Resilient Older Subjects with Heterozygous Familial Hypercholesterolemia, Baseline Differences and Associated Factors.

Despite elevated low-density lipoprotein (LDL) cholesterol levels, some older subjects with heterozygous familial hypercholesterolemia (HeFH) do not develop atherosclerotic cardiovascular disease (ACVD) during their lifetime. The factors related to this resilient state have not been fully established. The aim of this study was to evaluate differential characteristics between older HeFH subjects with and without ACVD and factors associated with the presence of ACVD. Subjects were part of the Spanish Atherosclerosis Society Dyslipidemia Registry, and those ≥ 70 years old and with HeFH were included. Baseline characteristics of these subjects with and without ACVD were compared. A multivariate analysis was performed to assess factors associated with the presence of ACVD. A total of 2148 subjects with HeFH were included. Resilient subjects were mostly female, younger and presented fewer comorbidities with respect to the ACVD group. Subjects without ACVD had higher baseline high-density lipoprotein (HDL) cholesterol (55.8 ± 17.1 vs. 47.9 ± 15.4 mg/dL; p < 0.001) and lower lipoprotein(a) [Lp(a)] (53.4 ± 67.9 vs. 66.6 ± 85.6 mg/dL; p < 0.001) levels with respect to those in the ACVD group. Lp(a) and the presence of ≥3 risk factors were associated with the presence of ACVD.

Influencia de la concentración de triglicéridos en la lipoproteína(a) en función de la dislipidemia / Influence of triglyceride concentration in lipoprotein (a) as a function of dyslipidemia

Introducción Recientemente se ha demostrado una relación inversa entre la concentración en sangre de la lipoproteína(a) (Lp[a]) y los triglicéridos (TG). A mayor tamaño de lipoproteínas de muy baja densidad (VLDL), mayor presencia de VLDL ricas en apoliproteína E (apo E) y en sujetos con genotipo apo E2/E2, Lp(a) más baja. El mecanismo de esta asociación contrapuesta es desconocido. El objetivo de nuestro análisis fue evaluar la correspondencia Lp(a)-TG en los pacientes atendidos en las Unidades de Lípidos incluidos en el registro de la Sociedad Española de Arteriosclerosis (SEA) comparando las diferentes dislipidemias. Pacientes y métodos Se incluyeron 5.275 usuarios de ≥ 18 años registrados antes del 31 de marzo de 2023, con datos de concentración de Lp(a) e información completa del perfil lipídico sin tratamiento. Resultados La media de edad fue de 53,0 ± 14,0 años, con 48% de mujeres. Un total de 9,5% (n = 502) tenían diabetes mellitus (DM) y 1.184 sujetos (22,4%) presentaban obesidad. La mediana de TG fue de 130 mg/dL (rango intercuartílico [IQR] 88,0-210) y de Lp(a) 55,0 nmol/L (IQR 17,9 -156). La concentración de Lp(a) mostró una asociación negativa con la de TG cuando los valores de estos superaban los 300 mg/dL. Los pacientes con TG > 1.000 mg/dL mostraron el menor nivel de Lp(a) 17,9 nmol/L y los usuarios con TG < 300 mg/dL, presentaron una media de Lp(a) de 60,1 nmol/L. En pacientes sin DM ni obesidad, la relación inversa de Lp(a)-TG fue especialmente importante (p < 0,001). La mediana de Lp(a) fue de 58,3 nmol/L en aquellos con TG < 300 mg/dL y 22,0 nmol/L si TG > 1.000 mg/dL. No se encontró asociación entre TG y Lp(a) en sujetos con DM y obesidad, ni en los que contaban con hipercolesterolemia familiar (HF). En los que padecen hiperlipemia combinada multifactorial con TG < 300 mg/dL la Lp(a) fue 64,6 nmol/L, en el rango de 300-399 mg/dL de TG la Lp(a) desciende hasta 38,8 nmol/L y hasta 22,3 nmol/L si TG > 1.000 mg/dL. Conclusiones ... (AU)

Background Recently, an inverse relationship between the blood concentration of lipoprotein(a) (Lp(a)) and triglycerides (TG) has been demonstrated. The larger the VLDL particle size, the greater the presence of VLDL rich in apoliprotein E and in subjects with the apoE2/E2 genotype, the lower Lp(a) concentration. The mechanism of this inverse association is unknown. The objective of this analysis was to evaluate the Lp(a)–TG association in patients treated at the lipid units included in the registry of the Spanish Society of Atherosclerosis (SEA) by comparing the different dyslipidemias. Patients and methods Five thousand two hundred and seventy-five subjects ≥18 years of age registered in the registry before March 31, 2023, with Lp(a) concentration data and complete lipid profile information without treatment were included. Results The mean age was 53.0 ± 14.0 years, with 48% women. The 9.5% of subjects (n = 502) had diabetes and the 22.4% (n = 1184) were obese. The median TG level was 130 mg/dL (IQR 88.0–210) and Lp(a) 55.0 nmol/L (IQR 17.9–156). Lp(a) concentration showed a negative association with TG concentration when TG values exceeded 300 mg/dL. Subjects with TG > 1000 mg/dL showed the lowest level of Lp(a), 17.9 nmol/L, and subjects with TG < 300 mg/dL had a mean Lp(a) concentration of 60.1 nmol/L. In subjects without diabetes or obesity, the inverse association of Lp(a)–TG was especially important (p < 0.001). The median Lp(a) was 58.3 nmol/L in those with TG < 300 mg/dL and 22.0 nmol/L if TG > 1000 mg/dL. No association was found between TG and Lp(a) in subjects with diabetes and obesity, nor in subjects with familial hypercholesterolemia. In subjects with multifactorial combined hyperlipemia with TG < 300 mg/dL, Lp(a) was 64.6 nmol/L; in the range of 300–399 mg/dL of TG, Lp(a) decreased to 38. 8 nmol/L, and up to 22.3 nmol/L when TG > 1000 mg/dL. Conclusions ... (AU)

Factors associated with the presence of tendon xanthomas in familial hypercholesterolemia.

INTRODUCTION AND OBJECTIVES: Tendon xanthomas (TX) are lipid deposits highly specific to familial hypercholesterolemia (FH). However, there is significant variability in their presentation among FH patients, primarily due to largely unknown causes. Lipoprotein(a) is a well-established independent risk factor for atherosclerotic cardiovascular disease in the general population as well as in FH. Given the wide variability of lipoprotein(a) among FH individuals and the likelihood that TX may result from a proatherogenic and proinflammatory condition, the objective of this study was to analyze the size of TX in the Achilles tendons of FH participants and the variables associated with their presence, including lipoprotein(a) concentration. METHODS: A cross-sectional study was conducted on 377 participants with a molecular diagnosis of heterozygous FH. Achilles tendon maximum thickness (ATMT) was measured using ultrasonography with standardized equipment and procedures. Demographic variables and lipid profiles were collected. A multivariate linear regression model using a log-Gaussian approach was used to predict TX size. Classical cardiovascular risk factors and lipoprotein(a) were included as explanatory variables. RESULTS: The mean low-density lipoprotein cholesterol level was 277mg/dL without lipid-lowering treatment, and the median ATMT was 5.50mm. We demonstrated that age, sex, low-density lipoprotein cholesterol, and lipoprotein(a) were independently associated with ATMT. However, these 4 variables did not account for most the interindividual variability observed (R2=0.205). CONCLUSIONS: TX, a characteristic hallmark of FH, exhibit heterogeneity in their presentation. Interindividual variability can partially be explained by age, male sex, low-density lipoprotein cholesterol, and lipoprotein(a) but these factors account for only 20% of this heterogeneity.

Influence of triglyceride concentration in lipoprotein (a) as a function of dyslipidemia. / Influencia de la concentración de triglicéridos en la lipoproteína(a) en función de la dislipidemia.

BACKGROUND: Recently, an inverse relationship between the blood concentration of lipoprotein(a) (Lp(a)) and triglycerides (TG) has been demonstrated. The larger the VLDL particle size, the greater the presence of VLDL rich in apoliprotein E and in subjects with the apoE2/E2 genotype, the lower Lp(a) concentration. The mechanism of this inverse association is unknown. The objective of this analysis was to evaluate the Lp(a)-TG association in patients treated at the lipid units included in the registry of the Spanish Society of Atherosclerosis (SEA) by comparing the different dyslipidemias. PATIENTS AND METHODS: Five thousand two hundred and seventy-five subjects ≥18 years of age registered in the registry before March 31, 2023, with Lp(a) concentration data and complete lipid profile information without treatment were included. RESULTS: The mean age was 53.0 ± 14.0 years, with 48% women. The 9.5% of subjects (n = 502) had diabetes and the 22.4% (n = 1184) were obese. The median TG level was 130 mg/dL (IQR 88.0-210) and Lp(a) 55.0 nmol/L (IQR 17.9-156). Lp(a) concentration showed a negative association with TG concentration when TG values exceeded 300 mg/dL. Subjects with TG > 1000 mg/dL showed the lowest level of Lp(a), 17.9 nmol/L, and subjects with TG < 300 mg/dL had a mean Lp(a) concentration of 60.1 nmol/L. In subjects without diabetes or obesity, the inverse association of Lp(a)-TG was especially important (p < 0.001). The median Lp(a) was 58.3 nmol/L in those with TG < 300 mg/dL and 22.0 nmol/L if TG > 1000 mg/dL. No association was found between TG and Lp(a) in subjects with diabetes and obesity, nor in subjects with familial hypercholesterolemia. In subjects with multifactorial combined hyperlipemia with TG < 300 mg/dL, Lp(a) was 64.6 nmol/L; in the range of 300-399 mg/dL of TG, Lp(a) decreased to 38. 8 nmol/L, and up to 22.3 nmol/L when TG > 1000 mg/dL. CONCLUSIONS: Our results show an inverse Lp(a)-TG relationship in TG concentrations > 300 mg/dL in subjects without diabetes, obesity and without familial hypercholesterolemia. Our results suggest that, in those hypertriglyceridemias due to hepatic overproduction of VLDL, the formation of Lp(a) is reduced, unlike those in which the peripheral catabolism of TG-rich lipoproteins is reduced.

Low-Quality Carbohydrate Intake Is Associated With a Higher Prevalence of Metabolic Syndrome: The AWHS Study.

CONTEXT: The relationship between carbohydrate quality intake and metabolic syndrome (MetS) is of growing interest. OBJECTIVE: We aimed to assess the association between the adherence to a dietary carbohydrate quality index (CQI) with the occurrence of MetS in a Spanish cohort of working adults. METHODS: A cross-sectional study was conducted of 2316 middle-aged men, aged 50.9 (SD 3.9) years, with no previous cardiovascular disease, and pertaining to the Aragon Workers' Health Study (AWHS) cohort. Diet was collected with a 136-item semiquantitative food-frequency questionnaire. The CQI (range 4-15) was based on: dietary fiber intake, a low glycemic index, the ratio of whole grains/total grains, and the ratio of solid carbohydrates/total carbohydrates. The higher the CQI, the healthier the diet. MetS was defined by using the harmonized National Cholesterol Education Programme-Adult Treatment Panel III (NCEP-ATP III) definition. The associations across 3-point categories of the CQI and the presence of MetS were examined using logistic regression. RESULTS: An inverse and significant association between the CQI and MetS was found. Fully adjusted odds ratios (ORs) for MetS risk among participants in the 10- to 12-point category (second highest CQI category) was 0.64 (95% CI, 0.45-0.94), and in the 13- to 15-point category (highest category) was 0.52 (95% CI, 0.30-0.88), when compared with the 4- to 6-point category (lowest category). Participants with 10 to 12 and 13 to 15 points on the CQI showed a lower risk of hypertriglyceridemia: OR 0.61 (95% CI, 0.46-0.81), and 0.48 (95% CI, 0.32-0.71) respectively. CONCLUSION: Among middle-aged men, a higher adherence to a high-quality carbohydrate diet is associated with a lower prevalence of MetS. Triglyceridemia is the MetS component that contributed the most to this reduced risk.

Estrategias de tratamiento de las dislipemias en prevención primaria y secundaria. Registro de la Sociedad Española de Arteriosclerosis / Dyslipidemia treatment strategies in primary and secondary prevention. Dyslipemia Registry of the Spanish Arteriosclerosis Society

Introducción: Los estudios clínicos reflejan que los pacientes con riesgo cardiovascular elevado todavía están lejos de alcanzar los objetivos terapéuticos, especialmente de los niveles de cLDL. Si el manejo de estos pacientes en unidades especializadas difiere de otros escenarios no es conocido. Pacientes y métodos: Se seleccionaron 61 Unidades de Lípidos certificadas en el Registro de Dislipemias de la Sociedad Española de Arteriosclerosis para la recogida de datos del estudio. Se incluyeron 3.58 sujetos > 18 años que cumplían los criterios de hipercolesterolemia (colesterol LDL ≥ 160 mg/dL o colesterol no HDL ≥ 190 mg/dL) sin hipercolesterolemia familiar. Un total de 1.665 sujetos fueron estudiados con un tiempo medio de seguimiento de 4,2 años. Resultados y conclusiones: Un total de 42 sujetos tuvieron un evento cardiovascular desde su inclusión en el Registro, que supone 0,6%. No hubo diferencias en el tratamiento utilizado al inicio del seguimiento entre los sujetos con y sin evento prospectivo. El cLDL mejoró durante el seguimiento, pero 50% de los pacientes no alcanzaron los objetivos terapéuticos en la visita final del seguimiento. Se observó un aumento del uso de tratamiento hipolipemiante de alta potencia, incluyendo los inhibidores de PCSK9 en un 16,7% de los sujetos con recurrencias.(AU)

Introduction: Clinical studies show that patients with high cardiovascular risk are still far from reaching the therapeutic objectives, especially of the levels of LDL cholesterol. If the management of these patients in specialized units differs from other scenarios is known. Patients and methods: 61 certified Lipid Units were selected in the Registry of Dyslipemias of the Spanish Arteriosclerosis Society for the collection of study data. The study included 3958 subjects >18 years of age who met the criteria for hypercholesterolemia (LDL cholesterol ≥160 mg/dL or non-HDL cholesterol ≥190 mg/dL) without familial hypercholesterolemia. A total 1,665 subjects were studied with a mean follow-up time of 4.2 years. Results and conclusions: A total of 42 subjects had a cardiovascular event since their inclusion in the Registry, which represents 0.6%. There were no differences in the treatment used at follow-up, but 50% of the patients did not reach the therapeutic goals at the visit end of follow-up. An increase in the potency of the lipid-lowering treatment was observed, including PCSK9 inhibitors use in 16.7% of subjects with recurrences.(AU)

Papel de los lípidos en la ateroesclerosis / The role of lipids in atherosclerosis

En los últimos años se ha demostrado que la concentración en sangre de las partículas que contienen Ateroesclerosis apolipoproteína B, muy especialmente las lipoproteínas de baja densidad (LDL) y la lipoproteîna(a) [Lp(a)], no es un factor de riesgo asociado con la enfermedad cardiovascular, sino un factor etiológico de primera magnitud. Los estudios observacionales prospectivos, los estudios de aleatorización mendeliana, los modelos animales de arterioesclerosis manipulando genes relacionados con los lípidos, enfermedades genéticas humanas, como la hipercolesterolemia familiar monogénica o las altas concentraciones de Lp(a), y los estudios de intervención con hipolipemiantes nos han dado una incuestionable evidencia al respecto. En el presente artículo se repasa está evidencia, así como los principales mecanismos patogénicos que hacen del colesterol unido a LDL (cLDL) una de las principales causas de la enfermedad cardiovascular ateromatosa

In recent years, it has been shown that the circulating level of particles containing apolipoprotein B, especially low-density lipoproteins (LDLs) and lipoprotein(a), is not a risk factor for cardiovascular disease but is instead a major etiological factor. Indisputable evidence has come from prospective observational studies, Mendelian randomization studies, animal models of arteriosclerosis involving the manipulation of lipid-related genes, human genetic diseases (e.g. monogenic familial hypercholesterolemia and hypercholesterolemia associated with an elevated lipoprotein(a) concentration), and interventional studies with lipid-lowering agents. This article reviews these findings and summarizes current understanding of the principle pathogenic mechanisms that make LDL cholesterol one of the main causes of atherosclerotic cardiovascular disease

Tratamiento de un varón con enfermedad de McArdle y muy alto riesgo cardiovascular con inhibidores de PCSK9 / Treatment of a high cardiovascular risk patient with McArdle's disease with PCSK9 inhibitors

Varón de 60 años con hiperlipidemia familiar combinada, cardiopatía isquémica y diabetes tipo 2. Desde la infancia, intolerancia al esfuerzo intenso. Se le diagnosticó enfermedad de McArdle a raíz de rabdomiólisis asociada a estatinas tras un infarto de miocardio. Desde entonces había seguido tratamiento con dieta, fibratos y ezetimiba con buena tolerancia, pero a pesar de ello las concentraciones de colesterol LDL (cLDL) eran > 180 mg/dl. Se asoció al tratamiento alirocumab 150 mg subcutáneos cada 14 días, con excelente respuesta clínica y descenso de cLDL a 15 mg/dl, manteniéndose estable desde entonces. Nuestro caso demuestra que los inhibidores de PCSK9 son eficaces y seguros en pacientes con enfermedades musculares que contraindican las estatinas y que son una alternativa terapéutica ideal para este tipo de pacientes

A 60-year-old male with familial combined hyperlipidemia, ischemic heart disease and type 2 diabetes. Since childhood, intolerance to intense exercise. The patient was diagnosed of McArdle's disease after an episode of rhabdomyolysis associated with statins as treatment after a myocardial infarction. Since then, he had been treated with diet, fibrates and ezetimibe with good tolerance, despite this, LDL cholesterol (cLDL) remained > 180 mg/dl. He started to be treated with alirocumab 150mg/sc every 14 days, with excellent clinical response and a decrease in cLDL to 15 mg/dl. Our case shows that PCSK9 inhibitors are effective and safe in patients with muscle diseases who have statin contraindication, and they are a good therapeutic tool for these patients

Variantes de un solo nucleótido asociadas con la hipercolesterolemia poligénica en familias diagnosticadas de hipercolesterolemia familiar / Single nucleotide variants associated with polygenic hypercholesterolemia in families diagnosed clinically with familial hypercholesterolemia

Introducción y objetivos: Aproximadamente un 20-40% de los casos de hipercolesterolemia familiar diagnosticada no muestran mutación causal en los genes candidatos, por lo que algunos de estos casos pueden tener un origen poligénico. Se han identificado diferentes variantes genéticas de un solo nucleótido que ayudan a diferenciar las hipercolesterolemias poligénicas de las monogénicas. El objetivo es estudiar la contribución de dichas variantes a la concentración de colesterol unido a lipoproteínas de baja densidad (cLDL) en probandos con hipercolesterolemia genética sin mutación en genes candidatos (hipercolesterolemia genética sin hipercolesterolemia familiar) y establecer el valor de una puntuación genética basada en las frecuencias de dichas variantes de un solo nucleótido en el cribado en cascada de sus familiares. Métodos: Se reclutó a 49 familias con hipercolesterolemia genética sin hipercolesterolemia familiar (294 sujetos) y se calculó la puntuación genética derivada de las variantes de un solo nucleótido de los genes SORT1, APOB, ABCG8, APOE y LDLR más la concentración plasmática de lipoproteína(a). Resultados: Los alelos de riesgo en SORT1, ABCG8, APOE y LDLR presentaron mayor frecuencia en los consanguíneos que en el proyecto 1.000 Genomas, con diferencia estadísticamente significativa. La contribución de la puntuación genética a la concentración plasmática de cLDL fue significativamente mayor en los sujetos afectados de hipercolesterolemia que en los de control (p = 0,048). El porcentaje de la variación de cLDL explicado por la puntuación fue del 3,1%, que aumentó al 6,9% seleccionando a las familias con puntuación genética más alta en el probando. Conclusiones: Las familias con hipercolesterolemia genética sin hipercolesterolemia familiar concentran los alelos de riesgo de cLDL alto. Su contribución varía mucho entre las familias, lo que indica la complejidad y la heterogeneidad de estas formas de hipercolesterolemia. La puntuación genética explica un pequeño porcentaje del cLDL, lo que limita su uso diagnóstico

Introduction and objectives: Approximately 20% to 40% of clinically defined familial hypercholesterolemia cases do not show a causative mutation in candidate genes, and some of them may have a polygenic origin. A cholesterol gene risk score for the diagnosis of polygenic hypercholesterolemia has been demonstrated to be valuable to differentiate polygenic and monogenic hypercholesterolemia. The aim of this study was to determine the contribution to low-density lipoprotein cholesterol (LDL-C) of the single nucleotide variants associated with polygenic hypercholesterolemia in probands with genetic hypercholesterolemia without mutations in candidate genes (nonfamilial hypercholesterolemia genetic hypercholesterolemia) and the genetic score in cascade screening in their family members. Methods: We recruited 49 nonfamilial hypercholesterolemia genetic hypercholesterolemia families (294 participants) and calculated cholesterol gene scores, derived from single nucleotide variants in SORT1, APOB, ABCG8, APOE and LDLR and lipoprotein(a) plasma concentration. Results: Risk alleles in SORT1, ABCG8, APOE, and LDLR showed a statistically significantly higher frequency in blood relatives than in the 1000 Genomes Project. However, there were no differences between affected and nonaffected members. The contribution of the cholesterol gene score to LDL-C was significantly higher in affected than in nonaffected participants (P = .048). The percentage of the LDL-C variation explained by the score was 3.1%, and this percentage increased to 6.9% in those families with the highest genetic score in the proband. Conclusions: Nonfamilial hypercholesterolemia genetic hypercholesterolemia families concentrate risk alleles for high LDL-C. Their contribution varies greatly among families, indicating the complexity and heterogeneity of these forms of hypercholesterolemias. The gene score explains a small percentage of LDL-C, which limits its use in diagnosis

Asociación de la presencia de placa carotídea en la aparición de eventos cardiovasculares en pacientes con hipercolesterolemias genéticas / Association between the presence of carotid artery plaque and cardiovascular events in patients with genetic hypercholesterolemia

Introducción y objetivos: Las ecuaciones de riesgo empleadas en población general no son de utilidad en hipercolesterolemias genéticas (HG). Las placas carotídeas se han demostrado útiles en la predicción cardiovascular y la reclasificación del riesgo. Su utilidad en HG no se ha estudiado y es el objetivo del estudio. Métodos: Se incluyó a 1.778 sujetos con HG y una media de seguimiento de 6,26 años hasta la aparición de eventos cardiovasculares, en los que al inicio se estudió la presencia de placas en carótidas por ecografía de alta resolución. Resultados: Se encontraron placas en 661 (37,2%) sujetos: el 31,9% con hipercolesterolemia familiar, el 39,8% en hiperlipemia familiar combinada, el 45,5% en disbetalipoproteinemia y el 43,2% en hipercolesterolemia poligénica. Durante el seguimiento, 58 pacientes sufrieron un evento cardiovascular. La tasa de eventos fue 6.354/100.000 (IC95%, 4.432,4-8.275,6) en el grupo con placa y 1.432/100.000 (IC95%, 730,6-2.134,3) en el grupo sin placa, con diferencia significativa entre ambos grupos (p < 0,001). El riesgo de sufrir un evento de los sujetos con placa fue 4,34 (IC95%, 2,44-7,71; p < 0,001) veces superior en presencia de placa y 2,40 (IC95%, 1,27-4,56; p = 0,007) veces superior tras ajustar por los principales factores de riesgo. El número total de placas se asoció positivamente con el riesgo de eventos. Conclusiones: La detección de placas carotídeas identifica a un subgrupo de pacientes que concentran la mayoría de los eventos cardiovasculares. Estos resultados respaldan la utilización de la detección de placas en esta población y deben ayudar en la estratificación del riesgo y la planificación del tratamiento en las HG (AU)

Introduction and objectives: The equations used in the general population to calculate cardiovascular risk are not useful in genetic hypercholesterolemia (GH). Carotid plaque detection has proved useful in cardiovascular prediction and risk reclassification but there have been no studies of its usefulness in GH. The aim of this study was to determine the association between the presence of carotid artery plaque and the occurrence of cardiovascular events in patients with GH. Methods: This study included 1778 persons with GH. The mean follow-up until the occurrence of cardiovascular events was 6.26 years. At presentation, the presence of carotid artery plaque was studied by high-resolution ultrasound. Results: Carotid artery plaque was found in 661 (37.2%) patients: 31.9% with familial hypercholesterolemia, 39.8% with familial combined hyperlipidemia, 45.5% with dysbetalipoproteinemia, and 43.2% with polygenic hypercholesterolemia. During follow-up, 58 patients had a cardiovascular event. Event rates were 6354/100 000 (95%CI, 4432.4-8275.6) in the group with plaque and 1432/100 000 (95%CI, 730.6-2134.3) in the group without plaque, with significant differences between the 2 groups (P < .001). The relative risk of an event was 4.34 (95CI%, 2.44-7.71; P < .001) times higher in patients with plaque and was 2.40 (95%CI, 1.27-4.56; P = .007) times higher after adjustment for major risk factors. The number of carotid artery plaques was positively associated with the risk of cardiovascular events. Conclusions: Most cardiovascular events occur in a subgroup of patients who can be identified by carotid plaque detection. These results support the use of plaque screening in this population and should help in risk stratification and treatment in GH (AU)