Ella Zomer

The effectiveness and cost effectiveness of dark chocolate consumption as prevention therapy in people at high risk of cardiovascular disease: best case scenario analysis using a Markov model

Objective To model the long term effectiveness and cost effectiveness of daily dark chocolate consumption in a population with metabolic syndrome at high risk of cardiovascular disease. Design Best case scenario analysis using a Markov model. Setting Australian Diabetes, Obesity and Lifestyle study. Participants 2013 people with hypertension who met the criteria for metabolic syndrome, with no history of cardiovascular disease and not receiving antihypertensive therapy. Main outcome measures Treatment effects associated with dark chocolate consumption derived from published meta-analyses were used to determine the absolute number of cardiovascular events with and without treatment. Costs associated with cardiovascular events and treatments were applied to determine the potential amount of funding required for dark chocolate therapy to be considered cost effective. Results Daily consumption of dark chocolate (polyphenol content equivalent to 100 g of dark chocolate) can reduce cardiovascular events by 85 (95% confidence interval 60 to 105) per 10 000 population treated over 10 years.

Interventions that cause weight loss and the impact on cardiovascular risk factors: a systematic review and meta-analysis.

A40 (£25; €31;

Validation of two Framingham cardiovascular risk prediction algorithms in an Australian population: the ‘old’ versus the ‘new’ Framingham equation

42) could be cost effectively spent per person per year on prevention strategies using dark chocolate. These results assume 100% compliance and represent a best case scenario. Conclusions The blood pressure and cholesterol lowering effects of dark chocolate consumption are beneficial in the prevention of cardiovascular events in a population with metabolic syndrome. Daily dark chocolate consumption could be an effective cardiovascular preventive strategy in this population.

EFFECT OF UROTENSIN II ON SKIN MICROVESSEL TONE IN DIABETIC PATIENTS WITHOUT HEART FAILURE OR ESSENTIAL HYPERTENSION

Overweight and obesity increase the risks of diabetes and cardiovascular disease (CVD). This has been shown to be reversed with weight loss. A systematic review and meta‐analysis were performed to determine the effect of weight loss in the primary prevention of CVD. PubMed, Embase and the Cochrane Library databases were searched electronically through to May 2013. Randomized controlled trials assessing weight loss and cardiovascular risk factors and outcomes were included. A random effects meta‐analysis, with sub‐group analyses for degree of weight loss, and age were performed. Because few studies reported clinical outcomes of CVD, analyses were limited to cardiovascular risk factors (83 studies). Interventions that caused any weight loss significantly reduced systolic blood pressure (−2.68 mmHg, 95% CI −3.37, −2.11), diastolic blood pressure (−1.34 mmHg, 95% CI −1.71, −0.97), low‐density lipoprotein cholesterol (−0.20 mmol L−1, 95% CI −0.29, −0.10), triglycerides (−0.13 mmol L−1, 95% CI −0.22, −0.03), fasting plasma glucose (−0.32 mmol L−1, 95% CI −0.43, −0.22) and haemoglobin A1c(−0.40%, 95% CI −0.52, −0.28) over 6–12 months. Significant changes remained after 2 years for several risk factors. Similar results were seen in sub‐group analyses. Interventions that cause weight loss are effective at improving cardiovascular risk factors at least for 2 years.

Overview of pharmacoeconomic modelling methods

Background: Multivariable risk prediction equations attempt to quantify an individual’s cardiovascular risk. Those borne from the Framingham Heart Study remain the most well-established and widely used. In February 2008, a new Framingham risk equation was published. We sought to determine the differences between the most commonly used Framingham equation from 1991 and the 2008 version through their application to a contemporary Australian population. Methods and results: The two risk equations were applied to 7329 individuals from the Australian Diabetes, Obesity and Lifestyle study. All individuals were aged 30–74 years and free of cardiovascular disease. Differences in median risk scores were analyzed through the Wilcoxon’s signed rank test. Compared with the 1991 equation, median cardiovascular risk scores derived from the 2008 equation increased by 7 and 24% over 5 years, among males and females, respectively. The differences were statistically significant across all age-groups for both males and females, P value of less than 0.001. The performance of the equations in predicting cardiovascular outcomes were compared using event rates. The discriminative ability was increased using the 2008 equation; however the difference was non-significant [area under the receiver operating characteristic curve: 1991 equation 0.74 (0.69–0.80); 2008 equation 0.76 (0.71–0.81)]. Conclusion: Earlier Framingham equations have been suggested to over-predict cardiovascular risk in low-risk populations and under-predict risk in high-risk groups. This is the first comparative validation of the previous 1991 and most recent 2008 equations. This study highlights the need to validate and calibrate cardiovascular risk prediction equations using the population-specific outcome data.

Cardiovascular risk prediction in a population with the metabolic syndrome: Framingham vs. UKPDS algorithms

1 Urotensin II (UII) is a potent vasoconstrictor peptide. Increased plasma levels and kidney expression of UII and its receptor have been observed in diabetes mellitus (DM). The aim of the present study was to evaluate the direct effect of exogenous UII on microvascular tone in DM patients compared with healthy controls. 2 Vasoactive effect of UII (10−12, 10−9 and 10−7 mol/L) on skin microvascular tone was evaluated in 12 controls and 12 DM patients (Type 1 or Type 2) without concomitant heart failure or essential hypertension using the non‐invasive technique of iontophoresis and laser Doppler velocimetry. In addition, responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were evaluated. 3 Urotensin II dose‐dependently dilated skin microvasculature in control subjects (–51.8 ± 59.4, 138.6 ± 101.5, 204.2 ± 115.7 and 207.5 ± 81.6 arbitrary flux units (AFUs) for MilliQ and 10−12, 10−9 and 10−7 mol/L UII, respectively) and dose‐dependently vasoconstricted the microvasculature in DM patients (100.8 ± 81.2, 46.2 ± 85.1, 35.4 ± 81.4 and 26.6 ± 79.6 AFUs for MilliQ and 10−12, 10−9 and 10−7 mol/L UII, respectively). Blood flow in control subjects and DM patients was differed significantly, with pair‐wise comparisons indicating differences for 10−9 and 10−7 mol/L UII (P = 0.04 and P = 0.003). Results of blood flow in diet‐controlled DM patients (204.7 ± 193.6, 261.2 ± 212.8, 256.1 ± 202.9 and 233.7 ± 115.9 AFUs for MilliQ and 10−12, 10−9 and 10−7 mol/L UII, respectively) were similar to those in control subjects compared with results for DM patients receiving antidiabetic medication (48.8 + 80.0, –61.4 ± 49.1, –75.0 ± 40.0, –91.7 ± 80.0 AFUs for MilliQ and 10−12, 10−9 and 10−7 mol/L UII, respectively). Between‐group significance remained after adjustment for baseline blood pressure values. 4 Acetylcholine vasodilator responses were attenuated in DM patients compared with those in control subjects (1309.5 ± 488.6 vs 3498.0 ± 912.5 AFUs, respectively), whereas SNP responses were similar in the two groups (1467.9 ± 411.3 vs 1984.4 ± 410.7 AFUs, respectively). 5 In conclusion, UII causes net vasoconstriction in DM. The UII‐induced increases in peripheral vascular tone may contribute to DM‐related cardiovascular complications.

Urotensin II in chronic liver disease: in vivo effect on vascular tone.

In the current climate of burgeoning health care costs, pharmacoeconomics is becoming increasingly important, but knowledge about pharmacoeconomic methods is limited among most clinicians. This review provides an introduction to, and overview of, common methods used in pharmacoeconomic modelling: decision analysis, Markov modelling, discounting and uncertainty analyses via Monte Carlo simulation. It will conclude with a suggested approach to reading and appraising published pharmacoeconomic analyses.

Adherence and Persistence among Statin Users Aged 65 Years and Over: A Systematic Review and Meta-analysis

Background: Cardiovascular disease (CVD) risk-prediction algorithms are key in determining one’s eligibility for prevention strategies, but are often population-specific. Metabolic syndrome (MetS), a clustering of risk factors that increase the risk of CVD, does not currently have a risk-prediction algorithm available for prediction of CVD. The aim of this study was to compare the predictive capacities of an algorithm intended for ‘healthy’ individuals and one intended for ‘diabetic’ individuals. Methods: Individual-specific data from 2700 subjects defined as MetS but free of diagnosed CVD from the Australian Diabetes, Obesity and Lifestyle study was used to estimate 5-year risk of CVD using the two algorithms, and compared using Wilcoxon-signed rank test. CVD end point data was used to assess the performance using discrimination and calibration techniques of the two algorithms. Results: Five-year risk-prediction comparisons demonstrated that the UKPDS algorithm overpredicted risk in the younger age groups (25–54 years) and underpredicted risk in the older age groups (≥55 years) compared to the Framingham algorithm. A total of 133 CVD events occurred over a median follow up of 5.0 years. Model performance analyses demonstrated both the Framingham and UKPDS algorithms were poor at discrimination (area under receiver operator curve 0.513 and 0.524, respectively) and calibration (Hosmer-Lemeshow 467.1 and 297.0, respectively). Conclusions: Neither the Framingham or UKPDS algorithms are ideal for prediction of CVD risk in a MetS population. This study highlights the need for development of population-specific risk-prediction algorithms for this growing population group.

Patterns and Predictors of Adherence to Statin Therapy Among Older Patients: Protocol for a Systematic Review

Objective. Urotensin II (UII) is now recognized as the most potent human vasoconstrictor. Although its role in human pathophysiology is unknown, vasoactive mediators are known to be important in the pathogenesis of portal hypertension complicating chronic liver disease. The objective of this study was to investigate the role of UII in liver cirrhosis via examination of the in vivo effect of UII in this patient group. Material and methods. The vasoactive effects of UII were measured using Laser Doppler velocimetry on cirrhotic patients (n=14) and age-matched healthy controls (n=14) after UII administration by iontophoresis to the cutaneous microcirculation of the forearm. Results. In vivo administration of UII produced vasoconstriction of the cutaneous microcirculation in the cirrhotic group and vasodilatation in the controls, with values differing significantly at the two highest doses of UII: 10−9 mol (p=0.01) and 10−7 mol (p=0.004). Conclusions. UII mediates vasoconstriction of the microcirculation of cirrhotics but not of controls. This suggests that UII has pathophysiological relevance in the portal hypertensive population through its vasoactive properties. Further studies of UII and UII-antagonists are warranted in this patient population.

Effectiveness and cost-effectiveness of interventions that cause weight loss and reduce the risk of cardiovascular disease

Background Older people (aged ≥ 65 years) have distinctive challenges with medication adherence. However, adherence and persistence patterns among older statin users have not been comprehensively reviewed. Methods As part of a broader systematic review, we searched Medline, Embase, PsycINFO, CINAHL, Database of Abstracts of Reviews of Effects, CENTRAL, and the National Health Service Economic Evaluation Database through December 2016 for English articles reporting adherence and/or persistence among older statin users. Data were analyzed via descriptive methods and meta-analysis using random-effect modeling. Results Data from more than 3 million older statin users in 82 studies conducted in over 40 countries were analyzed. At 1-year follow-up, 59.7% (primary prevention 47.9%; secondary prevention 62.3%) of users were adherent (medication possession ratio [MPR] or proportion of days covered [PDC] ≥ 80%). For both primary and secondary prevention subjects, 1-year adherence was worse among individuals aged more than 75 years than those aged 65-75 years. At 3 and ≥10 years, 55.3% and 28.4% of users were adherent, respectively. The proportion of users persistent at 1-year was 76.7% (primary prevention 76.0%; secondary prevention 82.6%). Additionally, 68.1% and 61.2% of users were persistent at 2 and 4 years, respectively. Among new statin users, 48.2% were nonadherent and 23.9% discontinued within the first year. The proportion of statin users who were adherent based on self-report was 85.5%. Conclusions There is poor short and long term adherence and persistence among older statin users. Strategies to improve adherence and reduce discontinuation are needed if the intended cardiovascular benefits of statin treatment are to be realized.