Heart Failure in Chronic Myocarditis: A Role for microRNAs?

Myocarditis is an inflammatory disease of the heart, which can persist over a long time. During this time, known as the chronic phase of myocarditis, ongoing inflammation damages the cardiomyocytes. The loss of cardiac cells culminates in the development of dilated cardiomyopathy, often followed by non-ischemic heart failure due to diminished cardiac function. During the course of the disease, expression levels of non-coding small RNAs, called microRNAs (miRNAs), change. Although mainly studied in the acute setting, some of these changes in expression level appear to persist in the chronic phase. In addition to being a much-needed diagnostic tool, these miRNA could provide new treatment options. miRNA-based intervention strategies already showed promising results in the treatment of ischemic cardiovascular diseases in preclinical animal models. By implementing more knowledge on the role of miRNAs in the progression towards heart failure, this can potentially be used in the development of miRNA-based therapeutic interventions in the treatment of myocarditis and thereby preventing the progression towards heart failure. The first part of this review will focus on the natural course of myocarditis and the progression towards heart failure. Secondly, we will discuss the current knowledge on alterations of miRNA expression patterns, and suggest some possible future interventions.

The relation between blood pressure and mortality due to coronary heart disease among men in different parts of the world. Seven Countries Study Research Group.

BACKGROUND: Elevated blood pressure is known to be a risk factor for death from coronary heart disease (CHD). However, it is unclear whether the risk of death from CHD in relation to blood pressure varies among populations. METHODS: In six populations in different parts of the world, we examined systolic and diastolic blood pressures and hypertension in relation to long-term mortality from CHD, both with and without adjustment for variability in blood pressure within individual subjects. Blood pressure was measured at base-line in 12,031 men (age range, 40 to 59 years) who were free of CHD. During 25 years of follow-up, 1291 men died from CHD. RESULTS: At systolic and diastolic blood pressures of about 140 and 85 mm Hg, respectively, 25-year rates of mortality from CHD (standardized for age) varied by a factor of more than three among the populations. Rates in the United States and northern Europe were high (approximately 70 deaths per 10,000 person-years), but rates in Japan and Mediterranean southern Europe were low (approximately 20 deaths per 10,000 person-years). However, the relative increase in 25-year mortality from CHD for a given increase in blood pressure was similar among the populations. The overall unadjusted relative risk of death due to CHD was 1.17 (95 percent confidence interval, 1.14 to 1.20) per 10 mm Hg increase in systolic pressure and 1.13 (95 percent confidence interval, 1.10 to 1.15) per 5 mm Hg increase in diastolic pressure, and it was 1.28 for each of these increments after adjustment for within-subject variability in blood pressure. CONCLUSIONS: Among the six populations we studied, the relative increase in long-term mortality due to CHD for a given increase in blood pressure is similar, whereas the absolute risk at the same level of blood pressure varies substantially. If the absolute risk of CHD is used as an indication for antihypertensive therapy, these findings will have major implications for treatment in different parts of the world.

Blood pressure and risk of myocardial infarction in elderly men and women: the Rotterdam study.

OBJECTIVE: To study the association between blood pressure and risk of myocardial infarction in elderly subjects. DESIGN: Prospective cohort study. SETTING: The Rotterdam Study, a Dutch population-based study. PARTICIPANTS: 6004 men and women aged > or = 55 years. MAIN OUTCOME MEASURES: Fatal or non-fatal myocardial infarction (n = 190) during a 4-year follow-up. RESULTS: After excluding participants using blood pressure-lowering medication and participants with a history of myocardial infarction, increasing levels of systolic blood pressure (SBP) were associated with increasing risk of first myocardial infarction (P for trend < 0.0001). The relative risk (RR) for an SBP of 160 mmHg or higher was 5.7 (95% confidence interval (CI) 1.9-17.1) compared with an SBP below 120 mmHg. Increasing diastolic blood pressure (DBP) was also associated with increasing risk of first myocardial infarction, with the RR reaching 2.5 (95% CI 1.4-4.5) in subjects with values of 80-90 mmHg compared with values below 70 mmHg (P for trend < 0.05). Analyses in subjects aged 70 years and over showed that the positive associations between SBP and DBP and risk of first myocardial infarction remained at older age. CONCLUSION: These findings in a relatively healthy cohort of elderly subjects do not provide evidence for a J- or U-shaped relation between SBP and DBP and risk of first myocardial infarction. They suggest that the risk of first myocardial infarction increases with increasing level of systolic and diastolic blood pressure and that this relationship persists into older age.

Height, weight weight change, and postmenopausal breast cancer risk: The Netherlands Cohort Study.

The association between several anthropometric indices and breast cancer risk was evaluated within the Netherlands Cohort Study on diet and cancer, which began in 1986 and is conducted among 62,573 women aged 55 to 69 years at baseline. After 4.3 years of follow-up, data on 626 women with incident breast cancer were available with complete information on height and weight at baseline. In multivariate case-cohort analyses, a significantly positive association between adult height and breast cancer was found (P trend < 0.001). Compared with women with height < or = 155 cm, the rate ratios of breast cancer for women with heights up to 160, 165, 170, 175, and > or = 175 cm were 1.22, 1.19, 1.44, 1.77, and 2.06, respectively. For weight at baseline, the significant positive association with breast cancer observed in age-adjusted analysis disappeared in multivariate analysis with adjustment for height and other confounders. For body mass index (BMI) (wt[kg]/ht[m]2) at baseline, no association was observed with breast cancer in multivariate analysis; compared with women with a BMI less than 23, the RR for women with a BMI of 30 or more was 0.98 with P trend = 0.46. Weight and BMI at age 20 showed weak inverse associations with breast cancer risk. For gain in weight or BMI between age 20 and cohort baseline age, inconsistent increases in risk were found, with no significant trends. These data support a positive association between height and breast cancer risk among postmenopausal women. Further study is needed to evaluate the role of early diet and breast cancer in this population, and its relationship to height.