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.

Prescribing statin therapy in physically (in)active individuals vs prescribing physical activity in statin-treated patients: A four-scenario practical approach.

Statins are among the most commonly prescribed medications worldwide. Statin-associated muscle symptoms (SAMS) represent a frequent statin-related adverse effect associated with statin discontinuation and increased cardiovascular disease (CVD) events. Emerging evidence indicate that the majority of SAMS might not be actually caused by statins, and the nocebo/drucebo effect (i.e. adverse effects caused by negative expectations) might also explain SAMS. Physical activity (PA) is a cornerstone in the management of CVD risk. However, evidence of increased creatine-kinase levels in statin-treated athletes exposed to a marathon has been generalized, at least to some extent, to the general population and other types of PA. This generalization is likely inappropriate and might induce fear around PA in statin users. In addition, the guidelines for lipid management focus on aerobic PA while the potential of reducing sedentary behavior and undertaking resistance training have been overlooked. The aim of this report is to provide a novel proposal for the concurrent prescription of statin therapy and PA addressing the most common and clinically relevant scenarios by simultaneously considering the different stages of statin therapy and the history of PA. These scenarios include i) statin therapy initiation in physically inactive patients, ii) PA/exercise initiation in statin-treated patients, iii) statin therapy initiation in physically active patients, and iv) statin therapy in athletes and very active individuals performing SAMS-risky activities.

Association between non-dipper hypertension and vitamin D deficiency in women with systemic lupus erythematosus.

OBJECTIVES: Blood pressure (BP) physiologically declines more than 10% at night. Subjects who do not experience this drop are classified as non-dippers. They have a higher risk of cardiovascular diseases (CVD). Vitamin D deficiency and non-dipper pattern have been associated in the general population. Patients with systemic lupus erythematosus (SLE) are more likely to have vitamin D deficiency, a non-dipper pattern and CVD. We aimed to evaluate a possible relationship between vitamin D deficiency and non-dipper pattern in patients with SLE. METHODS: Using 24-hour ambulatory BP monitoring, 77 women with SLE were divided into dippers and non-dippers. 25-hydroxyvitamin D (25(OH)D) levels were compared between both groups. A multivariate analysis was used to determine which variables were independently associated with non-dipper pattern. RESULTS: 62% of patients were non-dippers. They had lower levels of 25(OH)D than dippers (19.4±8.9 vs. 25.9±10.1 ng/ml, p=0.005). Patients with lower 25(OH)D levels were more likely to be non-dippers (OR 3.7, 95%CI 1.2-11.4; p=0.025). The nocturnal decline of mean BP correlated with levels of 25(OH)D (r=0.227, p=0.047). Night-time systolic, diastolic and mean BP inversely correlated with the levels of 25(OH)D (r=-0.274, p=0.016; r=-0.238, p=0.037, and r=-0.260, p=0.022, respectively), but only night- time systolic BP remained significant after adjustment for age and body mass index (r=-0.228, p=0.049). 25(OH)D levels and the use of mycophenolate were found to be independently associated with non-dipper pattern in SLE patients. CONCLUSIONS: Vitamin D deficiency may contribute to the development of a non-dipper pattern in patients with SLE.

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.

Concentration of low-density lipoproteins (LDL) is significantly reduced after nilotinib discontinuation.

Dyslipidemia is a frequent side effect associated with nilotinib treatment. Patients with chronic myeloid leukemia (CML) under treatment with nilotinib who develop dyslipidemia have been shown to have a higher risk of presenting atherosclerotic cardiovascular disease (ACVD). Therapeutic discontinuation in selected individuals could be a strategy in order to prevent the development of ACVD. Observational study of patients with CML under nilotinib treatment. The lipid values were gathered before starting with nilotinib and after 3 months. Such values were also measured before discontinuation in patients who suspended nilotinib treatment, as well as 3 and 12 months later. 32 patients were included, 19 of them treated in monotherapy with nilotinib. The concentrations of total cholesterol and low-density lipoproteins (LDL) increased significantly after 3 months of treatment (27.29 mg/dL ± 22.88, p < 0.01). Of the total number of patients treated, 12 discontinued the treatment. LDL concentration was significantly reduced after 3 months of the nilotinib discontinuation (- 27.58 mg/dL ± 38.30, p = 0.030), remaining substantially lower after 12 months, compared to the time previous to discontinuation (- 24.58 mg/dL ± 37.31, p = 0.043). Nilotinib suspension reduces significantly LDL concentrations. These data support the strategy of therapeutic discontinuation in order to prevent future cardiovascular complications, especially in patients with prior cardiovascular risk factors.

Arterial hypertension assessment in a population with chronic myeloid leukemia.

Treatment of chronic myeloid leukaemia (CML) is based on tyrosine kinase inhibitors (TKI), whose introduction in 2001 improved the survival rate after 5 years from 40 to 90%. The longevity increase has been accompanied by a higher incidence of cardiovascular events (CVE) that can be explained due to the sum of cardiovascular risk factors (CVRF) together with the secondary effects of the TKI. The effect of the TKI over the blood pressure control is still unknown. An observational cross-sectional study of patients with CML under treatment with TKI (imatinib, dasatinib and nilotinib) was conducted. Blood pressure was analyzed through sphygmomanometer and 24-h ambulatory blood pressure monitoring (ABPM). A total of 73 patients were included, 57 treated with a single line of treatment. 32.9% of the total of individuals under this study showed uncontrolled blood pressure according to the ABPM. The factors related to uncontrolled BP were overweight, dyslipidemia, alcohol use, pulse wave velocity a high/very high cardiovascular risk. The subjects who received treatment with nilotinib did present worse control of their blood pressure in ABPM than those treated with imatinib and dasatinib (p = 0.041). This finding could indicate that an uncontrolled blood pressure is implied in the pro-inflammatory and pro-atherogenic mechanism underlying the development of the cardiovascular disease in those patients under treatment with nilotinib. The ABPM is a useful tool in the diagnosis and treatment of HT, being the reason why it should be included in the assessment of patients with CML whose HT diagnosis proves uncertain.

Severe Refractory Anaemia and Fever of Unknow Origin: Human Parvovirus B19 Reactivation.

Reactivation of human parvovirus B19 is exceptional and characteristic of immunosuppression, with anaemia being the predominant manifestation although pancytopenia and thrombotic microangiopathy may also occur. We describe a patient with a history of diffuse large B-cell lymphoma with pure erythrocyte aplasia due to reactivation of parvovirus B19, who was treated with corticosteroids and immunoglobulins. LEARNING POINTS: Infection with human parvovirus B19 is identified by polymerase chain reaction (PCR) testing of blood and the presence of typical giant proerythroblasts in the bone marrow.Cytomegalovirus infection should be considered in immunosuppressed patients with fever and non-specific symptoms with haematological changes.The treatment of persistent infection in immunosuppressed patients is based on the administration of IV immunoglobulins at high doses.

Progressive cardiovascular disease in a patient under treatment with nilotinib. / Enfermedad cardiovascular progresiva en paciente bajo tratamiento con nilotinib.

The development of cardiovascular disease appears in subjects with several cardiovascular risk factors. However, other agents could be related to the appearance of cardiovascular disease, like chemotherapy drugs. We present a 63 years-old man with very high cardiovascular risk and chronic myeloid leukemia under treatment with nilotinib. Despite a good control of cardiovascular risk factors, he development a severe and accelerated peripheral arterial disease. Peripheral arterial disease occurs in 5-20% patients under treatment with nilotinib and it is more frequently in subjects with several cardiovascular risk factors.

[Study of blood pressure variability in arterial hypertension and relation with glomerular filtration]. / Estudio de la variabilidad de la presión arterial en pacientes con hipertensión arterial y su relación con el filtrado glomerular.

BACKGROUND AND OBJECTIVE: Besides reducing blood pressure, it is important to think about the blood pressure variability that hypertensive patients may present. Indeed, studies suggest that target organ damage is greater in hypertensive people with high blood pressure variability. The purpose of the present study was to determine the blood pressure variability in patients who had not been treated with antihypertensive medication, as well as its relationship with the glomerular filtration. PATIENTS AND METHOD: We included 702 patients with clinical indication for 24h ambulatory blood pressure monitoring. RESULTS: 43.6% of patients had high variability of the blood pressure. These patients had greater levels of 24-h systolic blood pressure, diurnal and night blood pressure and a lower glomerular filtration. The main factors associated with high blood pressure variability were age, years from diagnosis of arterial hypertension, systolic blood pressure and a glomerular filtration smaller than 60ml/min. CONCLUSIONS: A high variability of blood pressure is frequent among hypertensive patients. Since it is not possible to perform ambulatory blood pressure measurement in all them, we should mainly suspect it in old patients and in those with reduced glomerular filtration.

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)

Rivaroxaban: searching the integral vascular protection.

INTRODUCTION: Residual cardiovascular risk remains high in patients with atherosclerotic cardiovascular disease despite current antithrombotic therapy. On the other hand, patients with atrial fibrillation have an increased risk of myocardial infarction and cardiovascular death. As a result, a new antithrombotic approach appears necessary to reduce this risk. Areas covered: In this article, the role of rivaroxaban on vascular protection in patients with cardiovascular disease and/or atrial fibrillation was reviewed, with a particular focus, but not limited, on clinical trials. Expert commentary: Previous data have shown that factor Xa plays a key role in the etiopathogenesis of atherothrombosis. Experimental data suggest that rivaroxaban exhibits antiinflammatory and antioxidative stress properties, and may improve endothelial dysfunction. The COMPASS trial showed that among patients with stable atherosclerotic vascular disease, the addition of rivaroxaban 2.5 mg twice daily (vascular dose) to aspirin provided a higher cardiovascular protection than aspirin alone. In ROCKET-AF trial, compared with warfarin, rivaroxaban 20 mg once daily (15 mg if moderate renal dysfunction) (anticoagulant dose) was, at least, as effective as warfarin for the prevention of stroke or systemic embolism among patients with nonvalvular atrial fibrillation, with a trend toward a reduction in the risk of cardiovascular outcomes. All these data suggest that rivaroxaban might have a vascular protective effect beyond its stroke/systemic embolism preventive activity.

Stress, anger and Mediterranean diet as predictors of metabolic syndrome. / Estrés, ira y dieta mediterránea como factores predictores del síndrome metabólico.

BACKGROUND AND OBJECTIVE: Metabolic syndrome (MetS) is a cluster of metabolic conditions that include abdominal obesity, reduction in cholesterol concentrations linked to high density lipoproteins (HLDc), elevated triglycerides, increased blood pressure and hyperglycaemia. Given that this is a multicausal disease, the aim of this study is to identify the psychological, emotional and lifestyle variables that can have an influence on the different MetS components. PATIENTS AND METHODS: A cross-sectional study with 103 patients with diagnostic criteria for MetS (47 male and 56 female). Anthropometric, clinical and analytical measurements were collected to assess the variables associated with MetS. The main psychological and emotional variables were also assessed. RESULTS: Different multiple linear regression tests were performed to identify which variables were predictive of MetS. The dependent variables were body mass index (BMI), abdominal circumference, HDLc, and quality of life, and the predictive variables were psychological stress, anger and adherence to a Mediterranean diet. The results showed that psychological stress was a predictor of quality of life (ß=-0.55, P≤0). Similarly, anger was a predictor of BMI (ß=0.23, P=.047) and abdominal circumference (ß=0.27, P=.021). As expected, adherence to a Mediterranean diet was a predictor of HDLc (ß=0.2, P=.045) and of quality of life (ß=-0.18, P=.031). CONCLUSIONS: The results confirm a link between adherence to certain dietary habits and lifestyle, however they go one step further and show the importance of psychological and emotional factors like psychological stress and anger in some MetS components.

[Effect of olmesartan medoxomil on arterial stiffness in patients with essential hypertension]. / Efecto del olmesartán medoxomilo en la rigidez de las grandes arterias en pacientes con hipertensión arterial esencial.

BACKGROUND AND OBJECTIVE: Arterial stiffness is one of the early lesions of the arteries in patients with cardiovascular risk factors. Pulse wave velocity (PWV) is one form of measurement of arterial stiffness. The renin-angiotensin system seems to be involved in the inflammatory mechanisms that take place at level of the vascular wall. The aim of this study is to investigate the effect of olmesartan (angiotensin II type 1 receptor antagonist) in the arterial stiffness, measuring the PWV. Another secondary objective is to determine the antihypertensive efficacy with ambulatory blood pressure monitoring (ABPM). PATIENTS AND METHOD: Seventy-one patients with mild-to-moderate essential hypertension were consecutively included. Clinical blood pressure (CBP), ABPM and PWV, automatized measurement between the carotid and femoral arteries using the Complior device (Colson, Paris, France), were determined in a baseline and after 16 weeks of treatment with 10-40 mg of olmesartan. RESULTS: Sixty-four patients completed the study. The mean (standard deviation) age was 48.31 (9.69) years and 44.9% were men. A significant reduction of the PWV was observed. The basal PWV was 10.50 (1.87) m/s and after treatment was 9.26 (1.84) m/s (p < 0.0001). We found only a positive correlation between the decline of PWV and diastolic blood pressure (BP). We could not find such correlation with systolic BP. The reduction degree was higher in the youngest patients where BP decrease was less evident. The BP decreased in a significant way (p < 0.0001) doing so in CBP and in the periods of 24 h, diurnal and nocturnal. CONCLUSIONS: Olmesartan has shown effective to decrease the arterial stiffness, mainly in young patients. This effect seems to be independent of the decrease of the systolic BP. Olmesartan reduces effectively the BP during the 24 h.

[Primary aldosteronism: analysis of a series of 54 patients]. / Hiperaldosteronismo primario: análisis de una serie de 54 pacientes.

BACKGROUND AND OBJECTIVE: The prevalence of primary aldosteronism (PA) has experienced an important increase, and many authors consider this condition as the main cause of secondary hypertension (HT). PATIENTS AND METHOD: Retrospective study of a series of 54 patients having PA who were studied in our Unit between 1999 and 2003. RESULTS: The prevalence of PA was 5.1%. Out of 54 PA cases, 13 corresponded to aldosterone-producing adenomas (APA), 30 to bilateral adrenal hyperplasia (BAH), one was one case of nodular bilateral hyperplasia and another case was a nodular unilateral hyperplasia. In 9 cases, an etiologic diagnosis could not be done. APA were more frequent in women and BAH in men; with regard to sex, no significant differences were found. The blood pressure (BP) was significantly higher in patients with APA compared with BAH patients. In patients with APA, kalemia was significantly lower than in BAH patients. Adrenal CT scan identified 90% of APA, while scintigraphy detected 100% of BAH. Spironolactone therapy significantly decreased the BP in APA and BAH patients, although this fall was higher in patients with APA. CONCLUSIONS: The prevalence of PA was 5.1%. Although the tests used for the screening and diagnosis of PA are controversial, a PA ought to be investigated in all patients with refractory HT, independently of the existence of hypokalemia. Spironolactone is an effective therapy for BAH and it is an adequate option for APA treatment when an adrenalectomy is not viable.