Sina Kianoush

The Role of mHealth for Improving Medication Adherence in Patients with Cardiovascular Disease: A Systematic Review

Cardiovascular disease is a leading cause of morbidity and mortality worldwide, and a key barrier to improved outcomes is medication non-adherence. The aim of this study is to review the role of mobile health (mHealth) tools for improving medication adherence in patients with cardiovascular disease. We performed a systematic search for randomized controlled trials that primarily investigated mHealth tools for improving adherence to cardiovascular disease medications in patients with hypertension, coronary artery disease, heart failure, peripheral arterial disease, and stroke. We extracted and reviewed data on the types of mHealth tools used, preferences of patients and healthcare providers, the effect of the mHealth interventions on medication adherence, and the limitations of trials. We identified 10 completed trials matching our selection criteria, mostly with <100 participants, and ranging in duration from 1 to 18 months. mHealth tools included text messages, Bluetooth-enabled electronic pill boxes, online messaging platforms, and interactive voice calls. Patients and healthcare providers generally preferred mHealth to other interventions. All 10 studies reported that mHealth interventions improved medication adherence, though the magnitude of benefit was not consistently large and in one study was not greater than a telehealth comparator. Limitations of trials included small sample sizes, short duration of follow-up, self-reported outcomes, and insufficient assessment of unintended harms and financial implications. Current evidence suggests that mHealth tools can improve medication adherence in patients with cardiovascular diseases. However, high-quality clinical trials of sufficient size and duration are needed to move the field forward and justify use in routine care.

Risk of Stent Thrombosis and Major Bleeding with Bivalirudin Compared with Active Control: A Systematic Review and Meta-analysis of Randomized Trials

BACKGROUND Bivalirudin is commonly used for patients undergoing percutaneous coronary intervention (PCI), but there have been recent concerns that it may be associated with an increased risk of stent thrombosis and provide no benefit regarding major bleeding compared with active control. METHODS AND RESULTS We searched PubMed, clinicaltrials.gov, and conference proceedings for randomized controlled trials of bivalirudin versus active control in patients undergoing PCI. The main outcomes of interest were definite stent thrombosis, myocardial infarction, major bleeding, and mortality. We used random-effects modeling to pool the data. We included 25 trials involving 41,243 patients. Overall, use of bivalirudin compared with active control was associated with an increased risk of definite stent thrombosis (11 trials; 16,864 patients; RR, 1.73; 95% CI, 1.24-2.40; P<0.001; I(2)=0%), similar risk of acute myocardial infarction (22 trials; 40,578 patients; RR, 1.00; 95% CI, 0.87-1.16; P=0.96; I(2)=43%), decreased risk of major bleeding (25 trials; 41,243 patients; RR, 0.59; 95% CI, 0.49-0.72; P<0.001; I(2)=31%) and of cardiac death (6 trials; 6,956 patients; RR, 0.72; 95% CI, 0.53-0.99; P=0.05; I(2)=0%), but no change in all-cause mortality (24 trials; 41,058 patients; RR, 0.96; 95% CI, 0.81-1.15; P=0.69; I(2)=0%). Results were consistent across a wide set of subgroup and sensitivity analyses. CONCLUSIONS Compared with active control, bivalirudin is associated with increased risk of stent thrombosis but lower risk of major bleeding, with no discernible impact on all-cause mortality.

Comparison of Therapeutic Effects of Garlic and d-Penicillamine in Patients with Chronic Occupational Lead Poisoning

Previous studies on animals have revealed that garlic (Allium sativum) is effective in reducing blood and tissue lead concentrations. The aim of this study was to investigate therapeutic effects of garlic and compare it with d-penicillamine in patients with chronic lead poisoning. After coordination and obtaining informed consent, clinical examinations and blood lead concentration (BLC) of 117 workers at a car battery industry were investigated. BLC was determined by heated graphite atomization technique of an atomic absorption spectrometer. The workers were randomly assigned into two groups of garlic (1200 μg allicin, three times daily) and d-penicillamine (250 mg, three times daily) and treated for 4 weeks. BLC was determined again 10days post-treatment. Clinical signs and symptoms of lead poisoning were also investigated and compared with the initial findings. Clinical improvement was significant in a number of clinical manifestations including irritability (p = 0.031), headache (p = 0.028), decreased deep tendon reflex (p=0.019) and mean systolic blood pressure (0.021) after treatment with garlic, but not d-penicillamine. BLCs were reduced significantly (p=0.002 and p=0.025) from 426.32±185.128 to 347.34±121.056 μg/L and from 417.47±192.54 to 315.76±140.00μg/L in the garlic and d-penicillamine groups, respectively, with no significant difference (p=0.892) between the two groups. The frequency of side effects was significantly (p=0.023) higher in d-penicillamine than in the garlic group. Thus, garlic seems safer clinically and as effective as d-penicillamine. Therefore, garlic can be recommended for the treatment of mild-to-moderate lead poisoning.

Comparative study of topical application of timolol and verapamil in patients with glaucoma within 6 months.

INTRODUCTION As glaucoma is one of the most significant causes of blindness, and administration of calcium channel blockers is effective in reducing intraocular pressure (IOP) in rabbits and patients with normotensive glaucoma, we administered topical verapamil 0.25% in the human eye to compare its effect with timolol 0.5% in reducing IOP. PURPOSE To compare the effect of timolol 0.5% and topical verapamil 0.25% in patients with open-angle glaucoma. METHODS It was a double-blinded study in which 118 eyes (59 individuals) were chosen and divided into 2 groups (30 individuals related to timolol and 29 individuals related to verapamil). Patients who used drugs (systemic or topical) that could alter IOP and those with IOP <22 mmHg were excluded from the study (19 eyes). We chose patients who did not use any drugs 24 h prior to the study. Then applanation tonometry was done exactly before the administration of drugs and 90 min later and the results were compared. RESULTS In timolol group, mean intraocular pressure in 52 eyes (27 right eyes and 25 left eyes) decreased from 32.545 to 30.230 and mean pressure in verapamil group decreased from 33.195 to 30.835. CONCLUSION It seems that topical verapamil has a similar effect to timolol in patients with open-angle glaucoma, so it can be considered as a lowering intraocular pressure agent in glaucoma patients.

An Update on the Utility of Coronary Artery Calcium Scoring for Coronary Heart Disease and Cardiovascular Disease Risk Prediction

Estimating cardiovascular disease (CVD) risk is necessary for determining the potential net benefit of primary prevention pharmacotherapy. Risk estimation relying exclusively on traditional CVD risk factors may misclassify risk, resulting in both undertreatment and overtreatment. Coronary artery calcium (CAC) scoring personalizes risk prediction through direct visualization of calcified coronary atherosclerotic plaques and provides improved accuracy for coronary heart disease (CHD) or CVD risk estimation. In this review, we discuss the most recent studies on CAC, which unlike historical studies, focus sharply on clinical application. We describe the MESA CHD risk calculator, a recently developed CAC-based 10-year CHD risk estimator, which can help guide preventive therapy allocation by better identifying both high- and low-risk individuals. In closing, we discuss calcium density, regional distribution of CAC, and extra-coronary calcification, which represent the future of CAC and CVD risk assessment research and may lead to further improvements in risk prediction.

Associations of Cigarette Smoking With Subclinical Inflammation and Atherosclerosis: ELSA-Brasil (The Brazilian Longitudinal Study of Adult Health)

Background There is a need to identify sensitive biomarkers of early tobacco‐related cardiovascular disease. We examined the association of smoking status, burden, time since quitting, and intensity, with markers of inflammation and subclinical atherosclerosis. Methods and Results We studied 14 103 participants without clinical cardiovascular disease in ELSA‐Brasil (Brazilian Longitudinal Study of Adult Health). We evaluated baseline cross‐sectional associations between smoking parameters and inflammation (high‐sensitivity C‐reactive protein [hsCRP]) and measures of subclinical atherosclerosis (carotid intima–media thickness, ankle‐brachial index, and coronary artery calcium [CAC]). The cohort included 1844 current smokers, 4121 former smokers, and 8138 never smokers. Mean age was 51.7±8.9 years; 44.8% were male. After multivariable adjustment, compared with never smokers, current smokers had significantly higher levels of hsCRP (β=0.24, 0.19–0.29 mg/L; P<0.001) and carotid intima–media thickness (β=0.03, 0.02–0.04 mm; P<0.001) and odds of ankle‐brachial index ≤1.0 (odds ratio: 2.52; 95% confidence interval, 2.06–3.08; P<0.001) and CAC >0 (odds ratio: 1.83; 95% confidence interval, 1.46–2.30; P<0.001). Among former and current smokers, pack‐years of smoking (burden) were significantly associated with hsCRP (P<0.001 and P=0.006, respectively) and CAC (P<0.001 and P=0.002, respectively). Among former smokers, hsCRP and carotid intima–media thickness levels and odds of ankle‐brachial index ≤1.0 and CAC >0 were lower with increasing time since quitting (P<0.01). Among current smokers, number of cigarettes per day (intensity) was positively associated with hsCRP (P<0.001) and CAC >0 (P=0.03) after adjusting for duration of smoking. Conclusions Strong associations were observed between smoking status, burden, and intensity with inflammation (hsCRP) and subclinical atherosclerosis (carotid intima–media thickness, ankle‐brachial index, CAC). These markers of early cardiovascular disease injury may be used for the further study and regulation of traditional and novel tobacco products.

The association between cigarette smoking and inflammation: The Genetic Epidemiology Network of Arteriopathy (GENOA) study

To inform the study and regulation of emerging tobacco products, we sought to identify sensitive biomarkers of tobacco-induced subclinical cardiovascular damage by testing the cross-sectional associations of smoking with 17 biomarkers of inflammation in 2,702 GENOA study participants belonging to sibships ascertained on the basis of hypertension. Cigarette smoking was assessed by status, intensity (number of cigarettes per day), burden (pack-years of smoking), and time since quitting. We modeled biomarkers as geometric mean (GM) ratios using generalized estimating equations (GEE). The mean age of participants was 61 ±10 years; 64.5% were women and 54.4% African American. The prevalence of smoking was 12.2%. After adjusting for potential confounders, 6 of 17 biomarkers were significantly higher among current smokers at a Bonferroni adjusted p-value threshold (p<0.003). High sensitivity C-reactive protein was the most elevated biomarker among current smokers when compared to never smokers [GM ratio = 1.39 (95% CI: 1.23, 1.57); p <0.001]. Among former smokers, each pack-year of cigarettes smoked was associated with a 0.4% higher serum level of hsCRP [GM ratio = 1.004 (95% CI: 1.001, 1.006); p = 0.002] and each 5-year lapsed since quitting was associated with a 4% lower serum level of hsCRP [GM ratio = 0.96 (95% CI: 0.93, 0.99); p = 0.006]. However, we found no significant association of smoking intensity or burden with biomarkers of inflammation among current smokers. HsCRP appears to be the most sensitive biomarker of inflammation associated with cigarette smoking of those investigated, and could be a useful biomarker of smoking-related injury for the study and regulation of emerging tobacco products.

Stratifying cardiovascular risk in diabetes: The role of diabetes-related clinical characteristics and imaging

Diabetes is a major coronary heart disease (CHD) and cardiovascular disease (CVD) risk factor and has traditionally been classified as a CHD risk equivalent. CVD risk, however, is heterogeneous among diabetic patients and thus further evaluation is warranted before initiating or titrating preventive pharmacotherapy. Prognostic clinical characteristics of diabetes such as age of onset, duration, and severity of diabetes, as well as concomitant cardiometabolic factors account for much of the variability in CHD and CVD risk. This heterogeneity can also be evaluated directly using non-invasive imaging, which allows for a more individualized risk assessment in order to minimize both under and overtreatment. In this paper, we review guideline recommendations for atherosclerotic CVD risk assessment driving the use of statins or aspirin for certain subgroups of patients with diabetes. We further discuss imaging techniques, such as stress myocardial perfusion imaging, coronary computed tomography angiography, and coronary artery calcium (CAC) scoring that can guide the decision to treat high-risk patients. Among imaging tests, current guidelines consider CAC scoring the most appropriate risk stratification tool for asymptomatic individuals with diabetes that can guide initiating/intensifying or withholding the most aggressive pharmacological therapies among high-risk (CAC>100) or low-risk (CAC=0) individuals, respectively.

Coronary Artery Calcium Scoring in Current Clinical Practice: How to Define Its Value?

Opinion statementDetecting subclinical atherosclerosis with coronary artery calcium (CAC) is promising for identifying individuals at risk for cardiovascular events and appears to be a robust tool for guiding initiation of appropriate and timely primary prevention strategies. However, how do we best determine its clinical value? It is clear that traditional risk prediction models based primarily on age, gender, and risk factors are insufficient for ideal personalization of risk estimation. It is now well established from epidemiologic studies that CAC adds to traditional risk scores for a more accurate risk prediction. However, such traditional epidemiology studies have limitations in establishing “clinical value,” and they must be supplemented by additional data before being translated into strong recommendations in clinical practice guidelines. Fortunately, over the last few years, the research around CAC has matured to include data supporting enhanced clinician-patient risk discussions, shared decision-making, flexible risk factor treatment goals, specific clinical decision algorithms, as well as favorable cost-effectiveness analyses. We had moved from a time when we asked “if CAC adds to the risk score” to a time when we are asking “does CAC facilitate a shared decision-making model matching risk, treatment, and patient preferences?” A new risk calculator incorporating CAC into global risk scoring, and 2017 guidelines on the use of CAC published by the Society of Cardiovascular Computed Tomography (SCCT), reflect this new approach. In this article, we review the recent transition to this more clinically relevant CAC research that may support a stronger recommendation for its use in future prevention guidelines.

Statin Eligibility, Coronary Artery Calcium, and Subsequent Cardiovascular Events According to the 2016 United States Preventive Services Task Force (USPSTF) Statin Guidelines: MESA (Multi‐Ethnic Study of Atherosclerosis)

Background The potential impact of the 2016 United States Preventive Services Task Force (USPSTF) guidelines on statins for primary prevention of atherosclerotic cardiovascular disease (ASCVD) warrants further analysis. Methods and Results We studied participants from MESA (Multi‐Ethnic Study of Atherosclerosis) aged 40 to 75 years and not on statins. We compared statin eligibility at baseline (2000–2002) and over follow‐up between USPSTF and the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines. Coronary artery calcium (CAC) was measured at baseline. Absolute ASCVD event rates were calculated according to eligibility categories for each guideline. Among 4962 MESA participants (aged 59.3±8.8 years, 47.2% female), compared with ACC/AHA guidelines, baseline statin eligibility by USPSTF was significantly lower (34.4% versus 49.1%) and increased less over time (39.1% versus 59.1%) at examination 5 [years 2010–2012]). Compared with ACC/AHA, participants eligible by USPSTF were less likely to have zero CAC at baseline (36.6% versus 41.2%) and had higher rates of hard ASCVD events per 1000 person‐years (11.6 [95% confidence interval, 10.2–13.3] versus 10.0 [8.9–11.3]). The hard ASCVD event rate in those eligible by ACC/AHA but not USPSTF was 6.5 (4.9–8.5) events per 1000 person‐years, with the rate varying significantly according to baseline CAC (4.2 [2.7–6.7] events in those with CAC=0, 12.8 [8.3–19.9] events in those with CAC >100). Conclusions In MESA, compared with ACC/AHA, the USPSTF statin guidelines resulted in a 15% absolute decrease in eligibility. Participants with discordant eligibility had ASCVD rates that varied significantly according to baseline CAC, suggesting CAC could aid clinical decision making for statins in these individuals.