Role of Cardiovascular Imaging in Risk Assessment: Recent Advances, Gaps in Evidence, and Future Directions.

Optimal risk assessment for primary prevention remains highly challenging. Recent registries have highlighted major discrepancies between guidelines and daily practice. Although guidelines have improved over time and provide updated risk scores, they still fail to identify a significant proportion of at-risk individuals, who then miss out on effective prevention measures until their initial ischemic events. Cardiovascular imaging is progressively assuming an increasingly pivotal role, playing a crucial part in enhancing the meticulous categorization of individuals according to their risk profiles, thus enabling the customization of precise therapeutic strategies for patients with increased cardiovascular risks. For the most part, the current approach to patients with atherosclerotic cardiovascular disease (ASCVD) is homogeneous. However, data from registries (e.g., REACH, CORONOR) and randomized clinical trials (e.g., COMPASS, FOURIER, and ODYSSEY outcomes) highlight heterogeneity in the risks of recurrent ischemic events, which are especially higher in patients with poly-vascular disease and/or multivessel coronary disease. This indicates the need for a more individualized strategy and further research to improve definitions of individual residual risk, with a view of intensifying treatments in the subgroups with very high residual risk. In this narrative review, we discuss advances in cardiovascular imaging, its current place in the guidelines, the gaps in evidence, and perspectives for primary and secondary prevention to improve risk assessment and therapeutic strategies using cardiovascular imaging.

Implications for clinical practice from a multicenter survey of heart failure management centers

OBJECTIVES: This observational, cross-sectional study based aimed to test whether heart failure (HF)-disease management program (DMP) components are influencing care and clinical decision-making in Brazil. METHODS: The survey respondents were cardiologists recommended by experts in the field and invited to participate in the survey via printed form or email. The survey consisted of 29 questions addressing site demographics, public versus private infrastructure, HF baseline data of patients, clinical management of HF, performance indicators, and perceptions about HF treatment. RESULTS: Data were obtained from 98 centers (58% public and 42% private practice) distributed across Brazil. Public HF-DMPs compared to private HF-DMP were associated with a higher percentage of HF-DMP-dedicated services (79% vs 24%; OR: 12, 95% CI: 94-34), multidisciplinary HF (MHF)-DMP [84% vs 65%; OR: 3; 95% CI: 1-8), HF educational programs (49% vs 18%; OR: 4; 95% CI: 1-2), written instructions before hospital discharge (83% vs 76%; OR: 1; 95% CI: 0-5), rehabilitation (69% vs 39%; OR: 3; 95% CI: 1-9), monitoring (44% vs 29%; OR: 2; 95% CI: 1-5), guideline-directed medical therapy-HF use (94% vs 85%; OR: 3; 95% CI: 0-15), and less B-type natriuretic peptide (BNP) dosage (73% vs 88%; OR: 3; 95% CI: 1-9), and key performance indicators (37% vs 60%; OR: 3; 95% CI: 1-7). In comparison to non- MHF-DMP, MHF-DMP was associated with more educational initiatives (42% vs 6%; OR: 12; 95% CI: 1-97), written instructions (83% vs 68%; OR: 2: 95% CI: 1-7), rehabilitation (69% vs 17%; OR: 11; 95% CI: 3-44), monitoring (47% vs 6%; OR: 14; 95% CI: 2-115), GDMT-HF (92% vs 83%; OR: 3; 95% CI: 0-15). In addition, there were less use of BNP as a biomarker (70% vs 84%; OR: 2; 95% CI: 1-8) and key performance indicators (35% vs 51%; OR: 2; 95% CI: 91,6) in the non-MHF group. Physicians considered changing or introducing new medications mostly when patients were hospitalized or when observing worsening disease and/or symptoms. Adherence to drug treatment and non-drug treatment factors were the greatest medical problems associated with HF treatment. CONCLUSION: HF-DMPs are highly heterogeneous. New strategies for HF care should consider the present study highlights and clinical decision-making processes to improve HF patient care.

Hipertensão mascarada: qual o verdadeiro risco cardiovascular? / Masked hypertension: what is the real cardiovascular risk?

Entende-se como hipertensão mascarada (HM) a existência de níveis pressóricos aumentados fora do consultório em pessoas supostamente normotensas e não tratadas. A hipertensos medicados, aplica-se a denominação de "hipertensão mascarada não controlada" (HMNC). Estas condições expõem expressivo contingente de indivíduos a um risco não identificado para eventos cardiovasculares. O presente trabalho teve como objetivo realizar uma revisão sistemática da literatura a fim de identificar os principais estudos de associação entre HM, HMNC e o risco de eventos cardiovasculares. De um total de 566 estudos, 19 foram incluídos na revisão. Dentre estes, apenas 4 não documentaram associação entre HM/HMNC e maior risco cardiovascular. Um estudo observou apenas associação com risco de infarto agudo do miocárdio (IAM) e outro apenas com o risco de acidente cerebrovascular (AVC). Os demais 13 estudos mostraram relação entre presença de HM e/ou HMNC e maior risco de eventos cardiovasculares como AVC, IAM e/ou morte. Em conclusão, existe associação entre a presença de hipertensão mascarada e o aumento no risco de eventos cardiovasculares. Alguns fenótipos especialmente vulneráveis e possíveis estratégias diagnósticas são também objeto de discussão.

Masked hypertension (MH) is defined as a normal ambulatory blood pressure, though elevated in the outpatient setting, in supposedly normotensive patients. For hypertensive patients, the term "uncontrolled masked hypertension" (MUCH) applies. Previous data suggest that subjects who present either MH or MUCH may be exposed to higher cardiovascular risk. The authors sought to carry out a systematic review of the literature regarding the association between MH, MUCH and risk of cardiovascular events. Among 566 studies retrieved,19 were included in the review. Only 4 studies did not document an association between MH/MUCH and risk of cardiovascular events. One study found an association only with the risk of acute myocardial infarction (AMI) and another with the risk of cerebrovascular events. The remaining 13 studies revealed a relationship between the presence of MH/MUCH and a higher risk of cardiovascular events such as stroke, AMI and/or death. In conclusion, there is an association between the presence of MH/MUCH and an increased risk of cardiovascular events. Some especially vulnerable phenotypes as well as possible diagnostic strategies are also discussed.

Obstructive sleep apnea in non-dialyzed chronic kidney disease patients: Association with body adiposity and sarcopenia.

OBJECTIVES: Obstructive sleep apnea (OSA) is a risk factor for cardiovascular disease (CVD), the main cause of mortality in chronic kidney disease (CKD). Although the prevalence of OSA in patients with CKD has not been established, a few studies suggest that it is higher than in the general population, potentially increasing the risk for CVD. Obesity increases the risk, whereas sarcopenia has been suggested as a consequence of OSA in the general population. To our knowledge, these associations have not been adequately evaluated in patients with CKD. The aim of this study was to evaluate OSA frequency and its association with total and upper body adiposity and sarcopenia in non-dialyzed CKD patients. METHODS: This cross-sectional study included 73 patients with stages 3b-4 CKD (42 men, 62.9 ± 1.1 y of age). Glomerular filtration rate was estimated by the CKD-Epidemiology Collaboration equation. Patients were assessed for OSA by Watch-PAT200 (apnea-hypopnea index ≥5 events hourly; Itamar Medical), total body adiposity by dual-energy x-ray absorptiometry (DXA) and body mass index (BMI), upper body adiposity by anthropometric parameters and by trunk and visceral fat by DXA, and sarcopenia. RESULTS: OSA frequency was 67% (N = 49). Both total and upper body adiposity were associated with the presence and severity of OSA. In non-obese patients (BMI <30 kg/m2), upper body obesity increased significantly the frequency of OSA. OSA association with sarcopenia was blunted when BMI was included in regression model. CONCLUSIONS: Results from the present study suggest that in non-dialyzed CKD patients OSA is very common and associated with total and upper body obesity, but not with sarcopenia.

Serum Uric Acid Levels are Associated with Cardiometabolic Risk Factors in Healthy Young and Middle-Aged Adults / Os Níveis Séricos de Ácido Úrico estão Associados a Fatores de Risco Cardiometabólico em Adultos Jovens e de Meia-Idade Saudáveis

Abstract Background: Observational studies have highlighted an association between serum uric acid (SUA) levels and cardiovascular risk factors. Despite the growing body of evidences, several studies were conducted in older individuals or in carriers of diseases susceptible to affect SUA levels and cardiometabolic risk markers. Objective: To evaluate the relationship of SUA with body adiposity, metabolic profile, oxidative stress, inflammatory biomarkers, blood pressure and endothelial function in healthy young and middle-aged adults. Methods: 149 Brazilian adults aged 20-55 years, both sexes, underwent evaluation of body adiposity, SUA, fasting glucose and insulin, lipid profile, malondialdehyde (MDA), high sensitivity C-reactive protein (hs-CRP), adiponectin, blood pressure and endothelial function. Endothelial function was assessed by the reactive hyperemia index (RHI) derived from peripheral arterial tonometry method. Participants were allocated in two groups according to SUA levels: control group (CG; n = 130; men ≤ 7 mg/dL, women ≤ 6 mg/dL) and hyperuricemia group (HG; n = 19; men > 7 mg/dL, women > 6 mg/dL). A P-value < 0.05 was considered statistically significant. Results: After adjustment for confounders, participants in HG compared with those in CG displayed higher body mass index (BMI): 34.15(33.36-37.19) vs.31.80 (26.26-34.42) kg/m2,p = 0.008, higher MDA: 4.67(4.03-5.30) vs. 3.53(3.10-4.07) ng/mL, p < 0.0001 and lower RHI: 1.68 ± 0.30 vs. 2.05 ± 0.46, p = 0.03). In correlation analysis adjusted for confounders, SUA was positively associated (p < 0.05) with BMI, waist circumference, LDL-cholesterol, triglycerides and MDA, and negatively associated (p < 0.05) with HDL-cholesterol, adiponectin and RHI. Conclusions: This study suggests that in healthy young and middle-aged adults higher SUA levels are associated with higher body adiposity, unfavorable lipid and inflammatory phenotype, higher oxidative stress and impaired endothelial function.

Resumo Fundamento: Estudos observacionais têm destacado uma associação entre níveis de ácido úrico sérico (AUS) e fatores de risco cardiovascular. Apesar do crescente conjunto de evidências, vários estudos foram realizados em indivíduos mais velhos ou em portadores de doenças passíveis de influenciar os níveis de AUS e marcadores de risco cardiometabólico. Objetivo: Avaliar a relação do AUS com adiposidade corporal, perfil metabólico, estresse oxidativo, biomarcadores de inflamação, pressão arterial e função endotelial em adultos jovens e de meia-idade saudáveis. Métodos: 149 adultos, brasileiros, com idades entre 20 e 55 anos, de ambos os sexos, foram submetidos a avaliação de adiposidade corporal, AUS, glicose e insulina de jejum, perfil lipídico, malondialdeído (MDA), proteína C-reativa ultra-sensível (PCR-us), adiponectina, pressão arterial e função endotelial. A função endotelial foi avaliada pelo índice de hiperemia reativa (RHI) derivado do método de tonometria arterial periférica. Os participantes foram divididos em dois grupos de acordo com os níveis de AUS: grupo de controle (GC; n = 130; homens ≤ 7 mg/dL, mulheres ≤ 6mg/dL) e grupo de hiperuricemia (GH; n = 19; homens > 7mg/dL, mulheres > 6mg/dL). Valor de p < 0,05 foi considerado estatisticamente significativo. Resultados: Após ajuste para fatores de confundimento, os participantes do GH comparados aos do GC apresentaram índice de massa corporal (IMC) mais alto: 34,15 (33,36-37,19) vs. 31,80 (26,26-34,42) kg/m2, p = 0,008, MDA mais alto: 4,67(4,03-5,30) vs. 3,53(3,10-4,07) ng/mL, p < 0,0001 e RHI mais baixo: 1,68 ± 0,30 vs. 2,05 ± 0,46, p = 0,03. Na análise de correlação ajustada para fatores de confundimento, o AUS se associou positivamente (p < 0,05) com IMC, circunferência da cintura, LDL colesterol, triglicérides e MDA, e se associou negativamente (p < 0,05) com HDL colesterol, adiponectina e RHI. Conclusões: Este estudo sugere que, em adultos jovens e de meia-idade saudáveis, níveis mais altos de AUS estão associados a maior adiposidade corporal, fenótipo inflamatório e de lipídios desfavorável, maior estresse oxidativo e função endotelial comprometida.

Serum Uric Acid Levels are Associated with Cardiometabolic Risk Factors in Healthy Young and Middle-Aged Adults.

BACKGROUND: Observational studies have highlighted an association between serum uric acid (SUA) levels and cardiovascular risk factors. Despite the growing body of evidences, several studies were conducted in older individuals or in carriers of diseases susceptible to affect SUA levels and cardiometabolic risk markers. OBJECTIVE: To evaluate the relationship of SUA with body adiposity, metabolic profile, oxidative stress, inflammatory biomarkers, blood pressure and endothelial function in healthy young and middle-aged adults. METHODS: 149 Brazilian adults aged 20-55 years, both sexes, underwent evaluation of body adiposity, SUA, fasting glucose and insulin, lipid profile, malondialdehyde (MDA), high sensitivity C-reactive protein (hs-CRP), adiponectin, blood pressure and endothelial function. Endothelial function was assessed by the reactive hyperemia index (RHI) derived from peripheral arterial tonometry method. Participants were allocated in two groups according to SUA levels: control group (CG; n = 130; men ≤ 7 mg/dL, women ≤ 6 mg/dL) and hyperuricemia group (HG; n = 19; men > 7 mg/dL, women > 6 mg/dL). A P-value < 0.05 was considered statistically significant. RESULTS: After adjustment for confounders, participants in HG compared with those in CG displayed higher body mass index (BMI): 34.15(33.36-37.19) vs.31.80 (26.26-34.42) kg/m2,p = 0.008, higher MDA: 4.67(4.03-5.30) vs. 3.53(3.10-4.07) ng/mL, p < 0.0001 and lower RHI: 1.68 ± 0.30 vs. 2.05 ± 0.46, p = 0.03). In correlation analysis adjusted for confounders, SUA was positively associated (p < 0.05) with BMI, waist circumference, LDL-cholesterol, triglycerides and MDA, and negatively associated (p < 0.05) with HDL-cholesterol, adiponectin and RHI. CONCLUSIONS: This study suggests that in healthy young and middle-aged adults higher SUA levels are associated with higher body adiposity, unfavorable lipid and inflammatory phenotype, higher oxidative stress and impaired endothelial function.

The effects of moderate energy restriction on apnoea severity and CVD risk factors in obese patients with obstructive sleep apnoea.

Nutritional intervention for weight loss is one of the treatment options for obstructive sleep apnoea (OSA) in patients with overweight or obesity. However, the effects of moderate energy restriction on OSA severity are not yet known. The present study aimed to evaluate the effects of moderate energy restriction on OSA severity and CVD risk factors in obese patients with OSA. In this 16-week randomised clinical trial, twenty-one obese subjects aged 20-55 years and presenting an apnoea/hypopnoea index (AHI)≥5 events/h were randomised into two groups: the energy restriction group (ERG) and the control group (CG). The ERG was instructed to follow an energy-restricted diet -3347·2 kJ/d (-800 kcal/d) and the CG was advised not to change their food intake. At the beginning and at the end of the study, participants underwent evaluation of the following: OSA (Watch-PAT200®), nutritional parameters, blood pressure, sympathetic activity, inflammatory biomarkers, metabolic profile and endothelial function. The ERG (n 11), compared with the CG (n 10), had a significantly greater reduction in body weight (Cohen's d=-1·19; P<0·001), in AHI (Cohen's d=-0·95; P=0·04) and in plasma concentrations of adrenaline (Cohen's d=-1·02; P=0·04) as well as a significantly greater increase in minimum O2 saturation (Cohen's d=1·08; P=0·03). Although energy restriction was not associated with significant improvements in CVD risk factors, medium-to-large effect sizes were observed, suggesting that the statistically non-significant difference between groups may be due to the small sample size. This study suggests that in obese patients with OSA, moderate energy restriction is able to reduce the parameters of OSA severity and sympathetic activity.

Efeito da terapia farmacológica anti-hipertensiva sobre densidade capilar e função endotelial microcirculatória / Effect of pharmacological antihypertensive therapy on capillary density and microvascular endothelial function

Hipertensos têm rarefação capilar e disfunção endotelial microcirculatória, tornando-se mais vulneráveis a lesões em órgãos-alvo. O estudo buscou avaliar o efeito de seis meses de tratamento farmacológico sobre densidade capilar e reatividade microvascular a estímulos fisiológicos e farmacológicos em hipertensos de baixo risco cardiovascular. Secundariamente testou-se a existência de diversidade nas respostas a diferentes estratégias anti-hipertensivas. Foram recrutados 44 pacientes, com 46,7±1,3 anos e 20 normotensos com 48,0±1,6 anos. Avaliaram-se dados antropométricos e laboratoriais e dosaram-se no soro o fator de crescimento vascular endotelial (VEGF), receptor Flt-1 para VEGF e óxido nítrico (NO). A contagem capilar foi por microscopia intravital, captando-se imagens da microcirculação no dorso da falange do dedo médio e contando os capilares com programa específico. Repetia-se o procedimento após hiperemia reativa pós-oclusiva (HRPO) para avaliar o recrutamento capilar. A reatividade vascular foi testada por fluxometria Laser Doppler, iontoforese de acetilcolina (Ach), HRPO e hiperemia térmica local (HTL). Os pacientes foram distribuídos aleatoriamente para dois grupos de tratamento: succinato de metoprolol titulado a 100 mg diários ou olmesartana medoxomila titulada a 40 mg diários, empregando-se, se necessário, a hidroclorotiazida. Os controles seguiram o mesmo protocolo inicial e após seis meses todos os testes foram repetidos nos hipertensos. As variáveis clínicas e laboratoriais basais eram semelhantes em comparação aos controles e entre os dois grupos de tratamento. Após seis meses, havia pequenas diferenças entre os grupos na relação cintura-quadril e HDL. A densidade capilar antes do tratamento era significativamente menor que no grupo controle (71,3±1,5 vs 80,6±1,8 cap/mm2 p<0,001 e HRPO 71,7±1,5 vs 79,5±2,6 cap/mm2 p<0,05) e, com o tratamento, aumentou para 75,4±1,1 cap/mm2 (p<0,01) no estado basal e para 76,8±1,1 cap/mm2 à HRPO (p<0,05)...

Capillary rarefaction and microcirculatory endothelial dysfunction are hallmarks of hypertension, rendering patients vulnerable to target organ lesions. The study aimed at assessing the effect of a six-month treatment period upon capillary density and microvascular reactivity to physiological and pharmacological stimuli. In addition, two different treatment strategies were tested for possible differences between effects upon those variables. A total of 44 patients were recruited, mean age 46.7±1.3 years and 20 normotensive individuals served as controls, mean age 48.0±1.6 years. Anthropometrical and laboratory data were collected, as well as plasma levels of vascular endothelial growth factor (VEGF), its receptor Flt-1 and nitric oxide (NO). Capillary density was obtained by intra-vital microscopy of the dorsum of the middle phalanx before and after post-occlusive reactive hyperemia (PORH). Capillary loops were counted by a semi-automated software. Microvascular reactivity was tested by laser Doppler flowmetry (LDF), and the challenges consisted of acetylcholine iontophoresis, local thermal hyperemia (LTH) and PORH. Patients were randomly allocated to either one of two treatment arms: metoprolol succinate uptitrated to 100 mg daily or olmesartan medoxomil uptitrated to 40 mg daily, with addition of hydrochlorothiazide if necessary. Controls underwent the same initial protocol and all tests were repeated in patients after six months. Baseline clinical and laboratory parameters were similar between patients and controls and between the two treatment groups. After six months there were slight, although significant, differences between the two groups in waist/hip ratio and HDL-cholesterol. In the whole cohort, pretreatment capillary density was significantly reduced compared to controls (71.3±1.5 vs 80.6±1.8 cap/mm2 p<0.001 and PORH 71.7±1.5 vs 79.5±2.6 cap/mm2 p<0.05). After treatment it increased to 75.4±1.1 cap/mm2 (p<0.01) at rest and 76.8±1,1 cap/mm2...

Estratificação de risco cardiovascular e metas de terapia anti-hipertensiva: [revisão] / Cardiovascular risk stratification and goals of anti-hypertensive therapy: [review]

Tem sido demonstrada uma relação linear e contínua entre aumento da pressão arterial (PA) e risco de eventos cardiovasculares, mesmo para diferenças de pressão dentro da faixa de normalidade. Como ao menos metade da carga de doenças decorrentes da hipertensão acomete precisamente indivíduos com PA limítrofe, é imperativo reconhecer e tratar mais intensamente aqueles em que a conjunção de fatores de risco os torna mais propensos a um evento cardiovascular. A maior parte do risco atribuível a infarto e acidente vascular cerebral (AVC) deve-se à interação de nove fatores potencialmente modificáveis. As diretrizes internacionais têm concentrado esforços no sentido de definir categorias distintas de risco e metas terapêuticas destinadas a minimizar as chances de um desfecho cardiovascular. Embora sujeitas a críticas, as ferramentas disponíveis para estratificação de risco apoiam-se em dados facilmente coletados e identificam indivíduos com maior potencial de auferir benefícios rápidos da terapia anti-hipertensiva e de outras medidas preventivas. Já existe consenso quanto à recomendação de oferecer terapia medicamentosa àqueles com PA igual ou maior que 140/90 mmHg, mas existem áreas de incerteza em relação ao início de terapia medicamentosa no paciente com PA limítrofe e em idosos hipertensos estágio I. Tampouco encontra suporte nas evidências disponíveis a recomendação de buscar níveis ótimos em vários subgrupos de hipertensos. A definiçãode apenas dois alvos terapêuticos segundo a magnitude do risco cardiovascular, conforme publicado nas VI Diretrizes Brasileiras de Hipertensão, reconhece esses limites e simplifica bastante o processo de decisão terapêutica.

There has been demonstrated a linear and continuous relationship between an increased blood pressure and risk of cardiovascular events, even for differences in blood pressure levels within the so-called normal range. Since at least half the burden of hypertension related diseases affects subjects with borderline blood pressure, it is imperative to recognize and treat more intensively those individuals where the combination of risk factors renders them more prone to a cardiovascular event. A very large proportion of the attributable risk of myocardial infarction and stroke is due to the interaction of nine potentially modifiable factors. International guidelines have concentrated efforts to define distinct categories of risk and establish therapeutic goals to minimize the chances of a cardiovascular outcome. Although vulnerable to criticism, the available tools for risk stratification rely on easily collected data and identify individuals with greater potential to draw rapid benefits from antihypertensive therapy and other preventive measures.There is already consensus regarding the offer of pharmacological therapy to those whose blood pressure equals or exceeds 140/90 mmHg but some uncertainty persists regarding the onset of pharmacological the rapyin elderly with stage I hypertension and borderline hypertensives. Nor there is any support from available evidence, for the recommendation to seek optimal target levels invarious subgroups of hypertensives. The definition of only two therapeutic targets according to the magnitude of cardiovascular risk as published in the VI Brazilian Guidelines on Hypertension recognizes these limitations and greatly simplifies the process of therapeutic decision.