Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / Trata-se de um estudo transversal sobre adesÃo ao tratamento da hi-pertensÃo e seus determinantes, realizado de novembro de 1997 a fevereiro de 1998, com 177 pacientes selecionados aleatoriamente e entrevistados apÃs a con-sulta mÃdica no ambulatÃrio do Hospital de Messejana, Fortaleza-CE. Tais pacien-tes foram visitados em domicÃlio para continuidade da entrevista e contagem de comprimidos, a primeira vez entre 13 e 25 dias apÃs a consulta e a segunda vez entre 13 e 25 dias apÃs a primeira visita. A maior parte (65,8%) dos medicamentos prescritos nÃo foi dispensada no hospital e destes 22,3% nÃo foram adquiridos em outro lugar, portanto 14,7% dos medicamentos prescritos nÃo foram adquiridos pe-los pacientes. A taxa de adesÃo determinada no presente estudo, pelo mÃtodo de entrevista, foi de 62,1%, e pelo mÃtodo contagem de comprimidos, foi de 38,4%. De acordo com o teste de Kappa, o grau de concordÃncia entre os dois mÃtodos foi muito baixo (33,68%). O desempenho da entrevista como uma medida de adesÃo teve as seguintes caracterÃsticas: baixa sensibilidade (52,3%) para detectar pacien-tes nÃo aderentes, alta especificidade (85,3%) para detectar pacientes aderentes, alto valor preditivo (85,1%) para a nÃo adesÃo e baixo valor preditivo (52,7%) para a adesÃo. Devido o baixo desempenho da entrevista para determinar adesÃo, os re-sultados apresentados referem-se ao mÃtodo contagem de comprimidos. As variÃ-veis que se mostraram significantes atravÃs do teste de Fisher (p < 0,15) na anÃlise univariada em relaÃÃo a uma maior adesÃo ao tratamento, foram analisadas para identificar efeitos independentes atravÃs de um modelo de regressÃo logÃstica. Na anÃlise multivariada, maior renda familiar e a ajuda que o paciente recebe da famÃlia para tomar os medicamentos favoreceram uma maior adesÃo ao tratamento (OR = 3,19 - IC [1,01 - 10,04] e OR = 3,00 - IC [1,16 - 7,74], respectivamente). Os resulta-dos tambÃm sugerem como fatores que dificultam a adesÃo dos pacientes ao tra-tamento: nÃmero reduzido de consultas/ano por paciente, grande intervalo entre as consultas, deficiÃncias na orientaÃÃo mÃdica durante a consulta, desabastecimento de medicamentos no hospital e pouco envolvimento dos pacientes no programa de apoio ao paciente hipertenso.

<p>During the past decades the knowledge concerning risk factors and pathophysiology of coronary heart disease (CHD) has substantially increased. However, despite identification of important risk factors CHD remains the leading cause of death in the western world.</p><p>The metabolic syndrome is a cluster of metabolic disorders such as hypertension, hypertriglyceridemia, low HDL-cholesterol, and glucose intolerance associated with an increased risk of cardiovascular morbidity and mortality.</p><p>The studies in this thesis are epidemiological in their character, and examine the relationships between different aspects of CHD and the metabolic syndrome in a population-based study of middle-aged men (ULSAM).</p><p>The findings indicated that serum lipids were important risk factors for the development of both angina pectoris demanding revascularisation and acute myocardial infarction (MI). Proinsulin and blood pressure were independent predictors of MI only, suggesting these factors to be involved in thrombosis and plaque rupture. </p><p>It was also found that antihypertensive treatment with beta-blockers and thiazide diuretics resulted in increased fasting blood glucose concentrations in subjects with an insulin resistant state with elevated proinsulin concentrations. Both proinsulin concentrations and increase in fasting blood glucose were associated with increased risk of developing future MI. </p><p>The finding of a new Q/QS-pattern on the resting ECG, regardless of history of MI, was associated with impaired insulin secretion and was an independent predictor of total and cardiovascular mortality. </p><p>A risk prediction score for MI including proinsulin and the ratio between apolipoprotein B and apolipoprotein A1 was developed in middle-aged men. This score was predictive for future fatal and nonfatal MI, and proved to be at least as good as the Framingham and the PROCAM scores, being based on traditional risk factors.</p><p>In summary these studies provide further knowledge about the associations between CHD and the metabolic syndrome and the possible importance of new markers of cardiovascular risk such as proinsulin and the apolipoproteins.</p>

During the past decades the knowledge concerning risk factors and pathophysiology of coronary heart disease (CHD) has substantially increased. However, despite identification of important risk factors CHD remains the leading cause of death in the western world. The metabolic syndrome is a cluster of metabolic disorders such as hypertension, hypertriglyceridemia, low HDL-cholesterol, and glucose intolerance associated with an increased risk of cardiovascular morbidity and mortality. The studies in this thesis are epidemiological in their character, and examine the relationships between different aspects of CHD and the metabolic syndrome in a population-based study of middle-aged men (ULSAM). The findings indicated that serum lipids were important risk factors for the development of both angina pectoris demanding revascularisation and acute myocardial infarction (MI). Proinsulin and blood pressure were independent predictors of MI only, suggesting these factors to be involved in thrombosis and plaque rupture. It was also found that antihypertensive treatment with beta-blockers and thiazide diuretics resulted in increased fasting blood glucose concentrations in subjects with an insulin resistant state with elevated proinsulin concentrations. Both proinsulin concentrations and increase in fasting blood glucose were associated with increased risk of developing future MI. The finding of a new Q/QS-pattern on the resting ECG, regardless of history of MI, was associated with impaired insulin secretion and was an independent predictor of total and cardiovascular mortality. A risk prediction score for MI including proinsulin and the ratio between apolipoprotein B and apolipoprotein A1 was developed in middle-aged men. This score was predictive for future fatal and nonfatal MI, and proved to be at least as good as the Framingham and the PROCAM scores, being based on traditional risk factors. In summary these studies provide further knowledge about the associations between CHD and the metabolic syndrome and the possible importance of new markers of cardiovascular risk such as proinsulin and the apolipoproteins.

Background High blood pressure is associated with an increased risk of cardiovascular disease and premature death. The shape of association between blood pressure and the risk of cardiovascular events is debated. Some researchers suggest that the association is linear or log-linear, whereas others suggest it is J-shaped. Randomized controlled trials of antihypertensive treatment have been successful in hypertension, but ambiguous in the high normal blood pressure range. Previous systematic reviews have not found any interaction between baseline systolic blood pressure and treatment effect, with beneficial effects at systolic blood pressure levels well below what is currently recommended. These reviews, however, use a method to standardize treatment effects and study weights according to within-trial blood pressure differences that may introduce bias. Methods We performed two systematic reviews to assess the effect of antihypertensive treatment on cardiovascular disease and mortality at different blood pressure levels. The first review was limited to people with diabetes mellitus. The second review included all patient categories except those with heart failure and acute myocardial infarction. Both reviews were designed with guidance from Cochrane Collaborations Handbook for Systematic Reviews of Interventions, and are reported according to PRISMA guidelines. We included randomized controlled trials assessing any antihypertensive agent against placebo or any blood pressure targets against each other. Results were combined in random-effects meta-analyses, stratified by baseline systolic blood pressure. Non-stratified analyses were performed for coronary heart disease trials and post-stroke trials. Interaction between blood pressure level and treatment effect was assessed with Cochran’s Q in the first review, and multivariable-adjusted metaregression in the second review. The third paper builds on data from the second paper, and assesses the effect of standardization according to within-trial blood pressure differences on the results of meta-analyses. We performed non-standardized analyses, analyses with standardized treatment effects, and analyses with standardized treatment effects and standard errors. We compared treatment effect measures and heterogeneity across different methods of standardization. We also compared treatment effect estimates between fixed-effects and random-effects meta-analyses within each method of standardization. Lastly, we assessed the association between number of events and study weights, using linear regression. Results Forty-nine trials assessed the effect of antihypertensive treatment in people with diabetes mellitus. Treatment effect on cardiovascular mortality and myocardial infarction decreased with lower baseline systolic blood pressure. Treatment reduced the risk of death and cardiovascular disease if baseline systolic blood pressure was 140 mm Hg or higher. If baseline systolic blood pressure was below 140 mm Hg, however, treatment increased the risk of cardiovascular death by 15 % (0-32 %). Fifty-one trials assessed the effect of antihypertensive treatment in primary prevention. Treatment effect on cardiovascular mortality, major cardiovascular events, and heart failure decreased with lower baseline systolic blood pressure. If baseline systolic blood pressure was 160 mm Hg or higher treatment reduced the risk of major cardiovascular events by 22 % (95 % confidence interval 13-30 %). If systolic blood pressure was 140-159 mm Hg treatment reduced the risk by 12 % (4-20 %), whereas if systolic blood pressure was below 140 mm Hg, treatment effect was neutral (4 % increase to 10 % reduction). All-cause mortality was reduced if systolic blood pressure was 140 mm Hg or higher, with neutral effect at lower levels. Twelve trials compared antihypertensive treatment against placebo in people with coronary heart disease. Mean baseline systolic blood pressure was 138 mm Hg. Treatment reduced the risk of major cardiovascular events by 10 % (3-16 %), whereas the effect on mortality was neutral (7 % increase to 11 % reduction). Standardization of treatment effects resulted in more extreme effect estimates for individual trials. This caused increased between-study heterogeneity, and different results with fixed- and random-effects model. Standardization of standard errors shifted weights from trials with many events to trials with large blood pressure differences. This caused biased overall effect estimates. Standardization of standard errors also resulted in wider confidence intervals, masking the previously increased heterogeneity. This reduced the possibility to find different treatment effects at different blood pressure levels. Conclusion The effect of antihypertensive treatment depends on blood pressure level before treatment. Treatment reduces the risk of death and cardiovascular disease if baseline systolic blood pressure is 140 mm Hg or higher. Below this level, treatment is potentially harmful in people with diabetes, has neutral effect in primary prevention, but might offer additional protection in people with coronary heart disease. Standardization should generally be avoided in meta-analyses of antihypertensive treatment. Previous meta-analyses using standardized methods should be interpreted with caution. / Hjärt-kärlsjukdomar leder till fler dödsfall och fler förlorade levnadsår än någon annan sjukdomsgrupp. Den enskilt viktigaste riskfaktorn som bidrar till hjärtkärlsjukdomar ur ett befolkningsperspektiv är högt blodtryck. Risken att drabbas av hjärt-kärlsjukdomar minskar om man behandlar högt blodtryck men till vilken nivå blodtrycket skall behandlas är kontroversiellt. Denna avhandling innefattar två systematiska översikter och meta-analyser samt ett arbete som jämför olika sätt att hantera skillnader mellan studier i meta-analyser. De systematiska översikterna sammanställer data från randomiserade kontrollerade studier av blodtryckssänkande behandling. Vår övergripande frågeställning var om effekten av behandling påverkas av blodtrycksnivån innan behandling. Mer specifikt studerades hur behandling påverkade risken att dö eller drabbas av hjärt-kärlsjukdom vid olika blodtrycksnivåer. Det första arbetet fokuserade på personer med diabetes. För dessa fann vi att blodtryckssänkande behandling minskar risken att dö eller drabbas av hjärtkärlsjukdom vid nivåer ≥ 140 mmHg. Vi fann ingen nytta, men möjligen en skadlig effekt av behandling, vid lägre blodtrycksnivåer. Det andra arbetet inkluderade studier oberoende av vilka sjukdomar deltagarna hade. Vi fann att den förebyggande effekten av blodtryckssänkande behandling berodde på blodtrycksnivån. Vid blodtryck &gt; 160 mmHg minskade risken att drabbas av hjärt-kärlsjukdomar med 22 % hos de som erhöll behandling. Om blodtrycket var 140-160 mmHg minskade risken med 12 %, men om blodtrycket var &lt; 140 mmHg sågs ingen behandlingseffekt. Hos personer med känd kranskärlssjukdom, och ett medelblodtryck på 138 mmHg, fann vi en något minskad risk för hjärt-kärlhändelser med ytterligare behandling. I det tredje arbetet fann vi att skillnader i resultat mellan olika studier inte kan antas bero endast på olika grad av blodtryckssänkning i studierna. När resultaten standardiserades, som om alla studier hade sänkt blodtrycket lika mycket, ökade nämligen skillnaderna mellan studierna. Detta resulterade i sin tur i snedvridning av resultaten från meta-analyser av standardiserade värden. Sammanfattningsvis minskar blodtryckssänkande behandling risken att dö eller drabbas av hjärt-kärlsjukdomar om blodtrycket är 140 mmHg eller högre. Vid lägre nivåer är nyttan med behandling osäker samtidigt som det finns potentiella risker. Standardisering bör inte användas rutinmässigt vid metaanalyser av blodtrycksstudier. Tidigare meta-analyser som använt denna metod bör tolkas med försiktighet.

<p>The aim with this thesis was to study cardiovascular disease and hypertension, use of drugs and health from an epidemiological perspective. Various methods - self-rated health (SRH), health related quality of life (HRQL) - the 36-item short form questionnaire (SF-36) - and health utility measurements - the rating scale (RS) and the time-trade off (TTO) methods - were employed.</p><p>Data from the Swedish Adoption/Twin Study of Aging (SATSA) in 1984, 1987, 1990, and 1993 as well as a general population survey conducted in Uppsala County in 1995 were used.</p><p>Persons who have cardiovascular disease, both with and without drug treatment, were found to have a lower SRH as compared to others in the population. Longitudinal analyses showed that SRH was relatively stable over time among persons with cardiovascular disease. Both having a low SRH and having cardiovascular disease were associated with a higher mortality rate.</p><p>Hypertensives were found to have a lower HRQL than do others in the general population as measured by the SF-36. The lowest scoring was found in the general health perception scale (GH), whereas role emotional (RE) and mental health (MH) were the scales least affected by hypertension.</p><p>Nearly 20 percent of the antihypertensive drug users reported side effects.The pattern of side effects was similar to that reported in clinical trials. Both hypertension itself and the drug treatment were found to have an impact on the patient's health-state utility as measured by the RS. Comparative analyses showed that health utilities and psychometric quality-of-life instruments were only moderately correlated among hypertensives. </p><p>The results also showed that inequalities in HRQL were present with respect to several sociodemographic factors. </p><p>In summary, this thesis revealed that persons with cardiovascular disease and/or with hypertension experience poorer health than others in the population. The poor health may be caused both by the disease and/or the drug treatment. The results in this thesis also suggested that special attention and care should be directed to persons with cardiovascular disease and/or hypertension reporting ill health. This especially is important given that low HRQL can be a riskfactor for subsequent cardiovascular events or complications which in turn might result in higher mortality rate.</p>

The aim with this thesis was to study cardiovascular disease and hypertension, use of drugs and health from an epidemiological perspective. Various methods - self-rated health (SRH), health related quality of life (HRQL) - the 36-item short form questionnaire (SF-36) - and health utility measurements - the rating scale (RS) and the time-trade off (TTO) methods - were employed. Data from the Swedish Adoption/Twin Study of Aging (SATSA) in 1984, 1987, 1990, and 1993 as well as a general population survey conducted in Uppsala County in 1995 were used. Persons who have cardiovascular disease, both with and without drug treatment, were found to have a lower SRH as compared to others in the population. Longitudinal analyses showed that SRH was relatively stable over time among persons with cardiovascular disease. Both having a low SRH and having cardiovascular disease were associated with a higher mortality rate. Hypertensives were found to have a lower HRQL than do others in the general population as measured by the SF-36. The lowest scoring was found in the general health perception scale (GH), whereas role emotional (RE) and mental health (MH) were the scales least affected by hypertension. Nearly 20 percent of the antihypertensive drug users reported side effects.The pattern of side effects was similar to that reported in clinical trials. Both hypertension itself and the drug treatment were found to have an impact on the patient's health-state utility as measured by the RS. Comparative analyses showed that health utilities and psychometric quality-of-life instruments were only moderately correlated among hypertensives. The results also showed that inequalities in HRQL were present with respect to several sociodemographic factors. In summary, this thesis revealed that persons with cardiovascular disease and/or with hypertension experience poorer health than others in the population. The poor health may be caused both by the disease and/or the drug treatment. The results in this thesis also suggested that special attention and care should be directed to persons with cardiovascular disease and/or hypertension reporting ill health. This especially is important given that low HRQL can be a riskfactor for subsequent cardiovascular events or complications which in turn might result in higher mortality rate.