First degree relatives (FDRs) of subjects with early onset of coronary heart disease (CHD) have higher risk of developing cardiovascular disease. We verified early CHD by angiography in the index patients and extensively phenotyped their FDRs to investigate the relationship of traditional and non-traditional cardiovascular risk factors to carotid ultrasound and coronary calcium scoring findings. B-mode carotid ultrasound was used to assess the combined intima-media thickness and plaque burden in 111 FDRs. The biochemical and anthropometrical characteristics of the FDRs were compared with those of healthy controls matched for sex, age, ethnicity and BMI. Odds ratios indicate that FDRs are more likely to have positive carotid ultrasound findings compared to controls; 2.23 (95% CI 1.14 – 4.37) for intima-media thickness and 2.3 (95% CI 1.22 - 4.35) for average total thickness. In multivariate analysis positive carotid ultrasound findings were higher in FDRs independent of age, gender, total cholesterol over HDL-c ratio, systolic blood pressure and smoking but not homocysteine which had higher values in FDRs compared to controls. In conclusion FDRs of patients with angiographically confirmed CHD have higher burden of subclinical atherosclerosis even when considered in the context of traditional risk factors. Coronary artery calcium scoring (CAC), assessed by 64-slice multi-detector computed tomography (MDCT), was used to assess burden of subclinical atherosclerosis in 57 FDRs compared to controls. FDRs have a two-fold increase in risk of having CAC positive findings; odds ratios for the 75th percentile was 1.96 (95%CI 1.04 – 3.67, p<0.05) while for the 90th percentile odds ratio was 2.59 (95% 1.232 – 5.473, p<0.05). In summary, the risk of significant CAC findings, measured by 64-slice MDCT, is two-fold higher in FDRs than controls. These findings correlate highly with carotid ultrasound findings in the same cohort. Different thresholds for CAC may be appropriate when assessing male versus female FDRs. Together increased carotid ultrasound findings and CAC scoring results in FDRs of patients with validated early onset of CHD suggest these imaging techniques as potentially useful tools in cardiovascular risk assessment that will go above and beyond the current diagnostic algorithms.

Orientador: Antonio Sérgio Martins / Banca: Ilda de Godoy / Banca: Terezinha Dalossi Genari / Resumo: Diferenças de classe sócio-econômica contribuem substancialmente para as e-sigualdades SOCIaISda mortalidade. Imaginava~se que as doenças cardiovasculares afetavam preferencialmente pessoas bem sucedidas do ponto de vista profissional, bem lltridas e de escolaridade elevada: não é o que os dados epidemiológicos apontam. São diversificadas e abundantes na literatura mundial, bem como na brasileira as evidências de que as doenças cardiovasculares e a mortalidade decorrente dessas doenças sejam mais freqüentes entre as pessoas de menor nível sócio-econômico. A hipertensão arterial, o diabetes, o hábito de fumar, a dislipidemia, a obesidade, o coolismo, os fatores de risco não tradicionais e o estresse psicossocial são mais freqüentes em indivíduos de menor nível sócio·econômico. A massa ventricular esquerda aumentada é preditora da morbidade e mortalidade cardiovascular independentemente da pressão arterial e de outros fatores de risco. A .pertrofia ventricular também é mais freqüente em pessoas de estratos sociais menos :avorecidos. Dentre os marcadores de nível sócio.econômico, a escolaridade é a que melhor se oorrelaciona com a freqüência e intensidade dos fatores de risco cardiovascular. O presente studo faz uma revisão dos estudos que avaliaram as proposições listadas acima. / Abstract: Socio-economic inequalities can cause mortality inequalities. There were the believe that cardiovascular disease committed rich, educated and well nourished people: it is not the rrue. There are many studies in world-wide and Brazilian literature showing an association tween low socioeconomic leveI and cardiovascular disease and mortality. Arterial hypertension, diabetes, smoke, dyslipidosis, obesity, alcoholism, non~ traditional risk factors and psicossocial stress are more frequent in low socioeconomic leveI. Left ventricular hypertrophy is a predictor of cardiovascular mortality, independent f blood pressure and other risk factors. Left ventricular hypertrophy is more frequent ong poor and low educated people. Among socioeconomic markers, scholarity is the best marker of cardiovascular risk - tors. This paper review the proposallisted above. / Mestre

Made available in DSpace on 2015-12-06T23:47:38Z (GMT). No. of bitstreams: 0 Previous issue date: 2008 / We evaluated the significance of a diagnosis of metabolic syndrome (MetS), as defined by the National Cholesterol Education Program (NCEP) and by the International Diabetes Federation (IDF), in the evaluation of cardiovascular risk in hypertensive patients. The patients were evaluated to identify MetS and any history of cardiovascular disease (CVD). This was a cross-sectional study involving 638 patients, of which 202 (31.7%) had diabetes. The prevalence of MetS was 54.7% when the IDF criteria were used, compared with 45.5% when the NCEP criteria were used (p < 0.05). Using either set of criteria, MetS was associated with type 2 diabetes mellitus (T2DM) (NCEP,OR: 6.8; 95% CI: 4.7-10 and IDF, OR: 8.4; 95% CI: 5.4-13; p < 0.05 for both). We found that, regardless of the diagnostic criteria used, MetS correlated significantly with the risk and history of CVD (NCEP, OR: 2.04; 95% CI: 1.2-3.4; p < 0.05; and IDF, OR: 2.68; 95% CI: 1.5-4.8; p < 0.05), partially caused by the inclusion of patients with diabetes in the sample. In patients without diabetes, MetS diagnosed using the IDF criteria alone was associated with a history of CVD (OR: 2.4; 95% CI: 1.1-5.2; p = 0.029 vs. NCEP criteria, OR: 1.99; 95% CI: 0.9-4.3, p = NS). In patients with T2DM, MetS was not associated with CVD, regardless of the criteria used. We conclude that, among individuals without diabetes, an IDF criteria-based diagnosis of MetS is useful in identifying those at greater risk for cardiovascular disease. Among patients with diabetes, a diagnosis of MetS, regardless of the criteria used, is of little utility in assessing cardiovascular risk. However, a diagnosis of MetS, using either set of criteria, is useful for identifying individuals more likely to develop T2DM. / BV UNIFESP: Teses e dissertações

Made available in DSpace on 2014-06-11T19:23:40Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-12-13Bitstream added on 2014-06-13T20:11:16Z : No. of bitstreams: 1 martin_rss_me_botfm_prot.pdf: 1009886 bytes, checksum: dcae045910a19c9e9a7e1a7d837139ce (MD5) / Fundação para o Desenvolvimento Médico e Hospitalar (Famesp) / Diferenças de classe sócio-econômica contribuem substancialmente para as e-sigualdades SOCIaISda mortalidade. Imaginava~se que as doenças cardiovasculares afetavam preferencialmente pessoas bem sucedidas do ponto de vista profissional, bem lltridas e de escolaridade elevada: não é o que os dados epidemiológicos apontam. São diversificadas e abundantes na literatura mundial, bem como na brasileira as evidências de que as doenças cardiovasculares e a mortalidade decorrente dessas doenças sejam mais freqüentes entre as pessoas de menor nível sócio-econômico. A hipertensão arterial, o diabetes, o hábito de fumar, a dislipidemia, a obesidade, o coolismo, os fatores de risco não tradicionais e o estresse psicossocial são mais freqüentes em indivíduos de menor nível sócio·econômico. A massa ventricular esquerda aumentada é preditora da morbidade e mortalidade cardiovascular independentemente da pressão arterial e de outros fatores de risco. A .pertrofia ventricular também é mais freqüente em pessoas de estratos sociais menos :avorecidos. Dentre os marcadores de nível sócio.econômico, a escolaridade é a que melhor se oorrelaciona com a freqüência e intensidade dos fatores de risco cardiovascular. O presente studo faz uma revisão dos estudos que avaliaram as proposições listadas acima. / Socio-economic inequalities can cause mortality inequalities. There were the believe that cardiovascular disease committed rich, educated and well nourished people: it is not the rrue. There are many studies in world-wide and Brazilian literature showing an association tween low socioeconomic leveI and cardiovascular disease and mortality. Arterial hypertension, diabetes, smoke, dyslipidosis, obesity, alcoholism, non~ traditional risk factors and psicossocial stress are more frequent in low socioeconomic leveI. Left ventricular hypertrophy is a predictor of cardiovascular mortality, independent f blood pressure and other risk factors. Left ventricular hypertrophy is more frequent ong poor and low educated people. Among socioeconomic markers, scholarity is the best marker of cardiovascular risk - tors. This paper review the proposallisted above.

Introdução: Estudos prévios analisaram a associação entre fatores de risco cardiovascular (FRCV) associados ao diagnóstico de demência vascular (DV) provável ou possível. No entanto, não foram encontrados estudos que analisassem a associação entre FRCV e a ocorrência de DV definitiva. Dessa maneira, ainda permanece obscura a associação entre os FRCV e a ocorrência de DV definitiva, ou seja, aquela diagnosticada por meio do exame neuropatológico, no qual se apresenta como padrão ouro. Objetivo: Avaliar a associação entre os FRCV e a ocorrência de DV definitiva, pura e mista. Método: Por meio de um estudo transversal foram analisados 707 casos pertencentes à casuística do Banco de Encéfalos Humanos do Grupo de Estudos em Envelhecimento (BEHGEEC) da FMUSP, que respeitaram os critérios de inclusão. A existência de fatores de risco cardiovascular em vida (Hipertensão Arterial, Diabetes Mellitus, Dislipidemia, Tabagismo, Etilismo, Obesidade e Sedentarismo), reportada por um informante com convivido minimamente semanal durante a autópsia, foi associada ao diagnóstico neuropatológico de demência vascular emitido por um neuropatologista. Modelos de regressão logística (sem e com ajuste para sexo, idade e raça) foram construídos para testar a associação entre os FRCV e o diagnóstico de DV, DV pura e DV mista. Foi testada a capacidade preditiva dos fatores que se mostraram preditores de DV por meio da Curva ROC. Resultados: O sedentarismo foi um preditor independente de DV (OR 1,943; IC95% 1,198 3,151; p= 0,007) e DV pura (OR 3,148; IC95% 1,428 6,941;p= 0,004). A HAS foi um preditor independente de DV mista (OR 2,240; IC95% 1,216 4,126; p= 0.01). O sedentarismo não apresentou boa capacidade preditiva para a DV e DV Pura (AUC = 0,380 e 0,337, respectivamente), assim como a HAS para a DV Mista (AUC = 0,459). Conclusões: Dentre os FRCV o sedentarismo e a HAS foram os que se associaram a um aumento no risco de DV. / Introduction: Previous studies have analyzed the association between cardiovascular risk factors (CVRF) associated with the diagnosis (probable or possible) of vascular dementia (VaD). However, there are no studies that have analyzed the association between CVRF and the occurrence of definitive VaD. The association between CVRF and the occurrence of definite VaD, neuropathologically defined and considered as gold-standard, remains obscure. Objectives: To evaluate the association between CVRF and the occurrence of definitive VaD, pure and mixed. Methods: This is a cross-sectional study which evaluated 707 cases belonging to the Bain Bank of the Brazilian Aging Brain Study Group (BBBABSG) of FMUSP, respecting the inclusion criteria. The history of existence of cardiovascular risk factors in life (hypertension, diabetes mellitus, dyslipidemia, smoking, alcoholism, obesity, and sedentarism) reported by a knowledgeable next-of-kin, with at least weekly contact with the deceased, was associated with the neuropathological diagnosis of vascular dementia reported by a neuropathologist after the autopsy exam. Logistic regression models (with and without adjustment for sex, age and race) were tested to show the association between CVRF and the diagnosis of VaD, pure Vad and mixed VaD. It was also tested the predictive capacity of the factors that proved to be predictors of VaD through the ROC Curve. Results: Sedentary lifestyle was an independent predictor of VaD (OR 1,943, CI 95% 1,198 - 3,151, p = 0.007) and of Pure VaD (OR 3,148, 95% CI, 1.428 - 6.941, p = 0.004). Hypertension was an independent predictor of Mixed VaD (OR 2,240, 95% CI 1,216 - 4,126, p = 0.01). Sedentary lifestyle did not present good predictive capacity for VaD and Pure VaD (AUC = 0.380 and 0.337, respectively), as Hypertension for Mixed DV did not either (AUC = 0.459). Conclusions: Among the CVRF, sedentarism and hypertension were those associated with an increase VaD risk.

Introdução: As doenças cardiovasculares permanecem como a principal causa de morbimortalidade entre as mulheres no Brasil e no mundo. Estratégias de prevenção primária baseadas na detecção dos fatores de risco tradicionais para aterosclerose, têm sido pouco eficazes para reduzir as altas taxas de mortalidade nessa população. O presente estudo tem como objetivo primário detectar e quantificar a presença de aterosclerose na sua fase subclínica, em mulheres climatéricas e pós-menopausadas. Métodos: Foram estudadas 823 mulheres de 45 a 65 anos de idade (idade média 54,3 ± 5,3 anos), no período peri e pós-menopausa, sem doença cardiovascular conhecida, ou em uso de terapia de reposição hormonal, residentes em Recife, Nordeste do Brasil. Todas foram submetidas a avaliação clínica e dosagens bioquímicas, que incluíram os níveis de glicose, lipídios, proteína C-reativa, hormônio folículo-estimulante, adiponectina e aldosterona. Ultrassonografia modo B foi utilizada na avaliação carotídea; medidas da espessura íntima média carotídea (EIMC) foram determinadas na parede posterior da artéria carótida comum (ACC) utilizando-se um \"software\" de leitura automatizada; aterosclerose carotídea foi definida quando da presença de placa carotídea e/ou EIMC > 1mm. Resultados: De 823 mulheres, 10,2% eram fumantes, 58% tinham hipertensão e 9,9% eram diabéticas. A prevalência de doença aterosclerótica subclínica entre a população analisada foi de 12,7%, e a média da EIMC foi de 0,645 ± 0,124 milímetros. Na análise univariada, foram detectadas associações significativas entre presença de aterosclerose carotídea e: a idade (p < 0,001), o fumo (p=0,014), a hipertensão (p=0,002), a pressão arterial sistólica (p=0,003), o colesterol total (p=0,001) e o LDL-colesterol (p=0,001). No modelo ajustado, a idade (p < 0,001), o fumo (p=0,001), a pressão arterial sistólica (p=0,030) e o colesterol total (p=0,008) se correlacionaram de forma significativa e independente com a aterosclerose carotídea. Conclusão: O presente estudo revelou uma alta prevalência de aterosclerose carotídea entre as mulheres brasileiras a partir do climatério. Assim como a idade, os fatores de risco clássicos se correlacionaram de forma independente com aterosclerose carotídea. Esses resultados são de particular relevância, visto que as estratégias para redução do risco cardiovascular são baseadas em modelos de predição de risco onde as mulheres são frequentemente classificadas no grupo de baixo risco cardiovascular. Consequentemente, as oportunidades de envolvê-las mais cedo na prevenção da doença aterosclerótica são muitas vezes perdidas / Aims: Cardiovascular diseases continue to be the main cause of morbidity and mortality among women in Brazil and worldwide. Strategies of primary prevention, based on the detection of traditional risk factors for atherosclerosis, have had a small impact in reducing the high rates of mortality in this population. Therefore, the main purpose of this study was to analyse the prevalence of subclinical carotid atherosclerosis in peri- and postmenopausal women. Methods: We studied 823 peri- and postmenopausal women, 45 to 65 years-old (mean age 54.3±5.3 years), from Recife city, without known cardiovascular disease and hormone therapy utilization. All of them were submitted to a careful medical evaluation, and biochemical analyses that included glucose and lipids levels, C-reactive protein, follicle-stimulating hormone, adiponectin and aldosterone. B-mode ultrasound was utilized for carotid evaluations; intima-media thickness (IMT) measures were determined on the far wall common carotid artery (CCA) with automated reading software; presence of carotid atherosclerosis was defined as either the presence of plaque and/or IMT >= 1.00mm. Results: Of the 823 women, 10.2% were current smokers, 58% had hypertension and 9.9% were diabetics. The prevalence of subclinical atherosclerotic disease among the analyzed population was 12.7%, and the mean CCA-IMT was 0.645±0.124 mm. By univariate analyses, a positive and statistically significant correlation was found between carotid atherosclerosis and age (p < 0.001), current smoker (p=0.014), hypertension (p=0.002), systolic blood pressure (p=0.003), total cholesterol (p=0.001) and LDL cholesterol (p=0.001). In the adjusted model, age (p < 0.001), current smoker (p=0.001), systolic blood pressure (p=0.030) and total cholesterol (p=0.008), remained correlating significantly and independently with carotid atherosclerosis. Conclusion: Our study showed a high prevalence of carotid atherosclerosis among asymptomatic pre- and post-menopausal Brazilian women. As well as age, classic risk factors correlated independently with carotid atherosclerosis. These findings are of particular relevance as strategies for reducing cardiovascular risk are based on risk prediction models in which women are often classified as having low cardiovascular risk, and opportunities for engaging them in prevention at a younger age are very often missed

Aux Antilles, la faible fréquence des coronaropathies pourrait être liée à des facteurs génétiques, ethniques et/ou une distribution spécifique des facteurs de risque cardio-vasculaire (FDRCV). Les propriétés l'ANP (Atrial Natriuretic Peptide) et l'influence de certains polymorphismes de son gène, fréquents dans les populations d'ascendance Africaine pourraient également être en cause. L'analyse des dossiers de 638 patients coronariens consécutifs a mis en évidence une forte prévalence de l'hypertension artérielle et du diabète dans cette population et révélé des différences significatives dans la prévalence des FDRCV entre Afro-Caribéens (AC), Caucasiens et descendants de migrants Indiens. L'analyse angiographique de 420 patients AC a révélé que le diabète était le FDRCV le plus fortement lié à la sévérité des lésions coronaires alors l'obésité apparaissait comme un facteur protecteur. La transfection in vitro, de cellules musculaires lisses artérielles par une construction adénovirale porteuse du gène de l'ANP a entrainé une inhibition de la prolifération et de la migration cellulaire de 31 % et 25% respectivement. In vivo, cet effet s'est traduit par une réduction de 25% de la formation néotimale et de 28% du rapport intima/média dans un modèle d'hyperplasie de carotide de rat. Dans étude transversale incluant 210 sujets diabétiques AC nous avons mis en évidence une association entre le polymorphisme rs5065 (22381>C) du gène de l'ANP et l'existence d'une coronaropatbie. Dans cette étude, l'odds ratio de la présence d'une coronaropathie chez les porteurs de l'allèle mineur de cette mutation (TC/CC) était de 0,50 (0,26- 0,96; P = 0,038). / In Guadeloupe and Martinique, the low frequency ofcoronary artery disease (CAD) could be related to genetic or ethniefactors and/or specifie distribution ofcardiovascular risk factors (CRFs). Atrial Natriuretic Peptide (ANP) properties and influence of sorne of ANP gene polymorphism that are frequent in populations of African descent could also be involved in CAD occurrence. We retrospectively studied 638 consecutive patients with documented CAO and found a high prevalence of hypertension and diabetes in this population. This study also demonstrated significant differences in the prevalence of CRFs between Afro-Caribbean (AC), Caucasians and Indians migrants. The angiographie analysis of420 patients revealed that in AC, diabetes emerged as the strongest CFR related to the severity ofcoronary lesions while obesity appeared as a protective factor. After transfection by an adenoviral construct carrying the ANP gene, vascular smooth muscle cell proliferation stimulated by 10% fetal calf serum was reduced by 31% and migration by 25%. In vivo, in rat carotid artery model ofvascular injury, neointima formation and intima/media ratio was reduced by 25% and 28% respectively. In a cross-sectional study inc1uding 210 AC diabetics we found an association between rs5065 (22381> C) polymorpbism and the presence of coronary artery disease suggesting that the minor allele could have a protective effect against CAD. The odds ratio for the presence ofCAD in carriers ofthe minor allele ofthis mutation (TC / CC) was 0.50 (0.26-0.96, P = 0.038).

Abstract Most women with polycystic ovary syndrome (PCOS) exhibit features of metabolic syndrome, including insulin resistance, abdominal obesity, dyslipidaemia, glucose intolerance and low-grade chronic inflammation, reflected in elevated levels of serum C-reactive protein (CRP), placing these women at increased risk of cardiovascular disease and type 2 diabetes (type 2 DM). The aim of this study was to investigate the effects of two well-known insulin-lowering drugs used in the treatment of type 2 DM, metformin and rosiglitazone, on traditional cardiovascular risk factors and inflammation in women with PCOS. In addition, the impact of rosiglitazone was evaluated as regards clinical, endocrine and metabolic aspects of PCOS. Six-months of metformin treatment in women with PCOS had beneficial effects on levels of CRP, lipid profile and blood pressure, expressed as increased levels of high-density lipoprotein cholesterol (HDL-C), and decreased levels of triglycerides (TGs), decreased ratio of total cholesterol/HDL-C, decreased levels of CRP, and decreased systolic and diastolic blood pressures. Four-month treatment with rosiglitazone in a randomised, double-blind, placebo-controlled study in overweight women with PCOS resulted in significant improvements in menstrual cyclicity, hyperandrogenism, insulin resistance and hyperinsulinaemia. In addition, rosiglitazone decreased levels of markers of low-grade inflammation, CRP and white blood cell (WBC) count, and the liver function marker alanine aminotransferase (ALAT), while having neutral effects on levels of lipids, and blood pressure. In conclusion, metformin treatment, in accordance with the known beneficial metabolic effects of this drug, could be useful in the prevention of cardiovascular complications in women with PCOS. Rosiglitazone represents an alternative treatment for overweight anovulatory women with PCOS. It could be useful in the prevention of type 2 DM in overweight women with PCOS and for those suffering from possible side-effects related to metformin treatment. In addition, alleviation of inflammation and improvement of liver function during rosiglitazone treatment may indicate decreased future risks of cardiovascular diseases and non-alcoholic fatty liver disease (NAFLD).

First degree relatives (FDRs) of subjects with early onset of coronary heart disease (CHD) have higher risk of developing cardiovascular disease. We verified early CHD by angiography in the index patients and extensively phenotyped their FDRs to investigate the relationship of traditional and non-traditional cardiovascular risk factors to carotid ultrasound and coronary calcium scoring findings. B-mode carotid ultrasound was used to assess the combined intima-media thickness and plaque burden in 111 FDRs. The biochemical and anthropometrical characteristics of the FDRs were compared with those of healthy controls matched for sex, age, ethnicity and BMI. Odds ratios indicate that FDRs are more likely to have positive carotid ultrasound findings compared to controls; 2.23 (95% CI 1.14 – 4.37) for intima-media thickness and 2.3 (95% CI 1.22 - 4.35) for average total thickness. In multivariate analysis positive carotid ultrasound findings were higher in FDRs independent of age, gender, total cholesterol over HDL-c ratio, systolic blood pressure and smoking but not homocysteine which had higher values in FDRs compared to controls. In conclusion FDRs of patients with angiographically confirmed CHD have higher burden of subclinical atherosclerosis even when considered in the context of traditional risk factors. Coronary artery calcium scoring (CAC), assessed by 64-slice multi-detector computed tomography (MDCT), was used to assess burden of subclinical atherosclerosis in 57 FDRs compared to controls. FDRs have a two-fold increase in risk of having CAC positive findings; odds ratios for the 75th percentile was 1.96 (95%CI 1.04 – 3.67, p<0.05) while for the 90th percentile odds ratio was 2.59 (95% 1.232 – 5.473, p<0.05). In summary, the risk of significant CAC findings, measured by 64-slice MDCT, is two-fold higher in FDRs than controls. These findings correlate highly with carotid ultrasound findings in the same cohort. Different thresholds for CAC may be appropriate when assessing male versus female FDRs. Together increased carotid ultrasound findings and CAC scoring results in FDRs of patients with validated early onset of CHD suggest these imaging techniques as potentially useful tools in cardiovascular risk assessment that will go above and beyond the current diagnostic algorithms. / Medicine, Faculty of / Pathology and Laboratory Medicine, Department of / Graduate

While the association between blood pressure (BP) and brain health is increasingly strengthened by various clinical and epidemiologic research findings, less is known about the relationship between longitudinal patterns of BP across midlife and their impact on cognitive aging. Therefore, the current project used a large-scale, prospective longitudinal dataset of the Framingham Heart Study to model various long-term BP patterns using traditional methods and a novel machine-learning approach and investigated their impact on the development of dementia, as well as cognitive performance and brain volumes in late life. Study 1 examined intra-individual BP variability (BPV) across midlife and assessed its association with neuropsychological test performance, brain volumetric measures, and the development of dementia in late life. Contrary to previous findings in the elderly population, increased BP variability across midlife was not significantly associated with any brain aging measures. However, greater mean BP across midlife significantly predicted a greater risk of dementia. This finding led to the hypothesis that elevated BP in midlife, rather than BPV, may predict poorer brain and cognitive outcomes in late life. Study 2 investigated a long-term pattern of elevated BP using a cumulative exposure model, which has been well-recognized as a summary measure of longitudinal variation and cumulative burden associated with elevated cardiovascular risk. Consistent with the hypothesis driven from Study 1, elevated values of cumulative BP were associated with increased risk of dementia, along with poorer performance in most cognitive domains and reduced brain volume in areas including frontal, occipital, and temporal regions. Finally, Study 3 capitalized on a machine-learning approach, and namely, the dynamic time warping algorithm, to analyze BP data over the course of midlife using various pattern clusters. Although preliminary in nature, analyses using this novel approach detected various shapes of BP patterns across midlife. Clinical utility of these shapes and advantages of the machine-learning tool in BP research are discussed. Together, the results from these three studies suggest that BP pattern over the course of midlife, especially regarding long-term elevation of BP, is significantly associated with brain aging outcomes in late life.