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Few studies have analyzed the relationship between glucose variability (GV) and adverse health outcomes in patients with differences in glycemic status. The present study tests the hypothesis that GV predicts all-cause mortality regardless of glycemic status after simple adjustment (age and sex) and full adjustment (age, sex, cardiovascular disease, hypertension, use of aspirin, statins, GLP-1 receptor agonists, SGLT-2 inhibitors and DPP-4 inhibitors, baseline FPG and average HbA1c). Methods Prospective cohort study with 795 normoglycemic patients, 233 patients with prediabetes, and 4,102 patients with type 2 diabetes. GV was measured using the coefficient of variation of fasting plasma glucose (CV-FPG) over 12 years of follow-up. The outcome measure was all-cause mortality. Results A total of 1,223 patients (657 men, 566 women) died after a median of 9.8 years of followup, with an all-cause mortality rate of 23.35/1,000 person-years. In prediabetes or T2DM patients, the fourth quartile of CV-FPG exerted a significant effect on all-cause mortality after simple and full adjustment. A sensitivity analysis excluding participants who died during the first year of follow-up revealed the following results for the highest quartile in the fully adjusted model: overall, HR (95%CI) = 1.54 (1.26–1.89); dysglycemia (prediabetes and T2DM), HR = 1.41 (1.15–1.73); T2DM, HR = 1.36 (1.10–1.67). Conclusion We found CV-FPG to be useful for measurement of GV. It could also be used for the prognostic stratification of patients with dysglycemia, This study was funded by Instituto de Salud Carlos III through projects “PI15/00259” and “PI18/01025” and co-funded by the European Regional Development Fund,“A way of shaping Europe”. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Objetivo: El objetivo de este estudio fue analizar la relación entre el colesterol-HDL y el riesgo de infección por SARS-CoV-2 en mayores de 75 años residentes en la Comunidad de Madrid. Métodos: Estudio de una cohorte de base poblacional, compuesto por todos los residentes en Madrid (España) nacidos antes del 1 de enero de 1945 y vivos el 31 de diciembre de 2019. Los datos demográficos, clínicos y analíticos se obtuvieron de las historias clínicas electrónicas de atención primaria desde enero de 2015. La infección confirmada por SARS-CoV-2 se definió como un resultado positivo en la RT-PCR o en la prueba de antígeno. Los datos sobre infección por SARS-CoV-2 corresponden al periodo del 1 de marzo de 2020 hasta el 31 de diciembre de 2020. Resultados: De los 593.342 participantes de la cohorte, 501.813 tenían al menos una determinación de colesterol-HDL en los últimos 5 años. Su edad media era 83,4 ± 5,6 años y el 62,4% eran mujeres. Un total de 36.996 (7,4%) tuvieron una infección confirmada por SARS-CoV2 durante el año 2020. El riesgo de infección [odds ratio (intervalo de confianza 95%)] por SARS-CoV2 según los quintiles crecientes de colesterol-HDL fue de 1, 0,960 (0,915-1,007), 0,891 (0,848-0,935), 0,865 (0,824-0,909) y 0,833 (0.792-0,876), tras ajustar por edad, sexo, factores de riesgo cardiovascular y comorbilidades. Conclusiones: Existe una relación inversa y dosis-dependiente entre la concentración de colesterol-HDL y el riesgo de infección por SARS-CoV2 en los mayores de 75 años de la Comunidad de Madrid.

Aims Nonagenarians are a fast growing segment of industrialized countries' populations. Despite a greater risk of cardiovascular disease, there are limited data about their use of preventive therapies and factors guiding decisions regarding their prescription. The aim of this study was to evaluate the prevalence of cardiovascular diseases and the patterns of use of cardiovascular treatments in subjects ≥90 years old. Methods Population-based, cross-sectional study, in all nonagenarians residing in the Community of Madrid (Spain). Data were obtained from their electronic clinical records in primary care. Results Data were available from 59,423 subjects (mean age 93.3 years, 74.2% female, 13.5% with dementia). Prevalence of cardiovascular disease was 24.1% (10.9% with coronary artery disease (CAD), 13.1% with cerebrovascular disease (CVD) and 2.7% with peripheral artery disease(PAD)). In primary prevention, the use of statins and antiplatelet agents was 21.9% and 26.7%, respectively. Of subjects with vascular disease 27.7% were receiving a combined preventive strategy (use of antithrombotics, plus statins, plus blood pressure below 140/90 mmHg). Factors favourably associated with a combined preventive strategy were: female sex (odds ratio (OR) 1.29; 95% confidence interval (CI): 1.11–1.49), being independent versus totally dependent (OR 1.94; 95% CI: 1.43–2.65), diabetes (OR 1.42; 95% CI: 1.20–1.68), and negatively, age (OR 0.87; 95% CI: 0.85–0.90), CVD versus CAD (OR 0.41; 95% CI: 0.35–0.47), PAD versus CAD (OR 0.23; 95% CI: 0.18–0.30), dementia (OR 0.61; 95% CI: 0.49–0.76) and nursing home residency (OR 0.73; 95% CI: 0.57–0.93). Conclusion Nonagenarians have a great burden of cardiovascular diseases and receive a great number of preventive therapies, even in primary prevention, despite their unproven efficacy at these ages.

The presence of erectile dysfunction (ED) could be a warning of vascular disease in different arterial territories.The aim of this study was to investigate the association between ED and the presence of atherosclerosis in 2 different vascular beds: carotid and lower limbs.A total of 614 volunteers between 45 and 74 years of age (mean age 61.0 years) were randomly selected from the general population. ED was assessed using the International Index of Erectile Function (IIEF-5). Ankle-brachial index (ABI) measurement and carotid atherosclerosis were evaluated by echo-Doppler.Mean carotid intima-media thickness (IMT), prevalence of carotid plaques, mean ABI, and prevalence of ABI0.9 were the main outcome measures.ED was present in 373 subjects (59.7%). Mean carotid IMT was significantly higher in men with ED (0.762 ± 0.151 mm vs 0.718 ± 0.114 mm, P.001). Also the global prevalence of carotid plaques was more frequent in men with ED (63.8% vs 44.8%, P.001), even after adjusting by age, cardiovascular risk factors, and ongoing treatment (P = .039). Both the IMT and the prevalence of carotid plaques increased significantly with ED severity (P trend .004 and.001, respectively). There were no significant differences between groups neither in mean ABI nor in the prevalence of subjects with ABI0.9. However, there was a trend to a lower ABI and a higher prevalence of ABI0.9 with increasing ED severity.In the general population, the presence of ED identifies subjects with higher atherosclerosis burden in carotid arteries but not in the lower extremities.

Familial hypercholesterolemia is an autosomal dominant disease of lipid metabolism caused by defects in the genes LDLR, APOB, and PCSK9. The prevalence of heterozygous familial hypercholesterolemia (HeFH) is estimated between 1/200 and 1/250. Early detection of patients with FH allows initiation of treatment, thus reducing the risk of coronary heart disease. In this study, we performed in vitro characterization of new LDLR variants found in our patients. Genetic analysis was performed by Next Generation Sequencing using a customized panel of 198 genes in DNA samples of 516 subjects with a clinical diagnosis of probable or definitive FH. All new LDLR variants found in our patients were functionally validated in CHO-ldlA7 cells. The LDLR activity was measured by flow cytometry and LDLR expression was detected by immunofluorescence. Seven new variants at LDLR were tested: c.518 G>C;p.(Cys173Ser), c.[684 G>T;694 G>T];p.[Glu228Asp;Ala232Ser], c.926C>A;p.(Pro309His), c.1261A>G;p.(Ser421Gly), c.1594T>A;p.(Tyr532Asn), and c.2138delC;p.(Thr713Lysfs*17). We classified all variants as pathogenic except p.(Ser421Gly) and p.(Ala232Ser). The functional in vitro characterization of rare variants at the LDLR is a useful tool to classify the new variants. This approach allows us to confirm the genetic diagnosis of FH, avoiding the classification as "uncertain significant variants", and therefore, carry out cascade family screening.

Background and aims Autosomal recessive hypercholesterolemia (ARH) is a rare disorder caused by mutations in LDLRAP1, which impairs internalization of hepatic LDL receptor (LDLR). ARH patients respond relatively well to statins or the combination of statins and Ezetimibe, but scarce and variable data on treatment with PCSK9 inhibitors is available. We aimed to identify and characterize the defect in a hypercholesterolemic patient with premature cardiovascular disease and determine the response to lipid-lowering treatment. Methods and results Gene sequencing revealed a homozygous c.1A > G:p.? variant in LDLRAP1. Primary lymphocytes were isolated from the ARH patient, one control and two LDLR-defective subjects, one LDLR:p.(Cys352Ser) heterozygote and one LDLR:p.(Asn825Lys) homozygote. The patient had undetectable full-length ARH protein by Western blotting, but expressed a lower-than-normal molecular weight peptide. LDLR activity was measured by flow cytometry, which showed that LDL binding and uptake were reduced in lymphocytes from the ARH patient as compared to control lymphocytes, but were slightly higher than in those from the LDLR:p.(Cys352Ser) heterozygote. Despite the analogous internalization defect predicted in ARH and homozygous LDLR:p.(Asn825Lys) lymphocytes, LDL uptake was higher in the former than in the latter. LDL-cholesterol levels were markedly reduced by the successive therapy with Atorvastatin and Atorvastatin plus Ezetimibe, and the addition of Evolocumab biweekly decreased LDL-cholesterol by a further 39%. Conclusions The LDLRAP1:c.1A > G variant is associated with the appearance of an N-terminal truncated ARH protein and to reduced, although still significant, LDLR activity in lymphocytes. Residual LDLR activity may be relevant for the substantial response of the patient to Evolocumab.

The objective of the present study was to evaluate the prevalence of atrial fibrillation (AF) in nonagenarians living in the Community of Madrid, their clinical features, the use of anticoagulant therapy and factors associated with its use.This was a cross-sectional study of 59 423 individuals aged ≥90 years, living in the Community of Madrid on 31 December 2015. Clinical information was obtained from a database that includes information from electronic medical records collected by 3881 general practitioners in primary care.Some 16.95% of nonagenarians (n = 10 077) were diagnosed with atrial fibrillation. These individuals have a higher prevalence of classic risk factors and established cardiovascular disease, as well as higher comorbidity. Of these, 67.6% received anticoagulant therapy, 27.9% received antiplatelet agents and 7.2% received both treatments simultaneously. Of the participants administered anticoagulation, 11.6% received a direct oral anticoagulant. The use of anticoagulant therapy was associated with a younger age, the presence of heart failure or venous thromboembolism, the absence of hypertension, a higher Barthel Index score, a greater number of prescribed drugs, a higher body mass index and a lower Charlson Comorbidity Index score.Nonagenarians with atrial fibrillation have a high risk of stroke; however, high comorbidity and functional impairment have limited the use of anticoagulant therapy. Geriatr Gerontol Int 2019; 19: 203-207.

Background The R46L variant of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene has been related to lipid levels and cardiovascular disease. Objective To evaluate the influence of this polymorphism on subclinical vascular disease and erectile dysfunction (ED). Methods We analyzed the association of the PCSK9 rs11591147 single-nucleotide polymorphism with lipid levels, intima-media thickness (IMT), and the ankle-brachial index, in 1188 adults free of cardiovascular disease, randomly selected from the population. In 473 male participants, we also investigated its relationship with ED. The association of the R46L polymorphism with lipid levels was also assessed in 2 cohorts of 1103 prepuberal children and 830 adolescents. Results The prevalence of the T allele was 2.9% in adults. Low-density lipoprotein cholesterol (LDL-cholesterol) levels did not vary according to this polymorphism (134 ± 32 vs 134 ± 31 mg/dL, for the TT + GT vs GG carriers, respectively, P = .931). Despite equal LDL-cholesterol levels, adults carrying the T allele had a lower mean common carotid IMT (0.685 ± 0.09 vs 0.723 ± 0.127 mm; P = .035), a lower maximum common carotid IMT (0.819 ± 0.11 vs 0.865 ± 0.159 mm; P = .040), and, in males, a lower prevalence of ED (36.8% vs 61%: P = .036), than GG carriers. Prevalence of the T allele was 3.2% in both cohorts of children. They had lower levels of LDL-cholesterol than GG subjects (100 vs 109 mg/dL; P = .060, for prepuberal children, and 85 vs 99 mg/dL; P = .010 for adolescents). Conclusion In our population, an association between the PCSK9 R46L variant and LDL-cholesterol levels is observed in children. In adults, although its association with lipid levels is not evident, there is a significant relationship between the PCSK9 R46L variant and markers of subclinical atherosclerosis, including IMT and ED.

Women have a higher morbidity and mortality than men after an acute coronary event. We analyzed the prescription rates of evidence-based pharmacological therapies for patients with stable coronary heart disease and whether there were any differences with respect to gender.This cross-sectional study evaluated 8817 patients, 26.3% women, receiving attention from 1799 family doctors in primary care centers (PCC) throughout Spain, and who had had a coronary event requiring hospitalization in the previous 6 months to 10 years.Mean age was 65.4 years and a mean time-lapse since hospitalization of 37.4 months. In the overall population, prescription medications were: antiplatelet drugs in 80.5% of patients, 79% statins, 66% blockers of the angiotensin-renin system (BARS) and 47% beta-blockers. Males received less cardiovascular disease medications than females (4.3+/-1.5 versus 4.6+/-1.6, respectively; p0.001), but when adjusted for risk factors the significance was lost (p=0.231). Following adjustment for risk factors and for co-morbidities, the use of diuretics was significantly higher in women while beta-blockers and statins were higher in men. The triple combination of antithrombotics, beta-blockers and statins was used in 41.4% (43.8% males versus 34.6% females; p0.001) while 24.3% used this triple combination plus a BARS; without significant difference between the genders.An important percentage of patients with stable coronary disease, particularly women, attended-to in primary care do not receive medications that have been shown to decrease the morbido-mortality of cardiovascular disease.

To investigate some individual and genetic factors that may influence the response of low-density lipoprotein cholesterol (LDL-C) to pravastatin treatment, we recruited 440 subjects with hypercholesterolemia (mean age, 57 years; 43% men) from 21 primary health care centers-outpatient clinics into a prospective, multicentered intervention trial. Pravastatin (20 mg/d) was prescribed for 16 weeks. The main outcome was the percentage variation in LDL-C concentration relative to baseline. Blood analyses and genotyping were performed centrally. The results indicated that LDL-C decreased by 20.5% (range, +21% to -66%) after pravastatin treatment. Baseline concentration of LDL-C (the higher the concentration, the greater the decrease), lipoprotein (a) levels (the lower the concentration, the greater the response), and Ava II polymorphism of the LDL-receptor gene significantly influenced the hypolipemic effect ( P.001, P = .014, and P = .004, respectively). These 3 factors combined explained 10.6% of the variation in LDL-C response. Age, sex, smoking habit, alcohol consumption, body mass index, and apolipoprotein E genotype had no significant effect on response. We conclude that baseline levels of LDL-C and lipoprotein (a) together with the Ava II polymorphism of the LDL-receptor gene have a significant influence on the LDL-C response to pravastatin treatment in patients monitored in a standard primary health care outpatient clinic setting.

Statins decrease cardiovascular morbidity and mortality, essentially, by reducing LDL-cholesterol levels and, additionally, by increasing HDL-cholesterol concentrations. Environmental and genetic factors are known to affect LDL-C response to statins but less is known regarding HDL-C. We have evaluated the lipid and lipoprotein response to 20 mg/day of pravastatin for 16 weeks in relation to the G/A polymorphism in the promoter region of the apo A-I gene in 397 hypercholesterolaemic subjects followed-up on an out-patient basis. In the study population, 61.7% were homozygous for the G allele and 36% were heterozygous. The A allele carriers had an HDL-C 6.5% higher than the G allele homozygotes (P=0.021 in univariate analysis; P=0.009 in multivariate analysis). However, on segregation by gender and smoking status the effect was significant only in non-smoking males. The A allele carriers did not increase their HDL-C concentrations after treatment (-0.3, 95%CI -3.3 to 2.7%) while G allele homozygotes had a 4.9% increase (95%CI 2.5-7.3%). Differences in the response between both groups were significant before (P=0.008) and after adjustment for confounding variables such as age and baseline HDL-C concentration (P=0.046). We conclude that the G/A polymorphism of the apo A-I promoter region affects not only baseline HDL-C concentrations but also its response to pravastatin treatment.

OBJECTIVES We sought to evaluate whether pravastatin treatment increases myocardial perfusion, as assessed by thallium-201 single-photon emission computed tomographic (SPECT) dipyridamole testing, in patients with coronary artery disease (CAD) and average cholesterol levels. BACKGROUND Previous studies in hypercholesterolemic patients have demonstrated that cholesterol reduction restores peripheral and coronary endothelium-dependent vasodilation and increases myocardial perfusion. METHODS This was a randomized, placebo-controlled study with a cross-over design. Twenty patients with CAD were randomly assigned to receive 20 mg of pravastatin or placebo for 16 weeks and then were crossed over to the opposite medication for a further 16 weeks. Lipid and lipoprotein analysis and dipyridamole thallium-201 SPECT were performed at the end of each period. The SPECT images were visually analyzed in eight myocardial segments using a 4-point scoring system by two independent observers. A summed stress score and a summed rest score were obtained for each patient. Quantitative evaluation was performed by the Cedars-Sinai method. The magnitude of the defect was expressed as a percentage of global myocardial perfusion. RESULTS Total and low density lipoprotein cholesterol levels during placebo were 214 ± 29 mg/dl and 148 ± 25 mg/dl, respectively. These levels with pravastatin were 170 ± 23 mg/dl and 103 ± 23 mg/dl, respectively. The summed stress score and summed rest score were lower with pravastatin than with placebo (7.2 ± 2.3 vs. 5.9 ± 2.3, p = 0.012 and 3.2 ± 1.6 vs. 2.4 ± 2.2, p = 0.043, respectively). Quantitative analysis showed a smaller perfusion defect with pravastatin (29.2%) as compared with placebo (33.8%) (p = 0.021) during dipyridamole stress. No differences were found at rest. CONCLUSIONS Reducing cholesterol levels with pravastatin in patients with CAD improves myocardial perfusion during dipyridamole stress thallium-201 SPECT.

To evaluate low-density lipoprotein-cholesterol (LDLc) goal achievement among dyslipidemic patients treated in lipid and vascular risk units of the Spanish Society of Arteriosclerosis (SEA). The LDLc goal was based on the 2007 European guidelines for cardiovascular prevention.Observational, longitudinal, retrospective, multicenter national study that included consecutive patients of both sexes over 18 years of age referred for dyslipidemia and cardiovascular risk. Information was collected from medical records corresponding to two visits in the lipid unit.We included 1,828 patients from 43 lipid units. In the initial visit, 846 (46.3%) patients were on lipid lowering drug treatment. On the follow-up there was a significant increase in the use of cholesterol-lowering agents, except for a decrease in the use of nicotinic acid. 65.3% of patients with vascular disease and 50.4% with diabetes achieved an LDLc level100mg/dL. Overall, 44.7% of patients achieved the LDLc goal and the predictors in the multivariate analysis were age, waist circumference, diabetes and the presence of vascular disease.Dyslipidemic patients referred to SEA lipid units have improved LDLc goal achievement after follow-up compared with data reported from previous studies in other health care settings. This improvement was associated with a substantial increase in the prescription of statins, both in monotherapy and combined with ezetimibe. There is still a wide room for improvement in the effectiveness of hypercholesterolemia treatment.

Background: Variation in the ankle-brachial index (ABI) is related to the progression of atherosclerosis in the lower extremities and is associated with mid-term cardiovascular morbidity and mortality. The aim of this study was to investigate the changes in ABI after four years of follow-up of individuals in the general population, and the factors associated with relevant variations observed. Patients and methods: The study was performed in 750 volunteers (mean age 69.9 years) men without any evidence of peripheral artery disease, who attended a primary care centre. A complete physical examination, together with standard blood tests and ABI were performed. Four years later a new clinical evaluation was done. Variations in ABI values were considered relevant if > 10 %. Results: Mean ABI in the second visit was 1.07 ± 0.15, which represented 0.02 ± 0.12 points lower than in the first visit (P < 0.001). Of these subjects, 157 (21.6 %) had an ABI decrease > 10 %. Multivariate analysis showed that the change was associated with male gender, cardiovascular history, no intake of blockers of the renin-angiotensin system, and the presence of atherogenic dyslipidaemia. A relevant increase in ABI was observed in 117 subjects (16.1 %), but was not associated with any of the studied factors. Conclusions: ABI values tend to decrease in the general population, although one sixth of the studied subjects had a relevant increase in this parameter.

Patients with peripheral artery disease have a high risk of cardiovascular events and death. The rate of prescription of evidence-based cardiovascular therapies and the attainment of therapeutic goals in this population is suboptimal. There are no previous studies evaluating the rate of prescription of these therapies in our country.PERIFERICA is a cross-sectional study conducted from May to December 2009 in 440 outpatient clinics of general practitioners, internal medicine, cardiology, vascular surgery, endocrinology, and nephrology specialists throughout Spain. Subjects were included if they were aged ≥45 years and had peripheral artery disease and a blood sample obtained during the previous 6 months. Patients were excluded if they had coronary or cerebrovascular diseases. Clinical and anthropometric variables and blood analysis were obtained in all participants.In total, 4087 patients were included in the study (mean age, 68 years; 74% men). There was a high prevalence of diabetes (50%) and hypertension (90%); 79% of participants received lipid-lowering drugs (76% statins), 85.5% antihypertensive drugs (66% renin-angiotensin blockers) and 83% antithrombotics (75% antiplatelet drugs and 11% anticoagulants). In addition, 30% of subjects had a low-density lipoprotein cholesterol concentration n100 mg/dL, 29.5% had optimal control of blood pressure, and 74.5% did not smoke. Only 8% had a good control of all of their cardiovascular risk factors.Although a high percentage of subjects with peripheral artery disease receives adequate treatment with evidence-based preventive therapies, the percentage of subjects with good control of all their risk factors is low.

To estimate the prevalence of peripheral arterial disease as measured on ankle-brachial index and evaluate the associated risk, clinical, and diagnostic factors.Cross-sectional study conducted in a random population-based sample of 2833 individuals aged 25 to 79 years from Don Benito health area (Badajoz). Peripheral arterial disease was considered for ankle-brachial index0.90. To identify symptomatic disease we used the Edinburgh questionnaire. The current screening recommendations, changes to other categories of estimated coronary risk associated with index measurements, and the association with risk factors were assessed.The prevalence of peripheral arterial disease was 3.7% (95% confidence interval, 3.0%-4.5%), 5.0% (3.9%-6.3%) in men and 2.6% (1.8%-3.5%) in women (P=.001). The cumulative prevalence in those aged 50, 60 and 70 years were 6.2%, 9.1%, and 13.1% respectively. The disease was symptomatic in 13.3% (6.8%-19.8%) of cases and 29.6% of asymptomatic patients were not detected as recommended for high-risk groups. The use of ankle-brachial index increased the number of individuals with high coronary risk by 32.7%. Peripheral arterial disease was positively associated with age, smoking, hypercholesterolemia, sedentary lifestyle, microalbuminuria and history of cardiovascular disease, and negatively with alcohol consumption.The use of ankle-brachial index for peripheral arterial disease diagnosis is advisable because of the low prevalence of symptomatic cases and the associated change in estimated coronary risk. Screening groups should be adapted to the Spanish population. Smoking and hypercholesterolemia are major associated risk factors.

The objective of the present study was to compare the acute effect of meals of different composition on the expression of adhesion molecules that play a key role in leucocyte trafficking. A total of twenty apparently healthy subjects randomly consumed three isoenergetic meals 1 week apart: enriched in carbohydrates (CHO), enriched in monounsaturated fat and enriched in saturated fat. Blood samples were obtained before the meals and at 2, 4, 6, 8 and 10 h after meal ingestion. Samples were analysed for LDL resistance to Cu-mediated oxidation and for the surface expression on peripheral blood mononuclear cells (PBMC) of CD62L, CD162, CD11a, CD11b, CD49d and CD54 by flow cytometry. The present results showed that there were no changes in LDL susceptibility to oxidation within and among the meals. After the CHO-enriched meal, there was a time-dependent increased expression of CD162, CD49d, CD11a and CD54 on PBMC that returned to basal values after 8 –10 h. These changes were significantly greater than the ones observed after the consumption of the monounsaturated fat- and the saturated fat-enriched meals and were more evident in lymphocytes than in monocytes. In conclusion, acute ingestion of a CHO-enriched meal induces higher increases of lymphocyte activation markers than fat-enriched meals. These results suggest that long-term consumption of CHO-enriched diets may be associated with a sustained pro-inflammatory state. Monocytes: Lymphocytes: Adhesion molecules: Diet: Carbohydrates: Monounsaturated fat: Saturated fat: Postprandial state

Objective We compared the 1-year predictive value of several inflammatory and non-inflammatory biomarkers in ACS patients. Methods In 610 patients (73.0% male) – 36.0% unstable angina (UA) and 64.0% NSTEMI – we assessed high-sensitivity C-reactive protein (hs-CRP), interleukins 6, 10 and 18, soluble CD40 ligand, P- and E-selectin, NT-proBNP, fibrinogen and cystatin C at hospital admission. Two outcomes at 1-year follow up were selected for analysis: (1) all-cause death, MI, UA, or coronary revascularization, and (2) all-cause death, and non-fatal MI. The effect of biomarker levels on endpoints was examined by the Cox proportional hazards model, and their discrimination ability with the C statistic (AUC). Results Of 549 patients (90.0%) who completed the 1-year follow up, 206 (37.5%) and 54 (8.9%) reached the first and second composite endpoints, respectively. None of the biomarkers studied improved prediction of the first endpoint. However, considered as continuous variables, and in combination, NT-proBNP and fibrinogen, increased the AUC from 0.64 (95% CI 0.55–0.72) to 0.73 (95% CI 0.64–0.81; p =0.02) for prediction of the second endpoint. Cut-off values for NT-proBNP and fibrinogen, regarding best sensitivity and specificity for prediction of the secondary endpoint were 1043.9ng/L and 4.47mg/dL, respectively. For these cut-off points, sensitivity, specificity, positive predictive value and negative predictive value were 40.5% vs 59.5%, 83.3% vs 67.1%, 18.8% vs 14.9% and 93.5% vs 94.4% for NT-proBNP and fibrinogen, respectively. Conclusion In ACS patients, inflammatory biomarkers offer modest incremental information to that provided by clinical risk markers. Fibrinogen and NT-proBNP measurements, however, improve cardiovascular risk prediction.

BACKGROUND To identify factors associated with the discontinuation of evidence-based cardiovascular therapies after hospital discharge for a coronary event. DESIGN Cross-sectional study carried out between June and October 2004 in 1799 primary care centers throughout Spain. PATIENTS AND METHODS Eight thousand eight hundred and seventeen patients (73.7% males; 65.4 years) admitted for coronary disease causes in the past 6 months to 10 years and attending primary care postdischarge from hospital. Current medications, those prescribed at hospital discharge, and the development of adverse events, new risk factors, and comorbidities during follow-up, were collected from clinical records. RESULTS After a median follow-up of 37.4 months, discontinuation rate of lipid-lowering agents, angiotensin renin system blockers, antiplatelet drugs, and beta-blockers were 7.2, 9.1, 10, and 20%, respectively. Of these, 10.8, 16.5, 9.9, and 20.1%, respectively, were because of adverse events. Factors associated with the discontinuation of lipid-lowering agents were the development of hypertension and diabetes during the follow-up. Discontinuation of antiplatelet drug was associated with an earlier history, or with de-novo occurrence, of atrial fibrillation. Discontinuation of angiotensin renin system blockers was associated with the development of atrial fibrillation, diabetes and hypercholesterolemia, and discontinuation of beta-blockers with de-novo appearance of peripheral artery disease, cerebrovascular disease, and heart failure. CONCLUSION In patients followed-up in primary care, the discontinuation rate of cardiovascular disease medications was low and was mainly related to the development of adverse events together with new risk factors and comorbidities arising after hospital discharge.

Patients with polyvascular disease have an increased rate of cardiovascular events and death. Their identification would define a subgroup of the population at very high risk, who would be candidates to intensified preventive measures. The objective of the present study was to evaluate the prevalence of subclinical peripheral artery disease in subjects with a previous diagnosis of vascular disease in other territories.Subjects with a coronary or a cerebrovascular event between 3 months and 5 years, and who were attended at internal medicine outpatient clinics from Spain were included in the study. All patients had a clinical history, a physical examination, a blood and urine analysis, and a measurement of the ankle-brachial index (ABI).A total of 1203 patients (64% males; mean age: 74.3 years), were included in the study. A previous coronary event was reported in 55.4% of the participants, cerebrovascular disease in 38%, and a clinical history of disease in both territories in 6.7%. The prevalence of a low ABI (0,9) was 33.8%, 32.4% and 53.9% for each group, respectively. In a multivariate analysis, factors associated with a low ABI were age, smoking habit, diabetes, a reduced glomerular filtration rate, systolic blood pressure and the presence of clinical disease in both territories upon inclusion. The sensitivity of both, the Edinburgh questionnaire and pulse palpation for detecting and ABI below 0.9, were low.Prevalence of a low ABI is elevated in asymptomatic patients with coronary or cerebrovascular disease, particularly if there are clinical manifestations in both territories.

To evaluate the factors associated with intima-media thickness (IMT) and carotid plaques in patients with familial hypercholesterolemia (FH) and to assess the evolution following 1 year of treatment.Subjects (n=201) diagnosed as having probable or definite FH according to the MED-PED criteria had a clinical history, physical examination, blood chemistry and lipid profile determined. Ultrasound was used to measure the IMT in both common carotid arteries and to assess the presence of plaques. The measurements were repeated in 123 of the patients after 1 year of treatment.Mean age (standard deviation) was 47.8 (13.2) years; 46.3% were males; 11.4% had a clinical history of cardiovascular disease (CVD); 15.9% were hypertensive; 26.4% were smokers; mean plasma total cholesterol concentration was 362 (49)mg/dL; 66.2% had received previous treatment with statins. In the multivariate analysis, baseline IMT was directly associated with age and history of CVD and inversely related to the years of treatment with statins. The presence of carotid plaques was associated directly with the cholesterol-years index and inversely with years of treatment with statins. The mean LDL-cholesterol reduction at 1 year of treatment was 50%. Neither the IMT nor the percentage of patients with plaques changed significantly following 1 year of treatment.Intensive hypocholesterolemic treatment in our patients with probable or definite FH did not increase significantly either the carotid IMT or the prevalence of plaques.

Chronic kidney disease (CKD) increases cardiovascular risk mainly in subjects with coronary heart disease. The aim of this study was to evaluate the prevalence of occult CKD (OCKD) in stable coronary heart disease patients and to study the factors associated in order to improve its detection.Cross sectional study of 7,884 patients who had had a coronary event requiring hospitalization in the previous 6 months to 10 years. Glomerular filtration rate was estimated by means of the Modification of Diet in Renal Disease (MDRD) study equation. CKD was defined as a glomerular filtration rate lower than 60 ml/min/1.73 m(2), and OCKD when, in addition, serum creatinine was133 mmol/l in men and124 mmol/l in women.The mean age was 65.3 years, 73.7% male and 22.4% had CKD, 68.3% of them with normal serum creatinine. In subjects with OCKD the prevalence of risk factors and cardiovascular diseases associated was intermediate between subjects without CKD and subjects with CKD and high serum creatinine. Age, female sex, hypertension, diabetes, heart failure, cerebrovascular disease and peripheral artery disease were significantly and independently associated with OCKD in the multivariate analysis.Almost one in 4 subjects with stable coronary heart disease had CKD, most of them with normal serum creatinine, mainly women and older patients.

ObjectiveSubjects with symptomatic peripheral artery disease (PAD) have an elevated prevalence of carotid stenosis and of silent myocardial ischaemia. As such, clinical guidelines advocate the detection of sub-clinical vascular disease in this population. However, the prevalence of occult vascular disease in asymptomatic patients with a low ankle-brachial index (ABI) has not been previously evaluated.MethodsCross-sectional study in five primary care centres for patients' selection and two University Hospitals for further assessment. Subjects were 1070 asymptomatic individuals between 60 and 80 years of age with at least two cardiovascular risk factors, selected for ankle-brachial index measurement. Eighty five subjects with an ABI 50% and an abnormal EST.ResultsThe prevalence of a low ABI in the overall population was 9.1%. A carotid stenosis >50% was detected in 14.3% of the subjects with a low ABI and in 4.7% of the control subjects (Odds Ratio [OR]: 3.37; 95% Confidence Interval [CI]: 1.04-10.93, P = .033). The prevalence of a positive EST test was 16.2% in those with a low ABI and 10.5% in control subjects (OR: 1.65; 95% CI: 0.63-4.29, P = .309). These prevalences were higher in older subjects, in those with hypertension or diabetes, or in those with dyslipidemia.ConclusionOur results indicate that in high-risk asymptomatic subjects >60 years of age, the presence of an ABI

OBJECTIVE: To evaluate the understanding of patients receiving statins about the dietary and therapeutic measures taken to control their cholesterol and to relate this to the achievement of therapy objectives. DESIGN: Transversal, multi-centre study, conducted between March and November, 2004. SETTING: Three-hundred seventy six primary care and specialist doctors from all over the country. PARTICIPANTS: A total of 2347 patients, with an average age of 59 (12) and 48% women, being treated with statins. METHOD: Survey to evaluate understanding of lipid-lowering diet and pharmacological treatment. The percentage of patients achieving therapy objectives in line with ATP III guidelines was determined. RESULTS: Understanding of diet was adequate only for foods with negative effects on the concentration of cholesterol. Overall, understanding was better in the young, those with a higher level of education, those with hyperlipaemia originating in the family, those under treatment for longer, and in those attended in primary care or internal medicine clinics; it was worse in diabetic patients and in those with cardiovascular disease. Patients with more understanding of their treatment reached their therapy objectives to a greater extent. CONCLUSION: Patients receiving statins treatment have an adequate understanding of diet, but little information on pharmacological treatment. This understanding is associated with the achievement of therapy objectives.

To evaluate whether the presence of chronic kidney disease (CKD) influenced the rate of prescription of evidence-based cardiovascular preventive therapies and attainment of therapeutic goals in patients with stable coronary heart disease, 7,884 patients (mean age 65.4 years; 81.7% men; 22.4% with CKD) attended to in 1,799 primary-care centers and who had had a coronary event requiring hospitalization in the previous 6 months to 10 years were recruited. Glomerular filtration rate (GFR) was estimated using the MDRD Study equation. Results indicated that patients with CKD received more diuretics (47.6% vs 32.8%; p = 0.034), calcium channel blockers (29.3% vs 23.2%, p = 0.027); and blockers of the angiotensin-renin system (76.4% vs 65.3%; p

Atherosclerosis is a widespread, chronic progressive disease that mainly involves medium-sized arteries. Clinically, it can become apparent as ischemic heart disease, cerebrovascular disease, or peripheral arterial disease. In Spain, atherosclerosis is responsible for 124,000 deaths each year. Despite the trend towards a reduction in the aged-adjusted mortality rate for cardiovascular disease, the public health burden is expected to increase. The risk factors are the same for all affected vascular beds, regardless of location, and can be classified as either causal, conditional or predisposing. The presence of atherosclerosis in a particular vascular bed is frequently associated with disease in other vascular territories. Risk assessment tables, inflammatory markers, imaging, and the ankle-brachial index can help in identifying subclinical atherosclerosis. Given the systemic nature of the disease, treatment with statins, antiplatelet agents and angiotensin-converting enzyme inhibitors have consistently proven beneficial, irrespective of the vascular bed affected.

Both decreased GFR and albuminuria are associated with an elevated prevalence of peripheral artery disease. However, the combined effects of these alterations previously were not evaluated. Patients with hypertension and with no known vascular disease (n = 955; mean age 66 yr; 56% male) were selected from internal medicine outpatient clinics throughout Spain. Cardiovascular risk factors, urinary albumin excretion, and the ankle-brachial index (ABI) were assessed in all participants. GFR was estimated according to the Cockroft-Gault equation. Of the study population, 62% had diabetes, 23.8% had a GFR

The Framingham function, recommended by the National Cholesterol Education Program in its document Adult Treatment Panel III (ATP III), and the risk charts of the Systematic Coronary Risk Evaluation (SCORE) program are the most used functions for risk stratification. In both, intensive hygienic and therapeutic measures are recommended for high risk individuals. The objective of the present study was to compare the risk stratification obtained with both functions in a population of subjects older than 60 years.1001 non-diabetic subjects between 60 and 79 years old (mean: 69 years, 67% female) with no evidence of cardiovascular disease were included in the study. Participants were classified as low, moderate or high risk by ATP-III (10%, 10-20% y20% of risk at 10 years, respectively) and by SCORE (3%, 3-4% yor = 5% of risk at 10 years respectively).11.7% of the population was classified as high risk by Framingham and 17.6% by SCORE. Only 5% of the females were classified as high risk with either function. In males, 16.7% and a 44.4% were classified as high risk by Framingham and SCORE respectively. The results did not differ by age group. A 39% of males and a 20% of females were candidates to hypolipidemic treatment as recommended by SCORE guidelines.Compared to Framingham function, the application of SCORE charts to spanish males over 60 years triplicate the number of high risk individuals and candidates to intensive risk factor treatment.

A number of studies have evaluated the effect of the −514C/T polymorphism of the hepatic lipase (HL) gene on concentration and composition of the plasma lipoproteins. However, the effect of this polymorphism on the response to hypolipaemic treatment has not been addressed. We evaluated the effect of this polymorphism on baseline lipids and lipoproteins and their response to treatment comprising 20mg/day pravastatin for 3 months. The study was multi-centred, prospective and interventional in 236 hypercholesterolaemic subjects (mean age 57.3 years; 45% males) from 21 Primary Health-care Centres. The lipid and genotype measurements were conducted centrally. The genotype distribution was 60.2% homozygous for the C allele and 36.0% heterozygous. No significant differences in baseline lipid concentrations between the genotypes were observed, except that carriers of the T allele had higher concentrations of triglycerides ( p =0.021). Post-pravastatin, concentrations of HDL-C increased by 6.9% (95% CI: 2.9–10.8%) in those carrying the T allele with almost no change (0.8%) in the CC genotypes (95% CI: −2.3–4.0%) ( p =0.019). The significance remained ( p =0.014) following adjustment for other confounding factors (age, basal HDL-cholesterol, LDL-cholesterol and triglycerides). We conclude that the −514C/T polymorphism modulates significantly the HDL-C response to pravastatin, irrespective of the baseline lipoprotein concentrations.

C-reactive protein (CRP) is a non-specific but sensitive marker of underlying systemic inflammation. High CRP plasma levels correlate with risk for future cardiovascular events. The present study evaluated the effects of atorvastatin (10-40 mg) and bezafibrate (400 mg) on CRP concentrations after 6 and 12 months of treatment in 103 patients with combined (mixed) hyperlipidemia. The number of cardiovascular risk factors present in a given patient was associated with baseline CRP levels. After 6 months and 1 year, atorvastatin treatment was associated with significant (P

A case of mucormycosis in an AIDS patient is reported. The infection was located in the skin and knee joint after open trauma of the left thigh. Cunninghamella bertholletiae was isolated. The prognosis of this infection is ominous in patients with AIDS because of their precarious immunologic status.