Introdução: Os benefícios dos ácidos graxos poli-insaturados ômega 3 (w-3) no metabolismo lipídico e na saúde cardiovascular são amplamente aceitos. Entretanto, o impacto do w-3 na composição corpórea, na homeostase da glicose e consequente modificação do risco cardiovascular não tem sido foco dos desfechos primários da maioria dos estudos clínicos. Objetivo: Avaliar o impacto da suplementação de w-3 sobre a composição corporal, o controle glicêmico e o nível de risco cardiovascular em indivíduos adultos. Métodos: A partir de uma sub-amostra do estudo CARDIONUTRI (estudo clínico, randomizado, controlado e duplo cego com seguimento de 2 meses) foram selecionados 86 indivíduos (grupo w-6, 3g de óleo de girassol/d) e 88 indivíduos (grupo w-3, 3g de óleo de peixe/d 60 por cento EPA/DHA). O efeito das intervenções foi monitorado nos tempos basal e T=8 (oito semanas). Nestes períodos foram coletadas informações demográficas, clínicas, atividade física, dieta, antropométricas e de composição corporal. Amostras de sangue foram coletadas após jejum de 12h e a partir do plasma/soro foram avaliados glicemia, insulina, colesterol total e associado a LDL e HDL, triacilgliceróis e as apolipoproteína AI e B utilizando métodos comerciais. O nível de risco cardiovascular dos indivíduos foi estimado pelo Escore de Risco de Framingham (ERF). Os resultados do efeito do tempo, da intervenção e das interações entre parâmetros monitorados e os desfechos foram analisados por meio do programa SPSS 20.0, sendo o nível de significância adotado de p<0,05. Resultados: A maioria dos indivíduos inclusos era do sexo feminino e da raça branca, sem diferença entre os grupos. As doenças mais prevalentes em ambos os grupos foram a hipertensão arterial, o diabetes mellitus e as dislipidemias. Não foram observadas mudanças de glicemia e insulina de jejum, HOMA-IR e HOMA 2- por cento S, com a suplementação de w-3, exceto nos indivíduos com risco cardiovascular intermediário, segundo o ERF. Em relação aos parâmetros antropométricos e de composição corporal, a população feminina do grupo w-3 apresentou redução do percentual de massa gorda ao longo do tempo e intervenção, assim como, foi também observada tal redução entre os indivíduos com alto risco cardiovascular. Não foi contatada variação na distribuição do ERF, apesar da melhora de seus componentes (colesterol total e HDL-C). Conclusões: A suplementação com w-3 promoveu redução de insulina e HOMA-IR nos indivíduos com ERF intermediário. Observou ainda efeito benéfico na redução do percentual de gordura corporal entre as mulheres e indivíduos com ERF alto, assim como na diminuição do colesterol total e aumento da HDL-C. / Introduction: The benefits of polyunsaturated omega 3 (n-3) on lipid metabolism and cardiovascular health fatty acids are widely accepted. However, the impact of n-3 in body composition, glucose homeostasis and consequent modification of cardiovascular risk has not been the focus of the primary outcomes of most clinical trials. Aim: To evaluate the impact of n-3 supplementation on body composition, glycemic control and the level of cardiovascular risk in adults. Methods: From a subsample of CARDIONUTRI study were selected (clinical, randomized, controlled, double blind study with follow-up of 2 months) 86 patients (group n-6, 3g of sunflower oil/d) and 88 individuals (n-3 group, 3g fish oil/d - 60 per cent EPA/DHA ). The effect of the interventions was monitored at baseline and T = 8 (eight weeks). In these periods were collected demographic information, clinical, physical activity, diet, anthropometric and body composition. After 12h fasting, blood samples were collected and, from plasma/serum, were evaluated glucose, insulin, total cholesterol, cholesterol associated with LDL and HDL, triacylglycerol, apolipoprotein AI and B using standard methods. The level of cardiovascular risk of individuals was estimated by the Framingham Risk Score (FRS). The results of the effect of the time of the intervention and the interactions between monitored parameters and outcomes were analyzed using the SPSS 20.0 program and the level of significance of p < 0.05. Results: The majority of individuals included were female and white, with no difference between groups. The most prevalent diseases in both groups were hypertension, diabetes mellitus and dyslipidemia. No change was observed in glucose and fasting insulin, HOMA-IR and HOMA 2- per cent S, with supplementation with n-3, except in patients with intermediate cardiovascular risk, according to the FRS. Regarding the anthropometric and body composition parameters, the n-3 group showed a reduction in the percentage of fat mass among females over time and intervention, as was also observed that reduction among individuals at high cardiovascular risk. There was no variation in the distribution of the ERF, despite the improvement of its components (total cholesterol and HDL-C). Conclusions: Supplementation with n-3 promoted reduction of insulin and HOMA-IR in subjects with intermediate FRS. It noted beneficial effect in reducing the percentage of body fat among women and individuals with high FRS, as well as decreased total cholesterol and increased HDL-C.

Introdução: A obesidade se caracteriza como um processo oxidativo e inflamatório, que predispõe adolescentes, de modo precoce, a eventos até recentemente pouco frequentes nessa faixa etária. Assim, a ação da enzima Fosfolipase A associada às lipoproteínas (Lp-PLA ), que reduz fosfolipídios oxidados e gera lisofosfolipídios, bem como a disponibilidade de antioxidantes plasmáticos, representam um importante tema de pesquisa no contexto cardiovascular. Objetivo: Verificar se a atividade da LP-PLA 2 2 e a concentração de antioxidantes lipossolúveis se associam com os principais marcadores de risco cardiovascular em adolescentes. Métodos: Duzentos e quarenta e dois adolescentes (10 a 19 anos), de ambos os sexos foram distribuídos, segundo o índice de massa corporal (IMC), em três grupos: Eutróficos (n=77), Sobrepeso (n=82) e Obesos (n=83). A amostra foi caracterizada através de parâmetros sócio-econômicos, estado de saúde, uso de medicamentos, antedecentes familiares de doenças crônicas e prática de atividade física. Foram avaliados ainda os dados antropométricos (peso, altura e composição corporal - bioimpedância), e o consumo alimentar por meio de três recordatórios 24 h. A partir de uma amostra de sangue coletada após jejum (12h), realizaram-se as análises da atividade da Lp-PLA , LDL(-) e seus auto-anticorpos, perfil lipídico (colesterol total, LDL-C, HDL-C e triglicerídeos), tamanho da HDL, proteína transportadora de éster de colesterol (CETP), ácidos graxos não esterificados (NEFAs), adipocitocinas, assim como antioxidantes (retinol, licopeno, -tocoferol e -caroteno) no plasma. Resultados: Artigo 1: Lp-PLA maybe an important cardiovascular biomarker in obese adolescents. Verificou-se que o perfil lipídico, insulina, HOMA-IR (resistência à insulina) e LDL(-) evidenciaram um maior risco cardiovascular nos adolescentes obesos. A atividade da enzima Lp-PLA 2 mostrou uma variação proporcional ao IMC, circunferência da cintura e porcentagem de gordura. Essa tendência foi, ainda, reforçada pelas associações positivas entre a enzima e HOMA-IR, glicose, insulina e as variáveis lipídicas. Adicionalmente, associação negativa foi encontrada para ApoAI. As associações mais relevantes foram observadas para ApoB e Apo B / Apo AI (=0,293; P<0,001, =0,343; P<0,001, respectivamente). O melhor modelo preditor para a atividade da enzima incluiu Apo B/Apo AI (= 0,327; P<0,001), tamanho da HDL (=-0,326; P<0,001), circunferência da cintura (=0,171; P=0,006) e glicose (= 0,119; P=0,038). A análise de Odds Ratio mostrou que a mudança de uma unidade na razão entre Apo B/Apo AI esteve associada a 73.5 maior risco para elevada atividade de Lp-PLA 2 . Conclusão: A enzima Lp-PLA , em adolescentes, varia em função do estado nutricional e está relacionada a vários marcadores de risco cardiovascular, especialmente a Apo B/Apo AI. Assim, a atividade da enzima pode representar um importante biomarcador de risco cardiovascular na adolescência. Artigo 2: Antioxidant, and inflammatory aspects of phospholipase A 2 associated to lipoprotein (Lp-PLA ): A review. Esta revisão descreve os principais aspectos relacionados à enzima Lp-PLA 2 e seu impacto no perfil inflamatório e oxidativo da doença aterosclerótica. Artigo 3: Plasma antioxidants, but not the dietary ones, are associated with cardiometabolic risk in adolescents. Neste artigo, observou-se que 2 os antioxidantes -caroteno, licopeno, retinol e -tocoferol variam em função do IMC. Verificou-se que -caroteno e -tocoferol apresentaram valores reduzidos para o grupo obeso em comparação ao eutrófico e ao sobrepeso. Para o -caroteno, verificou-se que essa diferença pôde ser observada inclusive quando comparados sobrepesos e eutróficos. Quando esses antioxidantes foram ajustados pelo colesterol total ou pelo LDL-C essas diferenças se mantiveram. Correlações importantes foram obtidas entre os antioxidantes ajustados por colesterol ou por LDL-C e as variáveis de risco cardiometabólico (perfil lipídico (colesterol total e frações, CETP), resistência à insulina (HOMA-IR, insulina, glicose) e LDL(-)). A obesidade representou um importante fator para a existência dessas correlações, pois após o ajuste por IMC foram reduzidas. Apesar desses resultados, os antioxidantes availados pelo recordatório de 24h não apresentaram nenhuma correlação com os fatores de risco cardiometabólico. Conclusão: Antioxidantes plasmáticos estão relacionados ao risco cardiometabólico em adolescentes, sendo que o IMC desempenha um papel importante para a existência dessas correlações. Tais biomarcadores representam uma melhor maneira de estimar a influência de um padrão dietético sobre o risco cardiometabólico em adolescentes do que a avaliação do inquérito alimentar / Introduction: Obesity is characterized as an oxidative and inflammatory process, which precociously predisposes adolescents to events until recently uncommon in this age group. Thus, the action of Lipoprotein-associated phospholipase A (LpPLA ), which reduces oxidized phospholipids and generates lysophospholipids, as well as the availability of plasma antioxidants, represent important subjects of cardiovascular research. Objetive: To evaluate if the activity of Lp-PLA 2 and the concentration of fat-soluble antioxidants are associated with the most important cardiovascular risk markers in adolescents. Methods: 242 adolescents (10 to 19 years old), from both sexes, were distributed according to Body mass index (BMI) in three groups: Health Weigth (HW, n=77), Overweigth (OV, n=82) and Obeses (OB, n=83). The sample was characterized by socioeconomic parameters, health condition, use of medications, family history of chronic diseases and physical activity. It were evaluated also the anthropometric data (weigth, heigth, body composition - bioimpedance) and the food intake through three 24h-recall. From a blood sample collected after fasting (12h), were analized the Lp-PLA activity, the levels of LDL(-) and it antibodies, the lipid profile (total cholesterol, LDL-C, HDL-C and triglycerides), HDL-size, Non-Esterified Fatty Acids (NEFAs), Cholesteryl Ester Transfer Protein (CETP), adipocytokines, as well as plasma antioxidants (retinol, licopene, -tocopherol e -carotene). Results: Article 1: Lp-PLA as an important biomarker of cardiovascular risk in obese adolescents. It was observed that the lipid profile, the insulin, the HOMA-IR (insulin resistance) and the LDL(-) represented a higher cardiovascular risk in obese adolescents. The activity of Lp-PLA 2 has shown a variation proportional to BMI, waist circumference and fat mass percentage. This tendency was reinforced by positive associations of the enzyme with HOMA-IR, glucose, insulin and lipid variables. Additionaly, a negative association was observed for Apo AI. The most relevant associations were observed for ApoB and Apo B / Apo AI (=0,293; P<0,001, =0,343; P<0,001, respectively). The best predictor model for the enzyme activity included Apo B/Apo AI (= 0,327; P<0,001), HDLsize (=-0,326; P<0,001), waist circumference (=0,171; P=0,006) and glucose (= 0,119; P=0,038). The Odds Ratio analysis showed that the change of one unit in the ratio of Apo B/Apo AI was related to a 73.5 times higher risk of elevated Lp-PLA activity. Conclusion: The enzyme Lp-PLA , in adolescents, varies in function of the nutritional status and it is related to several cardiovascular risk markers, especially to Apo B/Apo AI. Thus, this enzyme activity may represent an important biomarker of cardiovascular risk in adolescence. Article 2: Antioxidant and inflammatory aspects of phospholipase A 2 2 associated to lipoprotein (Lp-PLA ): a review. This review describes the main aspects related to the enzime Lp-PLA 2 and its impact to inflammatory and oxidative profiles of atherosclerotic disease. Article 3: Plasma antioxidants, but not the dietary ones, are associated with cardiometabolic risk in 2 adolescents. It was observed that the antioxidants -carotene, licopene, retinol and -tocopherol vary in function of BMI. It was verified that -carotene and - tocopherol presented reduced values for the OB group in comparison with the HW and OV groups. For -carotene, it was observed that this difference was also verified when OB and OV were compared. These differences remained alike when the antioxidants were adjusted by total cholesterol or by LDL-C. Important correlations were obtained between the antioxidants adjusted by total cholesterol or by LDL-C, and cardiometabolic risk variables (lipid profile (total cholesterol and fractions, CETP), insulin resistance (HOMA-IR, insulin, glucose) and LDL(-)). The obesity represented an important factor to the occurrence of these correlations, since they were reduced after BMI adjustment. Despite these results, the antioxidants evaluated by 24h-diet recall did not show any correlations with cardiometabolic risk. Conclusion: Plasma antioxidants are related to cardiometabolic risk in adolescents, where the BMI represents an important factor. These biomarkers are better than the food intake to estimate the influence of a dietary pattern on the cardiometabolic risk in adolescents

Introdução - Evidências recentes de estudos clínicos e epidemiológicos sugerem uma relação inversa entre o consumo de alimentos lácteos e inflamação, demonstrando a relevância do tema para Saúde Pública diante de sua possível atuação na redução do risco cardiovascular. Objetivo - Avaliar a associação entre consumo de alimentos lácteos e marcadores inflamatórios em uma amostra representativa de adultos residentes no município de São Paulo. Métodos - Trata-se de um estudo com delineamento transversal, de base populacional, que utilizará dados bioquímicos (coleta de sangue) e de consumo alimentar (Recordatório Alimentar de 24 horas e Questionário de Frequência Alimentar) provenientes de 269 indiviÍduos de ambos os sexos e idade entre 19 e 59 anos participantes do ISA Capital - 2008/2009. Resultados - Após ajustes de idade e sexo, o consumo total de lácteos demonstrou correlação inversa com as concentrações séricas de homocisteína e interleucina-8. O tercil de maior consumo de iogurte esteve significativamente associado com menores níveis de interleucina-8, fator de necrose tumoral-, homocisteína, triglicérides e VLDL-colesterol e maiores da leptina quando comparado ao tercil de menor consumo (p<0,005). Os queijos com menor teor de gordura apresentaram seu consumo inversamente associado às concentrações de interleucina-8, proteína quimiotática de monócitos-1 e triglicérides e positivamente com HDL-colesterol e leptina, apesar de também correlacionados ao fator de necrose tumoral- e adiponectina (p<0,005). Os grupos do leite e queijos em geral também estiveram associados com alguns marcadores inflamatórios. Conclusões - O maior consumo de iogurte e queijo light parece modular o sistema imune em favor à um menor estado inflamatório, demonstrando-se independentemente associado à reduzidas concentrações de diversos marcadores anti-inflamatórios. Futuros estudos de suplementação poderão confirmar estes achados, caracterizando o benefício do consumo de lácteos. / Introduction - Recent evidence from clinical and epidemiological studies suggest an inverse relationship between dairy consumption and inflammation, which demonstrates the relevance of the subject to Public Health considering its possible role on reducing cardiovascular risk. Objective - To investigate the association between dairy products consumption and circulating levels of inflammatory biomarkers among a representative sample of Brazilian adults from São Paulo City. Methods - The data come from a cross-sectional population-based study, Health Survey for São Paulo (HS-SP). All individuals aged 20 to 59 included in this research gave out completed food consumption information (24-hour dietary recall and Food Frequency Questionnaire) and blood sampling analysis totalizing a 269 subjects sample. Results - After age and gender adjustments, total dairy consumption exhibited an inverse relation with both homocysteine and interleunkin-8. A higher consumption of yogurt was significantly associated with lower levels of interleukin-8, tumor necrosis factor-, homocysteine, triglycerides and VLDL-cholesterol and higher of leptin (p for trend 0.005). Light cheese consumption was inversely associated with concentrations of interleukin-8, monocyte chemoattractant protein-1 and triglycerides and positively with HDL-cholesterol and leptin, despite of being also correlated with tumor necrosis factor- and adiponectin. Milk and cheese also presented significant associations with some inflammatory biomarkers. Conclusions - A higher consumption of yogurt and light cheese seems to modulate immune system in favor of a lower inflammatory status, being independently associated with reduced concentrations of various anti-inflammatory biomarkers. Further research is required to attests these findings, featuring the benefits of dairy consumption.

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

No description available.

Magister Scientiae (Medical Bioscience) - MSc(MBS) / Cardiovascular diseases (CVD) are among the top 10 causes of death in all ages in South Africa. The prevalence of maternal smoking and alcohol consumption during pregnancy is alarmingly high in South Africa. In utero exposure to nicotine and alcohol may cause CVD later in life. There is a global need for early detection of CVD especially those vulnerable during early childhood, to prevent the development of CVD risk factors in adulthood. The aim of this study was to compare CVD risk in five-year-old children from a low socio-economic population with in utero dual exposure to nicotine and alcohol and in utero nicotine exposure by measuring carotid intima-media thickness (cIMT), anthropometric measurements and clinical measurements including blood pressure. A case-control study was conducted on 468 children at five years old through interviews to collect data on demographic characteristics and health statistics. The cIMT was measured using B-mode ultrasonography. Anthropometric measurements were taken such as skinfold thickness, waist circumference, height and weight to calculate Body Mass Index (BMI). Blood pressure measurements such as systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and heart rate (HR) were taken. The data was analysed using SPSS version 26. Descriptive and inferential statistics (Spearman’s correlations, non-parametric partial correlations), Kruskal-Wallis H, Chi-square tests and logistic regression were used for statistical analysis. Results showed a significantly higher right cIMT (RcIMT) (0.36 ± 0.05 mm; P < 0.01) in children with in utero exposure to nicotine and alcohol during pregnancy and a higher RcIMT in males (0.37 ± 0.06 mm; P < 0.01) with in utero dual exposure to nicotine and alcohol when compared to females. A significant association was found between in utero dual exposure to nicotine and alcohol and a high RcIMT, specifically in females at five years old after the adjustment for confounders (B= -1.618, P = 0.002). Consequently, females in the dual exposed group were 7.6 times more likely to exhibit higher RcIMT with a relative risk of 2.6 times greater to children with no exposure. Females also had significantly higher SBP (U= 3829.50, p <0.01), DBP (U= 3527.50, p <0.05), MAP (U= 3561.00, p <0.05) and HR (U= 3887.50, p <0.01) in the dual exposed group. Cardiovascular risk factors were modestly prevalent at five years old in children with in utero teratogen exposures. However, increased adiposity indices were not observed in this population at five years old and were not associated with teratogen exposures. This may indicate that dual exposure to nicotine and alcohol has a significant effect on the intima-media thickness of the carotid arteries in children, but not necessarily on central and peripheral adiposity at five years old. Therefore, CVD risk factors need to be identified early in children in low socioeconomic regions with in utero exposure to nicotine and alcohol to prevent CVD later in life.

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.

Racial disparities in cardiovascular disease (CVD) have become a matter of national concern. We investigated racial disparities and trends in glycosylated hemoglobin, high-density lipoprotein (HDL), C-reactive protein, plasma homocysteine, albuminuria, and other risk factors among 4758 diagnosed hypertensive subjects age 18 years or older from the National Health and Nutrition Examination Survey, 1999-2006. Compared with non-Hispanic whites, Hispanics, and non-Hispanic blacks were more likely to have uncontrolled blood pressure (BP) (Hispanics odds ratio [OR]: 1.58, 95% confidence interval [CI]: 1.21-2.07; blacks OR: 1.42, 95% CI: 0.21-1.67), elevated glycosylated hemoglobin (Hispanics OR: 2.70, 95% CI: 1.89-3.87; blacks OR: 2.17, 95% CI: 1.70-2.77), albuminuria (Hispanics OR: 2.36, 95% CI: 1.71-3.27; blacks OR: 1.80, 95% CI: 1.47-2.20), and less likely to have central obesity (Hispanics OR: 0.68, 95% CI: 0.51-0.91; blacks OR: 0.70, 95% CI: 0.58-0.84). Blacks had lower risks of elevated serum cholesterol (OR: 0.81, 95% CI: 0.67-0.98) and low HDL (OR: 0.76, 95% CI: 0.61-0.94) than whites. The risk of high serum homocysteine was lower in Hispanics and higher in blacks compared with whites (Hispanics OR: 0.64, 95% CI: 0.46-0.90; blacks OR: 1.36, 95% CI: 1.14-1.63). These results highlight the need for targeted interventions to aggressively treat uncontrolled BP, elevated glycosylated hemoglobin in Hispanic and black hypertensive subjects, and high serum homocysteine in blacks, to reduce disparities in CVD risk factors and CVD-associated morbidity and mortality.