José M. Mostaza

La aplicación de las tablas del SCORE a varones de edad avanzada triplica el número de sujetos clasificados de alto riesgo en comparación con la función de Framingham

Fundamento y objetivo La funcion de Framingham, recomendada por el National Cholesterol Education Program en su documento Adult Treatment Panel III (ATP-III) y las tablas de riesgo del Systematic Coronary Risk Evaluation (SCORE) son las funciones mas utilizadas para la estratificacion del riesgo cardiovascular, y ambas recomiendan intensificar las medidas higienicas y terapeuticas en las personas que presenten un riesgo alto. El objetivo del presente estudio fue comparar la estratificacion del riesgo obtenida con ambas clasificaciones en una poblacion de sujetos mayores de 60 anos. Sujetos y metodo Se incluyo en el estudio a 1.001 personas no diabeticas de entre de 60 y 79 anos (media de 69 anos, un 67%, mujeres) sin evidencia de enfermedad vascular. Se clasifico a los participantes segun su riesgo fuera bajo, medio o alto de acuerdo con el ATP-III ( 20% de riesgo a los 10 anos, respectivamente) y el SCORE ( Resultados Un 11,7% de la poblacion se considero de riesgo alto segun la ecuacion de Framingham, frente a un 17,6% segun el SCORE. Unicamente un 5% de las mujeres fueron clasificadas de riesgo alto con cualquiera de las funciones, frente a un 16,7 y un 44,4% de los varones segun las tablas de Framingham y de SCORE, respectivamente. Los resultados fueron similares al dividir por grupos de edad. De acuerdo con las guias del SCORE, un 39% de los varones y un 20% de las mujeres eran candidatos a recibir tratamiento hipolipemiante. Conclusiones En comparacion con la funcion de Framingham, la aplicacion del SCORE en varones mayores de 60 anos triplica el numero de sujetos de alto riesgo candidatos a medidas de prevencion energicas.

Cholesterol reduction improves myocardial perfusion abnormalities in patients with coronary artery disease and average cholesterol levels

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.

Effect of apoE genotype on the hypolipidaemic response to pravastatin in an outpatient setting

Abstract. Peña R, Lahoz C, Mostaza JM, Jiménez J, Subirats E, Pintó X, Taboada M, López‐Pastor A, The RAP study group (Hospital Carlos III; Instituto de Salud Carlos III, Madrid; Hospital de Puigcerdá, Gerona; Hospital de Bellvitge, Barcelona; Centro de Salud de Fuencarral; Hospital La Paz, Madrid, Spain). Effect of apoE genotype on the hypolipidaemic response to pravastatin in an outpatient setting. J Intern Med 2002; 251: 518–525.

Effect of atorvastatin and bezafibrate on plasma levels of C-reactive protein in combined (mixed) hyperlipidemia

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<0.001) decreases from baseline of CRP concentrations by 29 and 43%, respectively, while bezafibrate-treated patients showed non-significant reductions of 2.3 and 14.6%, respectively (P=0.056 and 0.005 for the respective differences between the two treatment arms at 6 months and 1 year). The magnitude of change in CRP after 1 year was directly related to baseline CRP levels. Covariance analysis showed that CRP decreases in the atorvastatin group were unrelated to total cholesterol and LDL cholesterol reductions; however, they were directly related to triglyceride changes (r=0.28, P=0.047) and inversely related to HDL cholesterol changes (r=-0.28, P=0.045). A model including baseline CRP values and treatment effect showed that atorvastatin use was a significant predictor of change in CRP levels over time (beta=0.82, P=0.023). These results suggest a potential anti-atherosclerotic additional benefit of atorvastatin in patients at a risk of cardiovascular disease.

La aterosclerosis como enfermedad sistémica

La aterosclerosis es una enfermedad cronica, generalizada y progresiva que afecta sobre todo a las arterias de mediano tamano. Clinicamente se manifiesta como cardiopatia isquemica, enfermedad cerebrovascular o enfermedad arterial periferica (EAP). En nuestro pais es la causa de 124.000 muertes anuales. A pesar de la tendencia a la disminucion de la tasa ajustada por edad de la mortalidad por las enfermedades cardiovasculares, el impacto sanitario de estas se espera que aumente. Los factores de riesgo son los mismos para los distintos territories vasculares y se pueden clasificar como causales, condicionales o predisponentes. La presencia de aterosclerosis en un territorio vascular se asocia con frecuencia con la afectacion de otros territorios. Las tablas para la estimacion del riesgo, los marcadores de inflamacion, las pruebas de imagen y el indice tobillo-brazo pueden ser utiles para detectar la presencia de aterosclerosis subclinica. Dado que es una enfermedad sistemica, el tratamiento con estatinas, antiagregantes plaquetarios o inhibidores de la enzima de conversion de la angiotensina han demostrado consistentemente su beneficio, con independencia del lecho vascular afectado.

Elevated serum neopterin levels and adverse cardiac events at 6 months follow-up in Mediterranean patients with non-ST-segment elevation acute coronary syndrome

BACKGROUND Little information exists regarding the prognostic role of biomarkers of inflammation in Mediterranean patients. High C-reactive protein and neopterin levels - a marker of macrophage activation - predict cardiovascular events in stable angina patients and patients with acute coronary syndromes (ACS). We sought to assess whether plasma neopterin levels predict adverse clinical outcomes in Mediterranean patients with non-ST elevation (NSTE) ACS, i.e. unstable angina (UA) and NSTE myocardial infarction (MI). METHODS We prospectively assessed 397 patients (74% men) admitted with NSTEACS, 147 (37%) had unstable angina and 250 (63%) NSTEMI. Blood samples for neopterin and CRP assessment were obtained at admission. The study endpoint was the composite of cardiac death, acute myocardial infarction and unstable angina at 180 days. RESULTS Baseline neopterin concentrations (nmol/L) were similar in unstable angina and NSTEMI patients (8.3 [6.6-10.7] vs. 7.9 [6.2-10.9]; p=0.4). Fifty-nine patients (14.9%) had events during follow-up. Twenty-nine (21.5%) patients with neopterin levels in the highest third experienced the combined endpoint, compared to 30 (11.5%) patients with neopterin levels in the second and the lowest thirds (log-rank 7.435, p=0.024). On multivariable hazard Cox regression, neopterin (highest vs. 1st and 2nd thirds, HR 1.762, 95% CI [1.023-3.036]) was independently associated with the combined endpoint. CONCLUSION Increased neopterin levels are an independent predictor of 180-day adverse cardiac events in Mediterranean patients with NSTEACS.

A comparative study of biomarkers for risk prediction in acute coronary syndrome—Results of the SIESTA (Systemic Inflammation Evaluation in non-ST-elevation Acute coronary syndrome) study

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 1043.9 ng/L and 4.47 mg/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.

Apo A-I promoter polymorphism influences basal HDL-cholesterol and its response to pravastatin therapy

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.

Atherosclerosis As a Systemic Disease

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.

Relationship between Ankle-Brachial Index and Chronic Kidney Disease in Hypertensive Patients with No Known Cardiovascular Disease

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 <60 ml/min per 1.73 m2, and 43.8% had albuminuria. The prevalence of ABI <0.9 was greater in patients with a GFR <60 ml/min per 1.73 m2 (37.4 versus 24.3%; P < 0.0001) and in those who had albuminuria (32.2 versus 23.3%; P = 0.001). In patients with both alterations, the prevalence of ABI <0.9 was 45.7%. Multivariate analysis indicated that the factors that were associated independently with low ABI were age (odds ratio [OR] 1.06; 95% confidence interval [CI] 1.03 to 1.08; P < 0.0001), triglyceride concentration (OR 1.003; 95% CI 1.001 to 1.005; P = 0.001), presence of albuminuria (OR 1.61; 95% CI 1.18 to 2.20; P = 0.003), smoking habit (OR 1.72; 95% CI 1.13 to 2.63; P = 0.012), and a GFR <60 ml/min per 1.73 m2 (OR 1.47; 95% CI 1.01 to 2.17; P = 0.049). In patients with hypertension and without known vascular disease, reduced GFR and albuminuria are associated independently with an ABI <0.9. Their combined presence characterizes a subgroup of the population who have an elevated prevalence of peripheral artery disease and could benefit from early diagnosis and treatment.