Evidence for the involvement of matrix metalloproteinases in the cardiovascular effects produced by nicotine

Nicotine plays a role in smoking-associated cardiovascular diseases, and may upregulate matrix metalloproteinase (MMP)-2 and MMP-9. We examined whether nicotine induces the release of MMP-2 and MMP-9 by rat smooth muscle cells (SMC), and whether doxycycline (non-selective MMP inhibitor) inhibits the vascular effects produced by nicotine. SMC were incubated with nicotine 0, 50, and 150 nM for 48 h. MMP-2 and MMP-9 levels in the cell supernatants were determined by gelatin zymography. The acute changes in mean arterial pressure caused by nicotine 2 mu mol/kg (or saline) were assessed in rats pretreated with doxycycline (or saline). We also examined whether doxcycline (30 mg/Kg, i.p., daily) modifies the effects of nicotine (10 mg/kg/day; 4 weeks) on the endothelium-dependent relaxations of rat aortic rings. Aortic MMP-2 levels were assessed by gelatin zymography. Aortic gelatinolytic activity was assessed using a gelatinolytic activity kit. MMP-2 and MMP-9 levels increased in the supernatant of SMC cells incubated with nicotine 150 nM (P<0.05) but not with 50 nM. Nicotine (2 mu mol/kg) produced lower increases in the mean arterial pressure in rats pretreated with doxycycline than those found in rats pretreated with saline (26 +/- 4 vs. 37 +/- 4 mmHg, respectively; P<0.05). Nicotine impaired of the endothelium-dependent responses to acetylcholine, and treatment with doxycycline increased the potency (pD2) by approximately 25% (P<0.05). While we found no significant differences in aortic MMP-2 levels, nicotine significantly increased gelatinolytic activity (P<0.05). These findings suggest that nicotine produces cardiovascular effects involving MMPs. It is possible that MMPs inhibition may counteract the effects produced by nicotine. (C) 2009 Elsevier B.V. All rights reserved.

New perspectives on the role of aldosterone excess in cardiovascular disease

1. Evidence from recent experimental and clinical studies suggests that excessive circulating levels of aldosterone can bring about adverse cardiovascular sequelae independent of the effects on blood pressure. Examples of these sequelae are the development of myocardial and vascular fibrosis in uninephrectomized, salt-loaded rats infused with mineralocorticoids and, in humans, an association of aldosterone with left ventricular hypertrophy, impaired diastolic and systolic function, salt and water retention causing aggravation of congestion in patients with established congestive cardiac failure (CCF), reduced vascular compliance and an increased risk of arrhythmias (resulting from intracardiac fibrosis, hypokalaemia, hypomagnesaemia, reduced baroreceptor sensitivity and potentiation of catecholamine effects). 2. These sequelae of aldosterone excess may contribute to the pathogenesis and worsen the prognosis of CCF and hypertension. 3. The heart and blood vessels may be capable of extra-adrenal aldosterone biosynthesis, raising the possibility that aldosterone may have paracrine or autocrine (and not just endocrine) effects on cardiovascular tissues. 4. The high prevalence of CCF, which is associated with secondary aldosteronism, and primary aldosteronism (PAL; recently recognized to be a much more common cause of hypertension than was previously thought) argue for an important role for aldosterone excess as a cause of cardiovascular injury. 5. The recognition of non-blood pressure-dependent adverse sequelae of aldosterone excess raises the question as to whether normotensive individuals with PAL, who have been detected as a result of genetic or biochemical screening among families with inherited forms of PAL, are at excess risk of cardiovascular events. 6. Provided that patients are carefully investigated in order to permit the appropriate selection of specific surgical (laparoscopic adrenalectomy for PAL that lateralizes on adrenal venous sampling) or medical (treatment with aldosterone antagonist medications) management and safety considerations for the use of aldosterone antagonists are kept in mind, the appreciation of a widening role for aldosterone in cardiovascular disease should provide a substantially better outlook for many patients with CCF and hypertension.

Avalia����o do risco cardiovascular e fatores associados na popula����o de Anchieta-ES

As doen��as cardiovasculares s��o as principais causas de morte no mundo e muitos constituem os fatores de risco para essas doen��as. Objetiva-se investigar o risco cardiovascular para evento coronariano agudo de acordo com o escore de Framingham em popula����o adulta do munic��pio de Anchieta-ES. Estudo transversal com dados da linha de base do estudo Carmen Anchieta, iniciado em 2010. A amostra foi sistem��tica e estratificada por micro ��rea de abrang��ncia das Unidades de Sa��de da Fam��lia, sexo e idade e 539 pessoas foram selecionadas para este estudo por terem os dados completos. Os dados foram coletados mediante entrevista no domic��lio, exames laboratoriais de sangue, verifica����o da press��o arterial e antropometria nas Unidades de Sa��de. As vari��veis de exposi����o constituem escolaridade, ra��a-cor, renda familiar, resid��ncia em espa��o urbano ou rural, estado civil, consumo de ��lcool, atividade f��sica, ��ndice de massa corp��rea e autoavalia����o de sa��de. Para a classifica����o do risco cardiovascular utilizou-se o escore de Framingham. Foi realizada an��lise bivariada e regress��o log��stica multinomial para testar a hip��tese de associa����o entre as vari��veis e o risco cardiovascular mediante o c��lculo da raz��o de chances (RC) e intervalo de confian��a de 95%. O n��vel de signific��ncia foi p < 0,05. Os resultados mostraram predomin��ncia de pessoas nas faixas et��rias entre 25 a 54 anos, casadas, pardas, ensino fundamental incompleto, baixa renda, insuficientemente ativas, com sobrepeso e obesidade em mais da metade da amostra, 38,6% ingeriam bebida alco��lica e 55,7% relaram sa��de muito boa ou boa. O risco cardiovascular foi baixo em 74%, intermedi��rio em 11,3% e elevado em 14,7%. Estiveram associados ao risco cardiovascular intermedi��rio ser analfabeto 8,89 (3,193-24,756), ter ensino fundamental incompleto 3,17 (1,450-6,964) e ser vi��vo/ separado 2,55 (1,165-5,583) e associados ao risco cardiovascular elevado ser analfabeto 11,34 (4,281-30,049), ensino fundamental incompleto 2,95 (1,362-6,407) e autoavalia����o da sa��de muito ruim/ruim 2,98 (1,072-8,307) e regular 2,25 (1,294-3,925). Ser solteiro constituiu fator de prote����o 0,40 (0,183-0,902).

Preval��ncia de factores de risco de doen��a cardiovascular em estudantes da Escola Superior das Tecnologias da Sa��de do Porto

Realizou-se um estudo observacional descritivo transversal, com 138 indiv��duos seleccionados aleatoriamente em estudantes da ESTSP, de forma a aferir a preval��ncia de factores de risco de doen��as cardiovasculares como a presen��a de hist��ria familiar de doen��a e factores de risco cardiovascular, h��bitos tab��gicos, consumo excessivo de ��lcool, excesso de peso e obesidade, n��veis de actividade f��sica baixa, n��veis excessivos de stress, ansiedade e depress��o, consumo nutricional inadequado, hipertens��o, dislipidemia e diabetes nos mesmos. Na amostra em estudo verificou-se maior preval��ncia de factores de risco relativos �� presen��a de antecedentes familiares (63,0%) e consumo de nutrientes inadequado (100%).

Avalia����o do risco cardiovascular global numa popula����o da zona Norte do Pa��s

As doen��as cardiovasculares lideram as causas de mortalidade em Portugal. Os factores de risco (FR) associados s��o sexo masculino, idade avan��ada, hipertens��o arterial, tabagismo e dislipidemias, cuja sinergia amplifica o risco cardiovascular global (RCG). Realizou-se um rastreio em indiv��duos da regi��o Norte de Portugal, com o objectivo de determinar o RCG, pela tabela derivada do projecto SCORE. Verificou-se excesso de peso e press��o arterial elevada em mais de metade da amostra. Observou-se que RCG passa a alto risco acima dos 50 anos. O RCG permite estimar a interac����o de FR individuais, permitindo definir estrat��gias interventivas, com potenciais ganhos em sa��de.

Prova de esfor��o e factores de risco cardiovascular: um estudo piloto

As doen��as cardiovasculares (DCV���s) s��o a maior causa de mortalidade e morbilidade em Portugal. O seu elevado impacto passa pelo desconhecimento, sub-diagn��stico, elevada preval��ncia e descontrolo dos seus principais factores de risco (cl��ssicos e novos marcadores bioqu��micos). Para o diagn��stico de uma das vertentes da doen��a cardiovascular, a doen��a card��aca isqu��mica, a prova de esfor��o (PE) �� o exame n��o invasivo, de baixo custo, com reduzida taxa de complica����es e de f��cil execu����o, mais usado na cl��nica. O objectivo deste estudo �� averiguar se existe rela����o entre a prova de esfor��o, os factores de risco cardiovascular (FR���s) e alguns dos seus marcadores bioqu��micos. Com vista a alcan��ar objectivo realizou-se um estudo prospectivo, longitudinal e descritivo, na Esferasa��de (Maia), entre Janeiro e Maio de 2011. Foram recolhidos dados, por inqu��rito, referentes a: biografia, antropometria, FR���s, medica����o, PE e an��lises cl��nicas. Tendo sido inclu��dos todos os indiv��duos (idade ��� 18 anos) que tenham realizado prova de esfor��o e an��lises na unidade citada e com diferen��a temporal m��xima de 2 meses, pelo m��todo de amostragem dirigida e intencional. A dimens��o amostral situou-se nos 30 elementos, sendo que 19 eram do g��nero masculino. A m��dia de idade foi 49,43��15,39 anos. Estimou-se a preval��ncia de FR���s e de indiv��duos com valores dos marcadores bioqu��micos anormais. Dois dos indiv��duos apresentavam hist��ria de DCV���s e tr��s deles PE positiva. Foram efectuadas diversas tentativas de associa����o entre as vari��veis integradas no estudo - DCV e FR���s; PE e FR���s; PE e marcadores bioqu��micos; capacidade de esfor��o e FR���s, g��nero e resultado PE. Nenhuma rela����o se revelou significativa, com excep����o para dois casos: rela����o entre as DCV���s e o aparecimento de altera����es na PE (p = 0,002) e associa����o entre PE e colesterol HDL (p=0,040). Para �� de 5%. Conclui-se que n��o existe rela����o aparente entre a prova de esfor��o, a exist��ncia de doen��a cardiovascular, os seus factores de risco e marcadores bioqu��micos.

Efeitos de um programa de exerc��cios espec��fico em indiv��duos integrados num programa de reabilita����o cardiovascular no domic��lio na toler��ncia ao exerc��cio

Introdu����o: As doen��as cardiovasculares s��o a principal causa de morte na Europa e o sedentarismo �� um dos seus principais fatores de risco. Os programas de reabilita����o cardiovascular (RCV) no domic��lio parecem ser eficazes na toler��ncia ao exerc��cio. No entanto, torna-se dif��cil reproduzir um protocolo de exerc��cios no domic��lio, por se tratar de estudos pouco espec��ficos. Objetivo: Avaliar os efeitos de um programa de exerc��cios espec��fico realizado no domic��lio, na toler��ncia ao exerc��cio em pacientes integrados num programa RCV. Metodologia: Estudo quase experimental composto por 20 indiv��duos com pelo menos um ano de enfarte agudo do mioc��rdio, distribu��dos aleatoriamente em dois grupos: grupo experimental (GE) e grupo de controlo (GC), ambos com 10 indiv��duos. O programa de RCV no domic��lio (constitu��do por 10 exerc��cios) teve a dura����o de 8 semanas, com uma frequ��ncia de 3 vezes por semana. Avaliou-se a frequ��ncia card��aca (FC), tens��o arterial e duplo produto basais e m��ximos; FC de recupera����o; equivalentes metab��licos (METs); velocidade; inclina����o; tempo de prova e de recupera����o; ��ndice cif��tico; equil��brio; e tempo em atividade moderada a vigorosa. Resultados: Ao fim de 8 semanas de exerc��cio o GE aumentou significativamente os MET���s (p=0,001), tens��o arterial sist��lica m��xima (p<0,001), duplo produto m��ximo (p<0,001) e tempo de prova (p=0,037) e diminuiu significativamente o tempo de recupera����o (p<0,001), quando comparado com o GC. Conclus��o: O programa de exerc��cios no domic��lio promoveu uma melhoria na toler��ncia ao exerc��cio e parece ter melhorado o equil��brio, para a amostra em estudo.

Effects of irregular-shift work and physical activity on cardiovascular risk factors in truck drivers

OBJECTIVE: To analyze the putative effect of type of shift and its interaction with leisure-time physical activity on cardiovascular risk factors in truck drivers.METHODS: A cross-sectional study was undertaken on 57 male truck drivers working at a transportation company, of whom 31 worked irregular shifts and 26 worked on the day-shift. Participants recorded their physical activity using the International Physical Activity Questionnaire along with measurements of blood pressure, body mass index and waist-hip ratio. Participants also provided a fasting blood sample for analysis of lipid-related outcomes. Data were analyzed using a factorial model which was covariate-controlled for age, smoking, work demand, control at work and social support.RESULTS: Most of the irregular-shift and day-shift workers worked more than 8 hours per day (67.7% and 73.1%, respectively). The mean duration of experience working the irregular schedule was 15.7 years. Day-shift workers had never engaged in irregular-shift work and had been working as a truck driver for 10.8 years on average. The irregular-shift drivers had lower work demand but less control compared to day-shift drivers (p < 0.05). Moderately-active irregular-shift workers had higher systolic and diastolic arterial pressures (143.7 and 93.2 mmHg, respectively) than moderately-active day-shift workers (116 and 73.3 mmHg, respectively) (p < 0.05) as well as higher total cholesterol concentrations (232.1 and 145 mg/dl, respectively) (p = 0.01). Irrespective of their physical activity, irregular-shift drivers had higher total cholesterol and LDL-cholesterol concentrations (211.8 and 135.7 mg/dl, respectively) than day-shift workers (161.9 and 96.7 mg/dl, respectively (ANCOVA, p < 0.05).CONCLUSIONS: Truck drivers are exposed to cardiovascular risk factors due to the characteristics of the job, such as high work demand, long working hours and time in this profession, regardless of shift type or leisure-time physical activity.

Avalia����o do risco cardiovascular numa popula����o da zona Norte do Pa��s

As doen��as cardiovasculares lideram as causas de mortalidade no mundo e em Portugal. Alguns dos fatores de risco (FR) associados s��o sexo masculino, idade avan��ada, hipertens��o arterial, hipercolesteremia, tabagismo, obesidade e sedentarismo, cuja sinergia amplifica o risco cardiovascular. Realizou-se um rastreio em indiv��duos da regi��o norte de Portugal, com o objetivo de determinar, pela tabela derivada do projeto SCORE, o Risco Cardiovascular Absoluto e o Risco Cardiovascular Relativo e Risco Cardiovascular Absoluto Projetado aos 60 anos. Verificou-se a presen��a de v��rios FR na amostra em estudo. A avalia����o do risco permite estimar a intera����o de FR individuais, fundamentando a defini����o de estrat��gias interventivas, com potenciais ganhos em sa��de.

Isolated and synergistic effects of PM10 and average temperature on cardiovascular and respiratory mortality

OBJECTIVE To analyze the effect of air pollution and temperature on mortality due to cardiovascular and respiratory diseases. METHODS We evaluated the isolated and synergistic effects of temperature and particulate matter with aerodynamic diameter < 10 &#181;m (PM10) on the mortality of individuals > 40 years old due to cardiovascular disease and that of individuals > 60 years old due to respiratory diseases in Sao Paulo, SP, Southeastern Brazil, between 1998 and 2008. Three methodologies were used to evaluate the isolated association: time-series analysis using Poisson regression model, bidirectional case-crossover analysis matched by period, and case-crossover analysis matched by the confounding factor, i.e., average temperature or pollutant concentration. The graphical representation of the response surface, generated by the interaction term between these factors added to the Poisson regression model, was interpreted to evaluate the synergistic effect of the risk factors. RESULTS No differences were observed between the results of the case-crossover and time-series analyses. The percentage change in the relative risk of cardiovascular and respiratory mortality was 0.85% (0.45;1.25) and 1.60% (0.74;2.46), respectively, due to an increase of 10 &#956;g/m3 in the PM10 concentration. The pattern of correlation of the temperature with cardiovascular mortality was U-shaped and that with respiratory mortality was J-shaped, indicating an increased relative risk at high temperatures. The values for the interaction term indicated a higher relative risk for cardiovascular and respiratory mortalities at low temperatures and high temperatures, respectively, when the pollution levels reached approximately 60 &#956;g/m3. CONCLUSIONS The positive association standardized in the Poisson regression model for pollutant concentration is not confounded by temperature, and the effect of temperature is not confounded by the pollutant levels in the time-series analysis. The simultaneous exposure to different levels of environmental factors can create synergistic effects that are as disturbing as those caused by extreme concentrations.

CardioBengo study protocol: a population based cardiovascular longitudinal study in Bengo Province, Angola

Background: Cardiovascular diseases and other non-communicable diseases are major causes of morbidity and mortality, responsible for 38 million deaths in 2012, 75 % occurring in low- and middle-income countries. Most of these countries are facing a period of epidemiological transition, being confronted with an increased burden of non-communicable diseases, which challenge health systems mainly designed to deal with infectious diseases. With the adoption of the World Health Organization ���Global Action Plan for the Prevention and Control of non-communicable diseases, 2013���2020���, the national dimension of risk factors for non-communicable diseases must be reported on a regular basis. Angola has no national surveillance system for non-communicable diseases, and periodic population-based studies can help to overcome this lack of information. CardioBengo will collect information on risk factors, awareness rates and prevalence of symptoms relevant to cardiovascular diseases, to assist decision makers in the implementation of prevention and treatment policies and programs. Methods: CardioBengo is designed as a research structure that comprises a cross-sectional component, providing baseline information and the assembling of a cohort to follow-up the dynamics of cardiovascular diseases risk factors in the catchment area of the Dande Health and Demographic Surveillance System of the Health Research Centre of Angola, in Bengo Province, Angola. The World Health Organization STEPwise approach to surveillance questionnaires and procedures will be used to collect information on a representative sex-age stratified sample, aged between 15 and 64 years old. Discussion: CardioBengo will recruit the first population cohort in Angola designed to evaluate cardiovascular diseases risk factors. Using the structures in place of the Dande Health and Demographic Surveillance System and a reliable methodology that generates comparable results with other regions and countries, this study will constitute a useful tool for the surveillance of cardiovascular diseases. Like all longitudinal studies, a strong concern exists regarding dropouts, but strategies like regular visits to selected participants and a strong community involvement are in place to minimize these occurrences.

Desigualdades socioecon��micas na doen��a cardiovascular em Portugal : estudo baseado no 4�� Inqu��rito Nacional de Sa��de

RESUMO - Em Portugal, as doen��as cardiovasculares (DCV), incluindo o acidente vascular cerebral (AVC) e a doen��a card��aca isqu��mica (DCI), s��o das principais causas de morbi-mortalidade e invalidez. Sabe-se que o n��vel socioecon��mico (NSE) influencia o estado de sa��de, todavia s��o escassas as evid��ncias sobre as desigualdades socioecon��micas na DCV em Portugal. O objectivo deste estudo foi analisar a distribui����o da DCV de acordo com o NSE na popula����o portuguesa. Foi realizado um estudo transversal explorat��rio-descritivo usando a base de dados do 4�� Inqu��rito Nacional de Sa��de, 2005/06. As desigualdades socioecon��micas nas DCV, AVC e DCI, factores de risco [sedentarismo, hipertens��o arterial (HTA), diabetes mellitus (DM), tabagismo, obesidade e sofrimento psicol��gico (Mental Health Inventory ��� 52)] e n��mero de consultas m��dicas, foram analisadas atrav��s dos odds ratio por NSE (rendimento familiar equivalente, escala modificada da OCDE) com intervalo de confian��a de 95% e dos ��ndices e curvas de concentra����o. Dos 21 807 indiv��duos, 53,34% s��o do sexo feminino, a idade m��dia �� de 54��11 e entre 35 e 74 anos. A DCV, a DCI, o AVC, a HTA, a DM e a obesidade est��o associados com NSE mais baixos, o tabagismo est�� associado aos NSE mais elevados, enquanto o sedentarismo, o n��mero de consultas m��dicas e o sofrimento psicol��gico n��o apresentam associa����o significativa com o NSE. Os resultados revelam a associa����o entre os estilos de vida, morbilidade e NSE e demonstram que s��o necess��rias pol��ticas de sa��de mais abrangentes, de acordo com as caracter��sticas individuais, culturais e socioecon��micas e dirigidas �� promo����o da sa��de e preven����o da doen��a. -------------------------------------------- ABSTRACT - Cardiovascular diseases (CVD), including stroke and ischemic heart disease (IHD), are the leading causes of morbidity, mortality and disability in Portugal. It is known that socioeconomic status (SES) influences health status; however there is little evidence about socioeconomic inequalities in CVD in Portugal. The aim of this study was to analyze the distribution of CVD according to SES in the Portuguese population. We conducted a cross-sectional descriptive exploratory study using the database of the 4th National Survey of Health, 2005/06. Socioeconomic inequalities in CVD, stroke, IHD, risk factors [physical inactivity, arterial hypertension (AHT), diabetes mellitus (DM), smoking, obesity and psychological distress (Mental Health Inventory ��� 52)], as well as the number of medical visits, were analyzed by SES (family income using the OECD modified equivalent scale) using odds ratio (confidence interval = 95%), and concentration curves and indices. Of the 21 807 individuals, 53.34% are female, aged between 35 and 74 with mean 54 �� 11 years. CVD, IHD, stroke, AHT, MD and obesity are associated with lower SES, smoking is associated with higher SES, while physical inactivity, number of medical visits and psychological distress showed no significant association with SES. Results suggest an association between lifestyle, morbidity and SES. They also demonstrate the need for comprehensive health strategies, involving health promotion and disease prevention, that incorporate individual, cultural and socioeconomic characteristics.

Mortality due to cardiovascular disease in women during the reproductive age (15 to 49 years), in the State of S��o Paulo, Brazil, from 1991 to 1995

OBJECTIVE: To describe mortality due to cardiovascular diseases in women during the reproductive age (15 to 49 years) in the state of S��o Paulo, Brazil, from 1991 to 1995. METHODS: A list of all deaths and their underlying causes, coded according to the International Classification of Diseases, 9th revision, multiple causes of death, and estimates of the female population according to age groups were provided by the SEADE Foundation. Specific coefficients for 100 thousand women for each year as well as the medians of these coefficients related to 5 years, and the percentage of death by subgroups were calculated. RESULTS: Cerebrovascular diseases have the highest coefficients (14.24 for 100 thousand females), followed by ischemic heart disease (7.37), other heart diseases (6.39), hypertensive disease (3.03), chronic rheumatic heart disease (1.58), pulmonary vascular diseases (1.29), and active rheumatic fever (0.05). Systemic arterial hypertension, as an associated cause, occurred in 55.3% to 57.8% of all the deaths due to intracerebral hemorrhage and in 30.4% to 30.8% due to subarachnoid hemorrhage. CONCLUSION: The significance of cerebrovascular diseases, coronary artery disease, and systemic arterial hypertension as causes of mortality suggests the need to emphasize preventive actions for young women who have the potential to reproduce to avoid possible complications in future pregnancies, and premature mortality.

Food consumption of adolescents. A simplified questionnaire for evaluating cardiovascular risk

OBJECTIVE: To develop a simplified questionnaire for self-evaluation by adolescents of foods associated with the risk of coronary diseases. METHODS: Frequency questionnaires about 80 foods were answered by representative samples of 256 adolescents aged 12 to 19 from Rio de Janeiro as part of the Nutrition and Health Research project. The dependent variable was the serum cholesterol predicting equation as influenced by diet, and the independent variables were the foods. The variables were normalized and, using Pearson's correlation coefficient, those with r>0.10 were selected for the regression model. The model was analyzed for sex, age, random sample, and total calories. Those food products that explained 85% of the cholesterol variation equation were present in the caloric model, and contained trans fatty acids were selected for the questionnaire. RESULTS: Sixty-five food products had a statistically significant correlation (P<0.001) with the dependent variable. The simplified questionnaire included 9 food products present in all tested models: steak or broiled meat, hamburger, full-fat cheese, French fries or potato chips, whole milk, pies or cakes, cookies, sausages, butter or margarine. The limit of the added food points for self-evaluation was 100, and over 120 points was considered excessive. CONCLUSION: The scores given to the food products and the criteria for the evaluation of the consumption limits enabled the adolescents to get to know and to balance their intake.