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Tag: CVD Risk

Reducing Cardiovascular Disease Risk with Polypills and Aspirin

Lifestyle interventions and preventative medications are central components of prevention strategies targeting cardiovascular disease (CVD) as well as attempts at lowering patient health risk factors. One possible pharmacologic intervention is the use of polypills, which has been found to improve adherence to preventive medications. Fixed-dose combination therapy in the form of a polypill is frequently used to control more than one health risk factor – such as combinations of heart disease, hypertension, type 2 diabetes, and stroke.

As part of a comprehensive strategy, reducing the risk of cardiovascular disease may be possible with the use of a polypill and aspirin combination. Emerging research published in The New England Journal of Medicine suggests that a polypill comprised of statins, multiple blood-pressure-lowering drugs, and aspirin may reduce the risk of cardiovascular disease.

Assessing Polypill Efficacy

As part of the large, international trial, a team of researchers randomly assigned participants without cardiovascular disease who had an elevated INTERHEART Risk Score to receive one of several therapeutic options or placebo. The study included a total of 5713 participants, with an average age of 64 years and 47% were males. The follow-up period was an average of 4.6 years during which the investigators monitored for the first occurrence of a major cardiovascular event or death.

The researchers used a 2-by-2-by-2 factorial design which involved a polypill, a polypill-plus-aspirin combination, or placebo drug. The polypill contained 40 mg of simvastatin, 100 mg of atenolol, 25 mg of hydrochlorothiazide, and 10 mg of ramipril. Along with the polypill or placebo, participants took either 75 mg of aspirin or placebo as well as vitamin D or placebo daily.

The study’s authors investigated the outcomes and safety of the administration of the polypill alone compared with matching placebo conditions; for aspirin alone as compared with matching placebo; and for the polypill-plus-aspirin combination compared with double placebo. In the case of polypill-only and polypill-plus-aspirin comparisons, the primary outcome was death from cardiovascular causes, myocardial infarction, stroke, resuscitated cardiac arrest, heart failure, or revascularization. For the aspirin comparison, the primary outcome measured was death from cardiovascular causes, myocardial infarction, or stroke.

Polypill-Plus-Aspirin Benefits

The analysis revealed that the primary outcome for the polypill comparison occurred in 126 participants (4.4%) of the polypill group and in 157 (5.5%) individuals in the placebo group. The researchers found that the use of the polypill alone was able to reduce cardiovascular disease by up to 21%.

Additionally, the primary outcome for the aspirin comparison occurred in 116 participants (4.1%) of the aspirin group and in 134 participants (4.7%) of the placebo group. Aspirin alone was able to reduce rates of cardiovascular death, heart attack, and stroke by 14%.

Finally, the primary outcome for the polypill-plus-aspirin comparison occurred in 59 participants (4.1%) in the combined-treatment group and 83 (5.8%) of the double-placebo group. The polypill-plus-aspirin reduced cardiovascular disease most significantly by 31%.

The study’s authors also found that low-density lipoprotein cholesterol levels were lower by approximately 19mg per deciliter and systolic blood pressure was lower by approximately 5.8 mm Hg in the polypill and polypill-plus-aspirin cohort than in patients receiving the placebo. However, they noted that the incidence of hypertension or dizziness was higher in groups receiving polypill than those in placebo, which will require further investigation.

Clinical Implications

As the latest findings indicate, the combination treatment comprised of a polypill plus aspirin may lead to a lower incidence of cardiovascular events among individuals without cardiovascular disease who experience an intermediate risk for cardiovascular conditions.

“Aspirin should be prescribed with a polypill in primary prevention for patients at intermediate risk of heart disease,” Salim Yusuf, M.D., B.S., D. Phil., co-author of the study told Science Daily. “Our study results provide important data regarding the role of the polypill in preventing the development of heart disease.”

Co-author Prem Pais, MBBS, MD, professor in the division of clinical research and training at St. John’s Research Institute in Bangalore, India, added, “We were also interested in evaluating if combining blood pressure and cholesterol reduction medications in a single pill would be effective for this population. This is a cost-effective strategy that could help meet global targets of reducing CVD by 30% by 2030.”

The combination therapy method could potentially avert between 3 and 5 million cardiovascular deaths across the globe and have a profound impact on the cardiovascular health outcomes of the population. In the future, polypills comprised of newer statins may be able to further reduce LDL cholesterol, blood pressure, and cardiovascular disease risk by over 50%, the researchers concluded.

The Impact of Sleep Patterns on Genetic Risk and Incidence of CVD

Out of the many important risk factors for cardiovascular disease, several are related to individual lifestyle patterns.  Emerging evidence  implicates that sleep behaviors may play a larger role in cardiovascular disease risk than previously thought. Individuals with unhealthy sleep habits, such as insomnia, snoring, and daytime sleepiness, may face an increased CVD risk between 10% and 40%. In addition to lifestyle habits, genetic factors contribute to CVD risk; recent evidence suggests genetic susceptibility might interact with lifestyle patterns to influence cardiometabolic health outcomes.

 To date, limited research has been conducted on the impact of various sleeping patterns on genetic risk and incidence of cardiovascular disease. Previous studies have assessed sleep behaviors individually, not taking into account the complexity and correlations of several different sleep behaviors which may play a significant role in determining risk profiles. However, whether healthy sleep patterns may mitigate the effect of genetic predisposition on cardiovascular disease incidence remains unknown.

 In an effort to clarify the association between these two CVD risk factors, a team of researchers led by Lu Qi, MD, PhD, director of the Obesity Research Center at Tulane University,  evaluated the impact of sleep patterns on cardiometabolic outcome “Since we know that sleep behaviors are complex and interact with each other, we wanted to consider them all together,” said Dr. Qi, MD, PhD, in an interview with Medscape Cardiology.

Sleep Patterns, Genetic Risk, and Incident CVD

To quantify the association of combined sleep patterns and genetic risk with the incidence of cardiovascular disease,the team of researchers evaluated over 385,000 participants with no prior history of cardiovascular disease. Participants’ data were sourced from UK Biobank – a large, prospective study of individuals between 37 and 73 years of age who provided blood samples for genotyping as well as self-reported sleep and other health-related behaviors.

 Researchers determined a healthy sleep score based on five sleep behavior factors – which included chronotype, duration, insomnia, snoring, and excessive daytime sleepiness. Low-risk groups were identified as participants with early chronotype as well as those who slept 7-8 hours per day, never or rarely experienced insomnia, did not snore, and did not report frequent excessive daytime sleepiness. The study’s authors then calculated the weighted genetic risk scores of cardiovascular disease by analyzing single-nucleotide polymorphisms with a known association with coronary heart disease and stroke.

 

Increased Risk Associated with Poor Sleep Quality

 The team’s findings were published in the European Heart Journal and revealed a decrease in the risk for heart disease and stroke correlated to healthy sleep patterns, even among participants with a high genetic risk. During the median follow-up period of 8.5 years, there were 7,280 documented incidents of CVD, of which 4,667 were cases of coronary heart disease and 2,650 were stroke cases. Compared with participants who had a sleep score between 0 and 1, participants with a score of 5 experienced a reduced risk of CVD, CHD, and stroke at rates of 35%, 34%, and 34%, respectively.

 Approximately 10% of the cardiovascular events that occurred in this cohort could be attributed to poor sleep patterns, the researchers wrote. Furthermore, participants with poor sleep patterns and a high genetic risk showed the highest risk of CHD and stroke.

 Researchers also found an increased risk for coronary heart disease as genetic risk factors increased and healthy sleep patterns decreased. In the most extreme cases, participants with high genetic risk – who also had poor sleeping habits – faced a 2.5 times increased risk for coronary heart disease compared with those with low genetic risk and healthy sleep patterns. Comparatively, participants who entered the study with a low genetic risk experience an increase in risk as a result of poor sleep behaviors.

 Although the study was observational in nature and the association between sleep patterns and cardiovascular events cannot be considered causal, the latest findings reveal the potential significance of healthy sleep behaviors – particularly for patients with high genetic predispositions for cardiovascular disease. Dr. Qi and colleagues assessed the population attributable risk, which implicated that if the associations were indeed causal, then “more than 10% of CVD, CHD, and stroke events would not have occurred if all participants had been in the low-risk group for all five sleep factors.” Thus, promoting healthy sleep patterns and improving the treatment of sleep disorders may provide to be a vital prevention method of cardiovascular disease, regardless of the patient genetic risk profile.