statin therapy, and in comparison with subjects with LDL-C

Background and aims A high level of serum alkaline phosphatase (ALP) is associated with an increased risk of mortality and myocardial infarction. ALP hydrolyses inorganic pyrophosphate, which is a strong inhibitor of calcium phosphate deposition. The aim of this study was to determine whether ALP is associated with the coronary artery calcium score (CACS). Methods We examined the association of CACS, assessed by computed tomography scanning, and ALP, in 500 patients consecutively recruited, free of cardiovascular disease. The CACS were categorized into two groups: no calcification (CACS = 0) (n = 187) and with calcification (CACS>0) (n = 313). ALP activity was divided into three tertile groups: low ALP level ( 66 IU/L). Results The mean age was 60.9 ± 10.8 years, 49.6% of the patients were women. ALP ranged from 22 to 164 IU/L (mean 62.6 IU/L, SD 19.3). In univariate analysis, traditional cardiovascular risk factors, statin use (p = 0.001), and ALP (p = 0.001) were significantly associated with CACS. After adjusting for cardiovascular risk factors, only age (p = 0.001) and sex (p = 0.001) were independently associated with CACS. Compared to the tertile group with low levels of ALP, the intermediate tertile group [OR 2.11, 95% CI (1.12; 3.96), p = 0.02], as well as the high tertile group [OR 3.89, 95% CI (2.01; 7.54), p = 0.001)], was independently associated with CACS. Conclusions In patients free of cardiovascular disease, high ALP levels are positively and independently associated with coronary artery calcification. The metabolic pathway of ALP and inorganic pyrophosphate could be a target for new therapies against vascular calcification.

Background All-cause mortality is reduced by 20–30% in healthy individuals and in coronary heart disease (CHD) patients. Purpose The objective of this study was to analyze the long-term impact of physical activity (PA) on all-cause mortality in stable CHD patients. Methods From May 2001 to March 2004, we included 834 consecutive male CHD patients (aged 45–74 years) in the Genetique et ENvironnement en Europe du Sud (GENES) study. Detailed baseline assessment of net energy expenditure in relation with work, commuting and leisure time PA in the preceding year, according to category of activity, was obtained by the MOSPA questionnaire. PA was expressed in weekly metabolic equivalent scores (MET) hours per week. Results Final analysis was performed in 822 patients with complete data (60.1 ± 8.1 years). Over an average of 12.5 (± 4.3) years of follow-up (median 14.6), 324 patients died (39.4%). The distribution of mortality rates according to the MET tertiles (10, 40) was (from the lowest to the highest tertile) 46.1%, 23.4% and 17.6%, respectively (P Conclusion Our study shows an independent association of PA with mortality with a 5% total mortality decrease for an increase of 10 MET per week. Stable CHD should undergo vigorous aerobic PA in order to improve prognosis.

Introduction: High-density lipoprotein cholesterol (HDL-C) may not be the best clinical measure of HDL for assessing cardiovascular risk. Serum inhibitor factor 1 (IF1), an endogenous inhibitor of the ecto-F1-ATPase apoA-I receptor, has been identified as an independent determinant of HDL-C associated with low risk of coronary artery disease (CAD). Objective: To determine the relationship between serum IF1 concentration and mortality in stable CAD patients in comparison with HDL-C and apoA-I Methods: Serum IF1 was measured in 577 coronary male patients (enrollment age 45-74 years; enrollment period, 2001-2004) from the GENES (Genetique et ENvironement en Europe du Sud) study. Vital status was assessed yearly through December 31, 2013. Results: During a median follow up of 11 years, mortality rate was 29.5%. Cardiovascular mortality accounted for the majority (62.5%) of deaths. Serum IF1 (median value: 0.42 mg/mL) was positively correlated with HDL-C and apoA-I, and negatively with triglycerides and the severity of CAD (Gensini, Duke-Jeopardy scores). Mortality was lower the higher the quartile score for IF1 and apoA-I, but not for HDL-C. Inverse associations of IF1 and apoA-I with mortality remained significant, even after multivariate adjustments for classical cardiovascular risk factors - age, smoking, diabetes, dyslipidemia, waist circumference, physical activity and CRP. Furthermore, associations of the highest IF1 quartile with mortality reduction remained significant after further adjustment for clinical parameters proven to be predictive of complications in CAD patients, such as ankle-brachial index, heart rate and CAD duration. Interestingly, when levels of both IF1 and apoA-I were high, mortality was much lower than when only one of these was high. Conclusions: IF1 is a new biological marker strongly predictive of mortality in CAD patients. Among patients with normal or elevated apoA-I levels, IF1 measurement may help to identify those who are at low risk of complications and those who are not. IF1 measurement could be use in a panel of other emerging biomarkers that have been proven to be better than HDL-C level, for the better assessment of cardiovascular risk or in the setting of pharmacotherapy.

Background Epidemiological and observational studies have established that high-density lipoprotein cholesterol (HDL-C) is an independent negative cardiovascular risk factor. However, simple measurement of HDL-C levels is no longer sufficient for cardiovascular risk assessment. Therefore, there is a critical need for novel non-invasive biomarkers that would display prognostic superiority over HDL-C. Cell surface ecto-F1-ATPase contributes to several athero-protective properties of HDL, including reverse cholesterol transport and vascular endothelial protection. Serum inhibitory factor 1 (IF1), an endogenous inhibitor of ecto-F1-ATPase, is an independent determinant of HDL-C associated with low risk of coronary artery disease (CAD). This work aimed to examine the predictive value of serum IF1 for long-term mortality in CAD patients. Its informative value was compared to that of HDL-C. Method Serum IF1 levels were measured in 577 male participants with stable CAD (age 45–74 years) from the GENES (Genetique et ENvironnement en Europe du Sud) study. Vital status was yearly assessed, with a median follow-up of 11 years and a 29.5 % mortality rate. Cardiovascular mortality accounted for the majority (62.4 %) of deaths. Results IF1 levels were positively correlated with HDL-C (rs = 0.40; P

OBJECTIVE The value of exercise testing (ET) in asymptomatic subjects remains controversial and is unknown in countries with a low coronary heart disease (CHD) incidence. The aim of this study was to investigate the ability of ET to improve the prediction of a first coronary event in such a population. METHODS Using a prospective cohort study, 1051 consecutive healthy asymptomatic adults were enrolled in a cardiovascular screening program including ET. The pre-test risk of CHD was evaluated by the 10-year Framingham risk function. Positive ET was defined as a horizontal or downsloping ST-segment depression >/=1.0 mm. The primary outcome was total coronary events (CE) occurrence, including cardiac deaths, acute myocardial infarction and stable or unstable angina. The mean follow-up period was 6 years. RESULTS Subjects were aged 18-79 years and 36% were women. A total of 89 subjects (8.5%) had a positive ET. Positive exercise testing was associated with CE occurrence in a univariate analysis only in subjects with higher pre-test risk, defined by a 10-year Framingham risk >10.4% [hazards ratio (HR)=2.61; 95% confidence interval (CI) (1.07-6.40)]. In this risk category, ET was able to provide incremental information over the major risk factors in both men and women [risk factor-adjusted HR for positive ET=2.86; 95% CI (1.14-7.20)]. This risk excess in subjects with positive ET persisted even when a coronary revascularization was performed. Subjects with intermediate pre-test probability (10-15%) and positive ET had a post-test probability of CE largely equivalent to the probability in subjects with known CHD. CONCLUSION Additional information provided by ET in subjects with a pre-test risk at 10-years >10% should lead to a more efficient use of risk-reducing therapies than it would be the case in this risk category with the analysis of traditional risk factors only.

BackgroundThe 2012 ESC guidelines recommend a LDL-cholesterol (LDL-C) lower than 3mmol/L for subjects at low or moderate risk with a class I/A and a strong grade. According to ESC, statins should be used as the drugs of first choice. The aim of this study was to assess the association between elevated LDL-C with total and cardiovascular (CV) mortality in primary prevention.MethodsOur study population consisted in patients who had been admitted from 1995 to 2011 in a preventive cardiology unit of a large French university hospital. We excluded patients whose age was less than 30 and all patients with previous ischemic heart disease. Vital status in 2011 was checked through the death national database.Results4885 patients were included (59% men; 53±10 yrs). After a mean follow-up of 8.6 years, 129 deaths, including 31 CV deaths, were recorded. The mean LDL-C was 3.98±1.18mmol/L (3.90 in men and 4.11 in women). Among these 4885 patients, 2648 (54.2%) had LDL-C lower than 4mmol/L, 1890 (38.7%) had LDL-C between 4 and 6mmol/L, 347 (7.1%) had LDL-C higher than 6mmol/L, and 1833 (37.5%) were on current lipid-lowering treatment. After adjustment for age, gender, smoking, hypertension and diabetes, an increased LDL-C > 4mmol/L was significantly associated with all cause mortality (hazard ratio (HR) 2.06; 95% confidence interval (CI) [1.42-3.00], p=0.001) and with CV mortality (HR 2.18; 95% CI [1.04-4.57], p=0.04). After adjustment for these classical risk factors and for lipid-lowering treatment, LDL-C remained significantly associated with an increasing risk of all cause mortality; with LDL-C < 4mmol/L as a reference class, LDL-C levels between 4 and 6mmol/L were associated with an increased all cause mortality (HR 1.72; 95% CI [1.17-2.54], p=0.006) as well as LDL-C > 6mmol/L (HR 2.60; 95% CI [1.49-4.85], p=0.001).ConclusionsLDL-C levels higher than 4mmol/L were significantly associated with all-cause and cardiovascular mortality in primary prevention.

OBJECTIVES: Relationship between hepatic lipase (LIPC) polymorphism and coronary artery disease (CAD) has often led to contradictory results. We studied this relation by genotyping rs1800588 in the LIPC promoter in a case-control study on CAD (the GENES study). We also investigated the relationship between this polymorphism and the ankle-brachial index (ABI), which is predictive of atherosclerosis progression and complications in patients at high cardiovascular risk. METHODS: 557 men aged 45-74 with stable coronary artery disease and 560 paired controls were genotyped for rs1800588. Medical data, clinical examination including determination of ABI and biological measurements related to cardiovascular risk factors enabled multivariate analyses and multiple adjustments. RESULTS: CAD cases showed a higher T-allele frequency than controls (0.246 vs 0.192, p = 0.003). An interaction has been found between LIPC polymorphism and triglycerides (TG) levels regarding risk of CAD: TT-homozigosity was associated with an Odds ratio (OR) of 6.4 (CI: 1.8-22.3) when TG were below 1.5 g/L, but no association was found at higher TG levels (OR = 1.34, CI: 0.3-5.9). The distribution of LIPC genotypes was compared between CAD patients with normal or abnormal ABI and impact of LIPC polymorphism on ABI was determined. Following multiple adjustments, association of the T-allele with pejorative ABI (

Objective— Despite cardioprotective properties, studies investigating adiponectin as a cardiovascular disease marker led to conflicting results. We investigated in participants with stable coronary artery disease (CAD) and controls whether serum adiponectin was associated with long-term mortality, considering varying degrees of CAD severity. Methods and Results— A case–control design with prospective median follow-up of 8.1 years was used. Survival rates among 715 CAD men (aged 45–74 years) in increasing quartiles of serum adiponectin values were 87.5%, 85.6%, 76.4%, and 67.6%, respectively ( P P =0.035). Adiponectin concentration above the highest quartile was associated with an increased risk of total and cardiovascular disease mortality in CAD patients ( P =0.001 and P =0.001) and controls ( P =0.02 and P =0.004). The associations among high adiponectin, total mortality, and cardiovascular disease mortality remained significant after multivariate adjustments for metabolic, cardiac, and CAD severity variables. No significant interaction was found among CAD patients, controls, and the relationship of adiponectin with mortality. Conclusion— High serum adiponectin is a predictor of mortality, particularly from cardiovascular disease. This prognostic value remains significant whatever the severity of the CAD and the metabolic status and is not different among people with and without CAD.

International audience; HDL is strongly inversely related to cardiovascular risk. Hepatic HDL uptake is controlled by ecto-F1-ATPase activity, and potentially inhibited by mitochondrial inhibitor factor 1 (IF1). We recently found that IF1 is present in serum and correlates with HDL-cholesterol (HDL-C). Here, we have evaluated the relationship between circulating IF1 and plasma lipoproteins, and we determined whether IF1 concentration is associated with the risk of coronary heart disease (CHD). Serum IF1 was measured in 648 coronary patients ages 45-74 and in 669 matched male controls, in the context of a cross-sectional study on CHD. Cardiovascular risk factors were documented for each participant, including life-style habits and biological and clinical markers. In controls, multivariate analysis demonstrated that IF1 was independently positively associated with HDL-C and apoA-I (r = 0.27 and 0.28, respectively, P < 0.001) and negatively with triglycerides (r = -0.23, P < 0.001). Mean IF1 concentration was lower in CHD patients than in controls (0.43 mg/l and 0.53 mg/l, respectively, P < 0.001). In multivariate analyses, following adjustments on cardiovascular risk factors or markers, IF1 was negatively related to CHD (P < 0.001). This relationship was maintained after adjustment for HDL-C or apoA-I. This study identifies IF1 as a new determinant of HDL-C that is inversely associated with CHD.

The prognostic value of symptomatic peripheral arterial disease (PAD) in patients with coronary heart disease (CHD) is well documented, but few reports differentiating between symptomatic and asymptomatic forms of PAD are available. We investigated the respective prognostic effect of clinical and subclinical PAD on long-term all-cause mortality in patients with stable CHD. We analyzed 710 patients with stable CHD referred for hospitalization for CHD evaluation and management. As a part of the study, they completed questionnaires on medical history, underwent a standardized clinical examination, including ankle-brachial index (ABI) measurement, and provided a fasting blood sample. Three groups of patients were individualized: no PAD (no history of PAD and ABI >0.9 but ≤1.4); subclinical PAD (no history of PAD but abnormal ABI [i.e., ≤0.9 or >1.4); and clinical PAD (history of claudication, peripheral arterial surgery, or amputation due to PAD). Clinical and subclinical PAD was present in 83 (11.7%) and 181 (25.5%) patients, respectively. After a median follow-up of 7.2 years, 130 patients died. On multivariate analysis adjusted for age, hypertension, diabetes, dyslipidemia, smoking, left ventricular ejection fraction, CHD duration, heart rate, history of stroke or transient ischemic attack, and coronary revascularization, previous clinical PAD (hazard ratio 2.11, 95% confidence interval 1.28 to 3.47) and subclinical PAD (hazard ratio 1.65, 95% confidence interval 1.11 to 2.44) were significantly associated with increased all-cause mortality. In conclusion, our study has demonstrated that the detection of subclinical PAD by ABI in patients with stable CHD provides additional information for long-term mortality risk evaluation.

One of the imaging tests most commonly used to assess cardiovascular diseases (CVDs) in daily practice is Doppler ultrasonography of the carotid and femoral arteries. We included 2709 participants with no history or symptoms of CVD; they had a risk factor assessment and a carotid and femoral ultrasonography at baseline. Incident cases of definite coronary events were recorded during a median follow-up of 6 years. Approximately, 63% of the sample presented abnormalities (carotid stenosis >50%, carotid plaque, femoral plaque, increased intima–media thickness [IMT]). A moderately increased IMT (>0.63 mm) or the presence of carotid or femoral artery plaque was related to prognosis. The associations persisted after adjustment for pretest risk, treatment with statins, and other Doppler ultrasonography abnormalities. The hazard ratio increased significantly with the number of abnormalities (varying from 2.35 [1.16-4.74] to 14.83 [6.47-33.9]).

SummaryBackgroundChronic obstructive pulmonary disease (COPD) and cardiovascular diseases (CVD) share risk factors and impair each other's prognosis.AimsTo assess the prevalence of airflow limitation (AL) compatible with COPD in a population at cardiovascular risk and to identify determinants of AL.MethodsAll consecutive patients referred to the cardiovascular prevention unit of a university hospital in 2009 were studied in a cross-sectional analysis. Patients answered questionnaires on socioeconomic status, medical history and lifestyle, and underwent extensive physical examinations, biological measures and spirometry testing. AL was defined as FEV1/FVC20%) for 10%. Prevalence of AL was 5.9% (95% confidence interval [CI] 4.0–8.3%) in the whole population and 4.3% (2.6–6.6%) among subjects in primary cardiovascular prevention. AL was independently associated with CVD (adjusted odds ratio 4.18, 95% CI 1.72–10.15; P=0.002) but not with Framingham CHD risk. More than 80% of patients screened with AL had not been diagnosed previously and more than one in two patients was asymptomatic.ConclusionPatients with CVD are at increased risk of AL and thus should benefit from AL screening as they are frequently asymptomatic.

Metabolic syndrome is associated with an increased risk of coronary heart disease (CHD), but it is still debated whether it could act as an independent risk factor per se. We compared the respective values of metabolic syndrome and its components to predict presence of CHD. Methods A case control study was conducted in 2001–2004, including 748 cases (French male patients with a history of CHD) and 810 controls from the general population. Data on medical history and cardiovascular risk factors were collected. Two logistic regression models were built to predict the probability to be a case (to have CHD). The first one considered metabolic syndrome as explanatory variable. In the second one, metabolic syndrome was replaced by its components (high blood pressure or antihypertensive drug use, waist circumference, high glycemia or hypoglycemic drug use, plasma triglycerides and HDL-cholesterol). Both models were adjusted for age, level of education, physical activity, smoking and LDL-cholesterol. Results Participants were aged 45–75 years old, 45.4% of cases and 18.6% of controls had a metabolic syndrome. The sensitivity and the specificity of the first model to predict CHD were 81% and 62%, respectively, and the c-statistic reached 0.79 [95% CI: 0.76–0.80]. In the second model, sensitivity, specificity and c-statistic were 82%, 67% and 0.85 [0.83–0.86], thus leading to a better discrimination. Among cases, 5.6% were adequately reclassified by the second model (0.7% non adequately reclassified). Among controls, 16.3% were adequately reclassified, without any wrong reclassification. Overall, the second model led to an improved net reclassification of 4.9% in cases and 16.3% in controls, compared to the first model. Conclusions Using the components of the metabolic syndrome in algorithms to predict presence of CHD is better than using metabolic syndrome as a whole entity. This result should improve the screening of people who are likely to suffer from silent CHD.

Background The choice of noninvasive tests used in primary prevention of cardiovascular diseases must be based on medical evidence. The aim of this study was to assess the additional prognostic value, over conventional risk factors, of physical examination, exercise testing, and arterial ultrasonography, in predicting a first coronary event. Methods A prospective cohort study was conducted between 1996 and 2004 (n = 2,709), with follow-up in 2006 (response rate 96.6%). Participants had no history or symptoms of cardiovascular disease and had a standardized physical examination, a cardiac exercise testing, and carotid and femoral ultrasonography at baseline. Incident cases of definite coronary events were recorded during follow-up. Results Over the Framingham risk score, femoral bruit, positive exercise test, intima-media thickness >0.63 mm, and a femoral plaque provided significant additional information to the prediction model. The addition of the exercise test to the traditional risk factors, then the intima-media thickness and lastly the presence of femoral plaques, produces incremental increases in the area under the receiver operating characteristic curve (0.73-0.78, P = .02) and about a 50% increase in the positive predictive value (15.8%-31.4%), with no effect on the negative predictive value (96.4%-96.9%). Conclusion Physical examination, exercise testing, and arterial ultrasonography provide incremental information on the risk of coronary event in asymptomatic adults. Exercise testing and femoral ultrasonography also improve the accuracy of the risk stratification.

Metabolic syndrome is associated with an increased risk of coronary heart disease (CHD), but it is still debated whether it could act as an independent risk factor per se. We compared the respective values of metabolic syndrome and its components to predict presence of CHD. Download : Download full-size image Seasonal variations of HRV Methods A case control study was conducted in 2001–2004, including 748 cases (French male patients with a history of CHD) and 810 controls from the general population. Data on medical history and cardiovascular risk factors were collected. Two logistic regression models were built to predict the probability to be a case (to have CHD). The first one considered metabolic syndrome as explanatory variable. In the second one, metabolic syndrome was replaced by its components (high blood pressure or antihypertensive drug use, waist circumference, high glycemia or hypoglycemic drug use, plasma triglycerides and HDL-cholesterol). Both models were adjusted for age, level of education, physical activity, smoking and LDL-cholesterol. Results Participants were aged 45–75 years old, 45.4% of cases and 18.6% of controls had a metabolic syndrome. The sensitivity and the specificity of the first model to predict CHD were 81% and 62%, respectively, and the c-statistic reached 0.79 [95% CI: 0.76–0.80]. In the second model, sensitivity, specificity and c-statistic were 82%, 67% and 0.85 [0.83–0.86], thus leading to a better discrimination. Among cases, 5.6% were adequately reclassified by the second model (0.7% non adequately reclassified). Among controls, 16.3% were adequately reclassified, without any wrong reclassification. Overall, the second model led to an improved net reclassification of 4.9% in cases and 16.3% in controls, compared to the first model. Conclusions Using the components of the metabolic syndrome in algorithms to predict presence of CHD is better than using metabolic syndrome as a whole entity. This result should improve the screening of people who are likely to suffer from silent CHD.

An insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) has been associated with an increased risk of coronary artery disease (CAD) and myocardial infarction (MI). However, this finding has not been fully investigated in European populations with very low CAD risk. In a case-control study on a population from Southern Europe (Toulouse, France), we evaluated the ACE I/D polymorphism in 405 men, aged 35-65 years, who underwent coronary angiography and in 357 representative control men within the same age range. We also explored associations in the patients between this polymorphism and CAD severity. The ACE genotype was not associated with the presence of either CAD or MI. The ACE genotype was not a marker for angiographically assessed CAD severity. In a sample in one of the European populations with the lowest CAD risk, ACE I/D polymorphism was not associated with an increased risk for CAD or MI and did not influence the extent of CAD.

Purpose Chronic Obstructive Pulmonary Disease (COPD) is expected to be the third cause of mortality in the world in 2020. Paradoxically, this disease is widely underdiagnosed and its prevalence remains relatively unknown, in particular in people at cardiovascular risk for whom the association with COPD may worsen the prognosis. The aim of this study was to assess COPD prevalence in a population at cardiovascular risk and to analyse determinants of COPD. Methods Our study was based on patients referred for cardiovascular check-up to a Preventive Cardiology Clinic in a University Hospital in 2009. Participants answered to questionnaires on socio-economic level, medical history and life style. They completed an extensive physical examination and a spirometry test. COPD prevalence was based on the spirometric classification proposed by the Global Initiative for chronic Obstructive Lung Disease. Determinants of COPD were assessed with logistic regression. Results The sample comprised 502 participants (mean age: 57.4 ± 11.1 years), including 60% of men, 17% of current smokers, 42% of former smokers and 10% of patients with a history of cardiovascular disease (ischemic heart disease, cerebrovascular or peripheral arterial disease). Ten-year risk of coronary heart disease according to the Framingham equation was intermediate (10–20%) for 33% of patients and high (> 20%) for 5%. After exclusion of asthmatic patients, 5.8% [95% CI: 3.9% – 8.2%] were spirometrically screened as COPD patients (Forced Expiratory Volume in one second/Forced Vital Capacity Conclusion Patients with cardiovascular disease are at increased risk of COPD and thus should beneficiate from COPD screening.

ObjectivesThis study assessed the accuracy of the screening vascular physical examination for predicting asymptomatic peripheral arterial disease (PAD) or subclinical atherosclerosis in asymptomatic and apparently healthy subjects.MethodsA standardized physical examination and a carotid and femoral ultrasonography were administered to 2736 men and women aged 20 to 90 years old, with no personal history of cardiovascular disease (CVD) and no complaint of neurologic, coronary, or lower limb symptom. We assessed the accuracy of auscultation for bruits and pulse palpation for identifying the presence of significant carotid stenosis, carotid plaque, femoral plaque, and ankle-brachial index (ABI)

SummaryBackgroundCigarette smoking, raised blood pressure, unfavourable lipid concentrations, diabetes and – more indirectly – obesity, are responsible for most coronary heart disease events in developed and developing countries.AimsThe objective of our study was to compare prevalence, treatment and control of cardiovascular risk factors in two samples of men with stable coronary heart disease, recruited in France and Spain.MethodsStandardized measurements of body mass index, systolic and diastolic blood pressures, plasma lipids, glycaemia, and smoking were collected and drug use was registered. Cross-sectional comparisons were made between French and Spanish samples.ResultsData from 982 individuals were analysed (420 French and 562 Spanish men). Current smoking was more frequent in Spain (p

BackgroundResting heart rate (RHR) is known as a cardiovascular risk factor (RF), correlated with hypertension, cardiac failure and coronary artery disease. The aim of this study was to assess the risk of all-cause mortality in a general population in a prediction algorithm including RHR as an independent parameter.MethodsOur study population consisted in patients, both women and men, who had consulted from 1995 to 2011 to the Department of Preventive Cardiology (DPC) in a Southwestern French University Hospital. We excluded patients whose age was less than 30 years old and all patients with established history of ischemic heart disease. An algorithm for prediction of risk of mortality in primary prevention was built using Kaplan-Meier statistic and a Cox proportional hazards model.Results4885 patients were included. 56% were men and the mean age was 53. After a mean follow up of 8.6 years, 129 deaths were recorded. In multivariate analysis, independent RF were age (Hazard Ratio (HR)=1.06, p4 mmol/L (HR=2.04, p 65 bpm (HR=1.54, p=0.02, 95% CI [1.06-2.24]). A good calibration was obtained (p value NS for Hosmer-Lemeshow %2 test). The median predicted risk of mortality was 6.52% and was not significantly different to the observed risk of all cause mortality (6.60%; 95%CI [5.22%-8.34%]).ConclusionsRHR can be used to predict all-cause mortality in primary prevention and might be evaluated as a simple predictive tool in current practice.

PurposeCurrent guidelines recommend lowering LDL-cholesterol below 2.6 mmol/L in patients with established cardiovascular disease. The potential benefit of an additional decrease in LDL-cholesterol has been suggested for coronary heart disease patients with diabetes or dysmetabolic profile, as they are at high risk of recurrence. The aim of this analysis was to estimate the proportion of patients with poor metabolic profile among those with established coronary heart disease.MethodsA sample of French male patients with a history of acute coronary syndrome was recruited from 2001 to 2004. Those with recent (in the past two months) acute coronary syndrome were excluded.ResultsThe sample comprised 824 men. Mean age was 60.3 years (standard deviation: 7.9), 22% of patients were still current smokers and 65% had high blood pressure (≥ 140/90 or 130/80 mmHg if diabetes). Diabetes was encountered in 32% of patients (20%, 36% and 38% from the 10-year age group 45-54 to 65-74 years, respectively, p