Showing papers by "Raul D. Santos published in 2013"

Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society

Abstract: Aims The first aim was to critically evaluate the extent to which familial hypercholesterolaemia (FH) is underdiagnosed and undertreated. The second aim was to provide guidance for screening and treatment of FH, in order to prevent coronary heart disease (CHD). Methods and results Of the theoretical estimated prevalence of 1/500 for heterozygous FH, <1% are diagnosed in most countries. Recently, direct screening in a Northern European general population diagnosed approximately 1/200 with heterozygous FH. All reported studies document failure to achieve recommended LDL cholesterol targets in a large proportion of individuals with FH, and up to 13-fold increased risk of CHD. Based on prevalences between 1/500 and 1/200, between 14 and 34 million individuals worldwide have FH. We recommend that children, adults, and families should be screened for FH if a person or family member presents with FH, a plasma cholesterol level in an adult ≥8 mmol/L(≥310 mg/dL) or a child ≥6 mmol/L(≥230 mg/dL), premature CHD, tendon xanthomas, or sudden premature cardiac death. In FH, low-density lipoprotein cholesterol targets are <3.5 mmol/L(<135 mg/dL) for children, <2.5 mmol/L(<100 mg/dL) for adults, and <1.8 mmol/L(<70 mg/dL) for adults with known CHD or diabetes. In addition to lifestyle and dietary counselling, treatment priorities are (i) in children, statins, ezetimibe, and bile acid binding resins, and (ii) in adults, maximal potent statin dose, ezetimibe, and bile acid binding resins. Lipoprotein apheresis can be offered in homozygotes and in treatment-resistant heterozygotes with CHD. Conclusion Owing to severe underdiagnosis and undertreatment of FH, there is an urgent worldwide need for diagnostic screening together with early and aggressive treatment of this extremely high-risk condition.

Transfer of lipids to high-density lipoprotein (HDL) is altered in patients with familial hypercholesterolemia.

Abstract: Objective In familial hypercholesterolemia (FH), the metabolism and anti-atherogenic functions of HDL can be affected by the continuous interactions with excess LDL amounts. Here, lipid transfers to HDL, an important step for HDL intravascular metabolism and for HDL role in reverse cholesterol transport (RCT) were investigated in FH patients. Methods Seventy-one FH patients (39 ± 15 years, LDL-cholesterol = 274 ± 101; HDL-cholesterol = 50 ± 14 mg/dl) and 66 normolipidemic subjects (NL) (38 ± 11 years, LDL-cholesterol = 105 ± 27; HDL-cholesterol = 52 ± 12 mg/dl) were studied. In vitro, lipid transfers were evaluated by incubation of plasma samples (37 °C, 1 h) with a donor lipid nanoemulsion labeled with 3H-triglycerides (TG) and 14C-unesterified cholesterol (UC) or with 3H-cholesteryl ester (EC) and 14C-phospholipids (PL). Radioactivity was counted at the HDL fraction after chemical precipitation of apolipoprotein (apo) B-containing lipoproteins and the nanoemulsion. Data are % of total radioactivity measured in the HDL fraction. Results Transfer of UC to HDL was lower in FH than in NL (5.6 ± 2.1 vs 6.7 ± 2.0%, p = 0.0005) whereas TG (5.5 ± 3.1 vs 3.7 ± 0.9%, p = 0.018) and PL (20.9 ± 4.6 vs 18.2 ± 3.7 %, p = 0.023) transfers were higher in FH. EC transfer was equal. By multivariate analysis, transfers of all four lipids correlated with HDL-cholesterol and with apo A-I. Conclusion FH elicited marked changes in three of the four tested lipid transfers to HDL. The entry of UC into HDL for subsequent esterification is an important driving force for RCT and reduction of UC transfer to HDL was previously associated to precocious coronary heart disease. Therefore, in FH, HDL functions can be lessened, which can also contribute to atherogenesis.

Relation of Hepatic Steatosis to Atherogenic Dyslipidemia

Abstract: Hepatic steatosis is closely associated with the metabolic syndrome. We assessed for an independent association between hepatic steatosis and atherogenic dyslipidemia after adjustment for obesity, physical activity, hyperglycemia, and systemic inflammation. We studied 6,333 asymptomatic subjects without clinical cardiovascular disease undergoing a health screen in Brazil from November 2008 to July 2010. Hepatic steatosis was diagnosed by ultrasound. Atherogenic dyslipidemia was defined using 2 definitions: criteria for (1) metabolic syndrome or (2) insulin resistance (triglyceride/high-densityelipoprotein cholesterol ratio of ‡2.5 in women and ‡3.5 in men). In hierarchical multivariate regression models, we evaluated for an independent association of hepatic steatosis with atherogenic dyslipidemia. Hepatic steatosis was detected in 36% of participants (average age 43.5 years, 79% men, average body mass index 26.3 kg/m 2 ). Subjects with hepatic steatosis had similar levels of low-densityelipoprotein cholesterol, with significantly lower level of high-densitye lipoprotein cholesterol and higher level of triglyceride compared with those without steatosis. Hepatic steatosis remained significantly independently associated with atherogenic dyslipidemia of both definitions (metabolic syndrome [odds ratio 2.47, 95% confidence interval 2.03 to 3.02] and insulin resistance [odds ratio 2.50, 95% confidence interval 2.13 to 2.91]) after multivariate adjustment. Stratified analyses showed a persistent independent association in nonobese subjects, those without metabolic syndrome, those with normal high-sensitivity C-reactive protein, nonalcohol abusers, and those with normal liver enzymes. Hepatic steatosis was significantly associated with atherogenic dyslipidemia independent of obesity, physical activity, hyperglycemia, and systemic inflammation after multivariate adjustment. In conclusion, this adds to the growing body of evidence that hepatic steatosis may play a direct metabolic role in conferring increased cardiovascular

Impact of Fitness Versus Obesity on Routinely Measured Cardiometabolic Risk in Young, Healthy Adults

Abstract: Obesity demonstrates a direct relation with cardiovascular risk and all-cause mortality, while cardiorespiratory fitness demonstrates an inverse relation. In clinical practice, several cardiometabolic (CM) risk factors are commonly measured to gauge cardiovascular risk, but the interaction between fitness and obesity with regard to CM risk has not been fully explored. In this study, 2,634 Brazilian adults referred for employer-sponsored heath exams were assessed. Obesity was defined as body mass index >30 kg/m 2 or waist circumference >102 cm in men or >88 cm in women when body mass index was 25 to 30 kg/m 2 . Fitness was quantified by stage achieved on an Ellestad treadmill stress test, with those completing stage 4 considered fit. Hepatic steatosis was determined by ultrasound. CM risk factors were compared after stratifying patients into 4 groups: fit and normal weight, fit and obese, unfit and normal weight, and unfit and obese. Approximately 22% of patients were obese; 12% were unfit. Fitness and obesity were moderately correlated (ρ = 0.38 to 0.50). The sample included 6.5% unfit and normal-weight subjects and 16% fit and obese subjects. In overweight and obese patients, fitness was negatively associated with CM risk (p

Vertebral bone density by quantitative computed tomography mirrors bone structure histomorphometric parameters in hemodialysis patients.

Abstract: Diagnosing low bone mass is of clinical importance for hemodialysis (HD) patients due to its association with fractures and cardiovascular disease. We investigated whether bone density obtained by quantitative computed tomography (QCT) is associated with the histologically determined bone volume and microarchitecture parameters in HD patients. Twenty-six HD patients were studied. Bone biopsy samples were obtained from the iliac crest and trabecular bone volume, thickness, number and separation were evaluated by histomorphometry. Vertebral trabecular bone density (VTBD) was evaluated by QCT. VTBD correlated positively with trabecular bone volume (r = 0.69, p < 0.001), trabecular thickness (r = 0.45, p = 0.022) and trabecular number (r = 0.62, p < 0.001), and negatively with trabecular separation (r = −0.50, p < 0.01). In the multiple linear regression analysis adjusting for age, gender and diabetes, VTBD remained associated with bone volume by histomorphometry (β = 0.06; 95 % CI 0.02–0.11; p = 0.006; R 2 = 0.49). VTBD measured by QCT mirrored bone volume and microarchitecture parameters obtained by histomorphometry in HD patients.

Relevance of prehypertension as a diagnostic category in asymptomatic adults

Abstract: OBJETIVO: Avaliar a associacao da pre-hipertensao com perfis metabolico, inflamatorio e de risco cardiovascular em individuos assintomaticos. METODOS: Entre 2006 a 2009, 11.011 adultos assintomaticos (media de idade de 43 anos; 22% mulheres) foram submetidos a protocolo de check-up, sendo classificados em 3 grupos: normotensos (pressao arterial 140/90mmHg ou diagnostico previo de hipertensao arterial). Foram avaliados os perfis metabolico e de risco cardiovascular de cada um dos tres grupos. RESULTADOS: A prevalencia de normotensao, prehipertensao e hipertensao foi, respectivamente, de 27,9%, 53,9% e 18,2%. Quando comparados com os individuos normotensos, os pre-hipertensos apresentaram media de idade maior (42,7 versus 40 anos; p 25kg/m2 (OR: 2,48; IC95%: 2,24-2,74), esteatose hepatica (OR: 2,23; IC95%: 1,97-2,53), sindrome metabolica (OR: 3,05; IC95%: 2,67-3,49) e niveis >2mg/L de proteina C-reativa de alta sensibilidade (OR: 1,52; IC95%: 1,35-1,71). CONCLUSAO: A pre-hipertensao esta associada a aumento da prevalencia de sindrome metabolica, esteatose hepatica e inflamacao subclinica.

Statin restores cardiac autonomic response to acute hypoxia in hypercholesterolaemia

Abstract: Background Hypercholesterolaemia may alter cardiovascular autonomic function. We investigated the autonomic cardiovascular regulation during normoxia and hypoxia in familial isolated HC patients with or without statin treatment. Materials and methods Low (LF-RR) and high (HF-RR) components of spectral analysis of RR interval and systolic arterial pressure (LF-SAP) were obtained during 5 min of normoxia and isocapnic hypoxia (10% O2) in 10 normotensive familial HC patients without medication, in seven HC patients after a 12-week treatment period with 40 mg of simvastatin (HC + SVT) and in eight matched normal volunteers (CO). Results The HC patients had significant impairment of cardiac autonomic modulation parameters compared with CO at normoxia, which was maintained or even accentuated during hypoxia; these parameters included lower total variance of RR, increased normalized LF-RR, decreased normalized HF-RR, increased LF-RR/HF-RR ratio, higher LF-SAP component and reduced α index. However, the HC + SVT group had a significant improvement in all parameters: the LF-RR and LF-SAP decreased (indicating a decrease in cardiac and vascular sympathetic activity), the HF-RR increased (indicating an increase in parasympathetic activity) and the spontaneous baroreflex sensitivity improved. These changes were detected at normoxia and were maintained during hypoxia. Conclusions Our data are the first to show that isolated HC is characterized by an increase in cardiac and vasomotor sympathetic drive, a decrease in cardiac vagal modulation and baroreflex impairment during normoxia and hypoxia. In addition, our data suggest that statin treatment has a potential role in restoring the physiological cardiovascular autonomic control at baseline and during cardiovascular challenge.

Abstract 163: The Prevalence of the Metabolically Healthy Obese Phenotype in an Aging Population and its Association with Subclinical Cardiovascular Disease: The Brazilian Study on Healthy Aging

Abstract: BACKGROUND Obese and overweight individuals have been shown to be at higher risk of CVD events than normal weight individuals. Current literature has elucidated a new phenotype, Metabolically Healthy Obese (MHO), with risks of CVD similar to that of normal weight individuals. Few studies have examined the MHO phenotype in an aging population, especially in association with subclinical cardiovascular disease. METHODS The cross sectional study population consisted of 208 individuals (79% Female), age 80 and older (mean age 84±4, range 80-102). Anthropometrics & biochemical parameters were measured. The Adult Treatment Panel definition of metabolic syndrome (MetS), excluding waist circumference, criteria was used to define metabolically healthy ( RESULTS The prevalence of MHO defined by BMI≥25 kg/m2 &/or waist circumference >88cm in women, >102cm in men & having 3mg/dl, Uric Acid >6 mg/dl (p=NS). Gender, total cholesterol, HDL, LDL, triglycerides, and SBP was significantly associated with MHO (p CONCLUSIONS Our results suggest that the MHO phenotype is still seen in octogenarians, but at lower rates than in the general population suggesting MHO may not simply be an intermediary stage, driven by length of spent in the obese state. Those with this phenotype tended to have lower triglycerides, higher HDL, and lower body fat % than their metabolically at risk obese counterparts (p

Imaging biomarkers to track subclinical atherosclerosis in heterozygous familial hypercholesterolemia

Abstract: Heterozygous familial hypercholesterolemia (FH) is characterized by high LDL cholesterol levels and premature coronary heart disease onset. Nonetheless, the course of coronary disease events in heterozygous FH subjects is variable. The presence and severity of subclinical atherosclerosis predicts cardiovascular event onset and may help reclassify the risk of clinical events in the general population. In this review, we discuss the possible use of subclinical coronary, carotid and aortic atherosclerosis testing in heterozygous FH subjects for cardiovascular risk stratification and treatment. Many FH subjects present an increased and precocious burden of subclinical vascular disease in comparison to normolipidemic subjects. These subjects may be at higher risk of cardiovascular events and might deserve more aggressive lipid-lowering treatment. Nevertheless, routine screening of imaging biomarkers for FH subjects in clinical practice remains to be determined in prospective trials.

Abstract 17969: Physical Activity is Associated With Lower Prevalence of Elevated High Sensitivity C-Reactive Protein in Overweight and Obese, but Not in Normal Weight Individuals

Abstract: Background: Obesity and sedentary lifestyles have been associated with increased risk of cardiovascular disease (CVD). However, it is unclear whether the benefit of physical activity (PA) is independent of obesity status. We aimed to assess the impact of physical activity on vascular inflammation in normal weight, overweight and obese individuals. Methods: This large cross-sectional study included 4852 healthy Brazilian participants. Participants were categorized as normal weight ( BMI 30). Physical activity was assessed by International Physical Activity Questionnaire (IPAQ) and was divided into sedentary or active categories for primary analysis and into three categories for secondary analysis (sedentary, little and moderate to severe). Elevated subclinical vascular inflammation was considered a high-sensitivity C-Reactive protein (hs-CRP) level ≥3. Results: In our study population, 39% were normal weight, 45% were overweight and 17% were obese.. The prevalence of hs-CRP≥3 mg/dl across these was 13%, 19%, and 36% respectively (p Conclusion: The effect of physical activity on systemic inflammation is modified by the presence of obesity. Obese and overweight individuals may derive a greater benefit from PA than normal weight individuals in reducing systemic inflammation and CVD risk. Normal weight individuals do not seem to obtain a significant reduction in inflammation from any level of physical activity in our population.