Effects on blood pressure and cardiovascular risk of variations in patients' adherence to prescribed antihypertensive drugs: role of duration of drug action.

P>Aim: To determine the effects of imperfect adherence (i.e. occasionally missing prescribed doses), and the influence of rate of loss of antihypertensive effect during treatment interruption, on the predicted clinical effectiveness of antihypertensive drugs in reducing mean systolic blood pressure (SBP) and cardiovascular disease (CVD) risk.Method:The effects of imperfect adherence to antihypertensive treatment regimens were estimated using published patterns of missed doses, and taking into account the rate of loss of antihypertensive effect when doses are missed (loss of BP reduction in mmHg/day; the off-rate), which varies between drugs. Outcome measures were the predicted mean SBP reduction and CVD risk, determined from the Framingham Risk Equation for CVD.Results:In patients taking 75% of prescribed doses (typical of clinical practice), only long-acting drugs with an off-rate of similar to 1 mmHg/day were predicted to maintain almost the full mean SBP-lowering effect throughout the modelled period. In such patients, using shorter-acting drugs (e.g. an off-rate of similar to 5-6 mmHg/day) was predicted to lead to a clinically relevant loss of mean SBP reduction of > 2 mmHg. This change also influenced the predicted CVD risk reduction; in patients with a baseline 10-year CVD risk of 27.0% and who were taking 75% of prescribed doses, a difference in off-rate from 1 to 5 mmHg/day led to a predicted 0.5% absolute increase in 10-year CVD risk.Conclusions:In patients who occasionally miss doses of antihypertensives, modest differences in the rate of loss of antihypertensive effect following treatment interruption may have a clinically relevant impact on SBP reduction and CVD risk. While clinicians must make every effort to counsel and encourage each of their patients to adhere to their prescribed medication, it may also be prudent to prescribe drugs with a low off-rate to mitigate the potential consequences of missing doses.

Subclinical thyroid dysfunction, cardiac function, and the risk of heart failure. The Cardiovascular Health study.

OBJECTIVES: The goal of this study was to determine whether subclinical thyroid dysfunction was associated with incident heart failure (HF) and echocardiogram abnormalities. BACKGROUND: Subclinical hypothyroidism and hyperthyroidism have been associated with cardiac dysfunction. However, long-term data on the risk of HF are limited. METHODS: We studied 3,044 adults>or=65 years of age who initially were free of HF in the Cardiovascular Health Study. We compared adjudicated HF events over a mean 12-year follow-up and changes in cardiac function over the course of 5 years among euthyroid participants, those with subclinical hypothyroidism (subdivided by thyroid-stimulating hormone [TSH] levels: 4.5 to 9.9, >or=10.0 mU/l), and those with subclinical hyperthyroidism. RESULTS: Over the course of 12 years, 736 participants developed HF events. Participants with TSH>or=10.0 mU/l had a greater incidence of HF compared with euthyroid participants (41.7 vs. 22.9 per 1,000 person years, p=0.01; adjusted hazard ratio: 1.88; 95% confidence interval: 1.05 to 3.34). Baseline peak E velocity, which is an echocardiographic measurement of diastolic function associated with incident HF in the CHS cohort, was greater in those patients with TSH>or=10.0 mU/l compared with euthyroid participants (0.80 m/s vs. 0.72 m/s, p=0.002). Over the course of 5 years, left ventricular mass increased among those with TSH>or=10.0 mU/l, but other echocardiographic measurements were unchanged. Those patients with TSH 4.5 to 9.9 mU/l or with subclinical hyperthyroidism had no increase in risk of HF. CONCLUSIONS: Compared with euthyroid older adults, those adults with TSH>or=10.0 mU/l have a moderately increased risk of HF and alterations in cardiac function but not older adults with TSH<10.0 mU/l. Clinical trials should assess whether the risk of HF might be ameliorated by thyroxine replacement in individuals with TSH>or=10.0 mU/l.

Accuracy of four cardiovascular risk scores in a Swiss population-based cohort

Purpose: To assess the global cardiovascular (CV) risk of an individual, several scores have been developed. However, their accuracy and comparability need to be evaluated in populations others from which they were derived. The aim of this study was to compare the predictive accuracy of 4 CV risk scores using data of a large population-based cohort. Methods: Prospective cohort study including 4980 participants (2698 women, mean age± SD: 52.7±10.8 years) in Lausanne, Switzerland followed for an average of 5.5 years (range 0.2 - 8.5). Two end points were assessed: 1) coronary heart disease (CHD), and 2) CV diseases (CVD). Four risk scores were compared: original and recalibrated Framingham coronary heart disease scores (1998 and 2001); original PROCAM score (2002) and its recalibrated version for Switzerland (IAS-AGLA); Reynolds risk score. Discrimination was assessed using Harrell's C statistics, model fitness using Akaike's information criterion (AIC) and calibration using pseudo Hosmer-Lemeshow test. The sensitivity, specificity and corresponding 95% confidence intervals were assessed for each risk score using the highest risk category ([20+ % at 10 years) as the "positive" test. Results: Recalibrated and original 1998 and original 2001 Framingham scores show better discrimination (>0.720) and model fitness (low AIC) for CHD and CVD. All 4 scores are correctly calibrated (Chi2<20). The recalibrated Framingham 1998 score has the best sensitivities, 37.8% and 40.4%, for CHD and CVD, respectively. All scores present specificities >90%. Framingham 1998, PROCAM and IAS-AGLA scores include the greatest proportion of subjects (>200) in the high risk category whereas recalibrated Framingham 2001 and Reynolds include <=44 subjects. Conclusion: In this cohort, we see variations of accuracy between risk scores, the original Framingham 2001 score demonstrating the best compromise between its accuracy and its limited selection of subjects in the highest risk category. We advocate that national guidelines, based on independently validated data, take into account calibrated CV risk scores for their respective countries.

Angiotensin II-mediated adaptive and maladaptive remodeling of cardiomyocyte excitation-contraction coupling.

Cardiac hypertrophy is associated with alterations in cardiomyocyte excitation-contraction coupling (ECC) and Ca(2+) handling. Chronic elevation of plasma angiotensin II (Ang II) is a major determinant in the pathogenesis of cardiac hypertrophy and congestive heart failure. However, the molecular mechanisms by which the direct actions of Ang II on cardiomyocytes contribute to ECC remodeling are not precisely known. This question was addressed using cardiac myocytes isolated from transgenic (TG1306/1R [TG]) mice exhibiting cardiac specific overexpression of angiotensinogen, which develop Ang II-mediated cardiac hypertrophy in the absence of hemodynamic overload. Electrophysiological techniques, photolysis of caged Ca(2+) and confocal Ca(2+) imaging were used to examine ECC remodeling at early ( approximately 20 weeks of age) and late ( approximately 60 weeks of age) time points during the development of cardiac dysfunction. In young TG mice, increased cardiac Ang II levels induced a hypertrophic response in cardiomyocyte, which was accompanied by an adaptive change of Ca(2+) signaling, specifically an upregulation of the Na(+)/Ca(2+) exchanger-mediated Ca(2+) transport. In contrast, maladaptation was evident in older TG mice, as suggested by reduced sarcoplasmic reticulum Ca(2+) content resulting from a shift in the ratio of plasmalemmal Ca(2+) removal and sarcoplasmic reticulum Ca(2+) uptake. This was associated with a conserved ECC gain, consistent with a state of hypersensitivity in Ca(2+)-induced Ca(2+) release. Together, our data suggest that chronic elevation of cardiac Ang II levels significantly alters cardiomyocyte ECC in the long term, and thereby contractility, independently of hemodynamic overload and arterial hypertension.

Comparative cardiovascular effects of drugs used for hypertension.

Currently 4 classes of antihypertensive drugs - diuretics, beta-blockers, calcium channel blockers and angiotensin-converting enzyme (ACE) inhibitors - are most commonly used to treat hypertensive patients. Each class of drug has a distinctive cardiovascular pharmacodynamic profile and even within classes there exist agents with slightly different properties. The effects of the various drug classes on the heart and peripheral circulation, on the kidney and electrolyte metabolism, on the brain and on the renin-angiotensin system are now reasonably well described. Knowledge and understanding of these different cardiovascular effects are extremely important in order to adapt treatment to the needs of an individual patient. Furthermore, when combination therapy becomes necessary, the different cardiovascular aspects of the various drugs can be used to enhance antihypertensive efficacy and to attenuate adverse effects of separate compounds.

Assessment of cardiac ischaemia and viability: role of cardiovascular magnetic resonance.

Over the past years, cardiovascular magnetic resonance (CMR) has proven its efficacy in large clinical trials, and consequently, the assessment of function, viability, and ischaemia by CMR is now an integrated part of the diagnostic armamentarium in cardiology. By combining these CMR applications, coronary artery disease (CAD) can be detected in its early stages and this allows for interventions with the goal to reduce complications of CAD such as infarcts and subsequently chronic heart failure (CHF). As the CMR examinations are robust and reproducible and do not expose patients to radiation, they are ideally suited for repetitive studies without harm to the patients. Since CAD is a chronic disease, the option to monitor CAD regularly by CMR over many decades is highly valuable. Cardiovascular magnetic resonance also progressed recently in the setting of acute coronary syndromes. In this situation, CMR allows for important differential diagnoses. Cardiovascular magnetic resonance also delineates precisely the different tissue components in acute myocardial infarction such as necrosis, microvascular obstruction (MVO), haemorrhage, and oedema, i.e. area at risk. With these features, CMR might also become the preferred tool to investigate novel treatment strategies in clinical research. Finally, in CHF patients, the versatility of CMR to assess function, flow, perfusion, and viability and to characterize tissue is helpful to narrow the differential diagnosis and to monitor treatment.

Improvement of cardiovascular risk prediction: time to review current knowledge, debates, and fundamentals on how to assess test characteristics.

Cardiovascular risk assessment might be improved with the addition of emerging, new tests derived from atherosclerosis imaging, laboratory tests or functional tests. This article reviews relative risk, odds ratios, receiver-operating curves, posttest risk calculations based on likelihood ratios, the net reclassification improvement and integrated discrimination. This serves to determine whether a new test has an added clinical value on top of conventional risk testing and how this can be verified statistically. Two clinically meaningful examples serve to illustrate novel approaches. This work serves as a review and basic work for the development of new guidelines on cardiovascular risk prediction, taking into account emerging tests, to be proposed by members of the 'Taskforce on Vascular Risk Prediction' under the auspices of the Working Group 'Swiss Atherosclerosis' of the Swiss Society of Cardiology in the future.

A two-week workshop to promote cardiovascular disease prevention programs in countries with limited resources.

Training is a crucial tool for building the capacity necessary for prevention and control of cardiovascular diseases (CVDs) in developing countries. This paper summarizes some features of a 2-week workshop aimed at enabling local health professionals to initiate a comprehensive CVD prevention and control program in a context of limited resources. The workshops have been organized in the regions where CVD prevention programs are being contemplated, in cooperation with health authorities of the concerned regions. The workshop's content includes a broad variety of issues related to CVD prevention and control, and to program development. Strong emphasis is placed on "learning by doing," and groups of 5-6 participants conduct a small-scale epidemiological study during the first week; during the second week, they draft a virtual program of CVD prevention and control adapted to the local situation. This practice-oriented workshop focuses on building expertise among anticipated key players, strengthening networks among relevant health professionals, and advocating the urgent need to tackle the emerging CVD epidemic in developing countries.

Cardiovascular effects in patrol officers are associated with fine particulate matter from brake wear and engine emissions

Background: Exposure to fine particulate matter air pollutants (PM2.5) affects heart rate variability parameters, and levels of serum proteins associated with inflammation, hemostasis and thrombosis. This study investigated sources potentially responsible for cardiovascular and hematological effects in highway patrol troopers. Results: Nine healthy young non-smoking male troopers working from 3 PM to midnight were studied on four consecutive days during their shift and the following night. Sources of in-vehicle PM2.5 were identified with variance-maximizing rotational principal factor analysis of PM2.5-components and associated pollutants. Two source models were calculated. Sources of in-vehicle PM2.5 identified were 1) crustal material, 2) wear of steel automotive components, 3) gasoline combustion, 4) speed-changing traffic with engine emissions and brake wear. In one model, sources 1 and 2 collapsed to a single source. Source factors scores were compared to cardiac and blood parameters measured ten and fifteen hours, respectively, after each shift. The "speed-change" factor was significantly associated with mean heart cycle length (MCL, +7% per standard deviation increase in the factor score), heart rate variability (+16%), supraventricular ectopic beats (+39%), % neutrophils (+7%), % lymphocytes (-10%), red blood cell volume MCV (+1%), von Willebrand Factor (+9%), blood urea nitrogen (+7%), and protein C (-11%). The "crustal" factor (but not the "collapsed" source) was associated with MCL (+3%) and serum uric acid concentrations (+5%). Controlling for potential confounders had little influence on the effect estimates. Conclusion: PM2.5 originating from speed-changing traffic modulates the autonomic control of the heart rhythm, increases the frequency of premature supraventricular beats and elicits proinflammatory and pro-thrombotic responses in healthy young men. [Authors]

Assessing the associations between mental disorders, cardiovascular risk factors, and cardiovascular disease : the CoLaus/PsyCoLaus study

Background: Cardio-vascular diseases (CVD), their well established risk factors (CVRF) and mental disorders are common and co-occur more frequently than would be expected by chance. However, the pathogenic mechanisms and course determinants of both CVD and mental disorders have only been partially identified.Methods/Design: Comprehensive follow-up of CVRF and CVD with a psychiatric exam in all subjects who participated in the baseline cross-sectional CoLaus study (2003-2006) (n=6'738) which also included a comprehensive genetic assessment. The somatic investigation will include a shortened questionnaire on CVRF, CV events and new CVD since baseline and measurements of the same clinical and biological variables as at baseline. In addition, pro-inflammatory markers, persistent pain and sleep patterns and disorders will be assessed. In the case of a new CV event, detailed information will be abstracted from medical records. Similarly, data on the cause of death will be collected from the Swiss National Death Registry. The comprehensive psychiatric investigation of the CoLaus/PsyCoLaus study will use contemporary epidemiological methods including semi-structured diagnostic interviews, experienced clinical interviewers, standardized diagnostic criteria including threshold according to DSM-IV and sub-threshold syndromes and supplementary information on risk and protective factors for disorders. In addition, screening for objective cognitive impairment will be performed in participants older than 65 years.Discussion: The combined CoLaus/PsyCoLaus sample provides a unique opportunity to obtain prospective data on the interplay between CVRF/CVD and mental disorders, overcoming limitations of previous research by bringing together a comprehensive investigation of both CVRF and mental disorders as well as a large number of biological variables and a genome-wide genetic assessment in participants recruited from the general population.