Genomic technologies and Optimum Heart Care

The state of genomic knowledge of CVDs and stroke has expanded dramatically in recent years. Since our scientific statement was published in 2007, there has been rapid evolution of the genomic technologies, enabling a proliferation of GWASs investigating common, complex diseases, including CVDs and stroke. Because the number of associations that are tested within the GWAS platforms is large and most associations are weak, the process of conducting these studies has also evolved dramatically during this same period. Researchers from around the world have come together as collaborators both to replicate (to reduce the potential for type I errors) and to meta-analyze data (to have statistical power to identify weak effects).

We are on the precipice of further expansion to sequencing the whole genome of patients and large population cohorts to detect additional and rare variants predisposing to disease. Therefore, the next 5-year period will be consumed with mining the wealth of data that will be generated by this next phase of research. Additionally, progress in other “omics” fields will inform these sequence data to help in understanding function. Finally, the environment will be given more attention as we identify solutions to disease prevention and treatment.

We anticipate that in the near future we will determine genetically based disease susceptibility within individuals, families, and populations. We conclude this statement with recommendations intended to guide clinical and public health practice, to foster research, and to prepare both researchers and healthcare practitioners for the changes likely to occur as genetics are translated to the population and the clinical setting.

Currently Relevant Recommendations to Enable Future Discoveries and Optimization of Care

  • Continue to develop and implement research that accelerates the translation of genomic discoveries to the prevention and treatment of CVDs and stroke. We suggest including the following:

  • —Incentives for researchers to collect DNA and consent to use specimens and data in future studies

  • —Expansion of biorepositories linked to electronic health records

  • —Translational genomic research of all types, bidirectionally, from bench to population

  • —Support of multidisciplinary, collaborative research programs

  • —Support of expanded genetic counseling training opportunities

  • Continue these research agendas to follow up and use genetic discoveries:

  • —Characterize genes and genetic variants that are associated with CVD across individuals and populations from multiple ethnic groups both at population levels and in functional mechanistic studies

  • —Determine how environmental factors (including behaviors and drugs) interact with genetic variants to influence CVD

  • —Expand pharmacogenetic research to identify genetic variants that predict adverse drug reactions and better efficacy

  • —Develop new technologies in CVD characterization, risk assessment, and outcome prediction and test these technologies in randomized, controlled trials

  • Conduct implementation research to understand the clinical utility of genetic screening because this has not yet been systematically tested in the majority of cases. Prepare proactively for effective genetic screening programs:

  • —Establish prevalence and family history criteria that would trigger screening programs in at-risk populations

  • —Create standards and laboratory oversight mechanisms for genetic testing facilities

  • —Match appropriate treatment guidelines to particular genetic susceptibility findings

  • —Assess the potential cost-effectiveness of genetic screening programs

  • Educate our workforce:

  • —Train clinicians to understand genetic screening tests for complex CVDs and stroke and when to refer to a genetics clinic or engage a genetic counselor

  • —Include genetics in graduate educational curricula

  • —Educate researchers in genetics, computational biology, and statistical genetics

Source:

http://circ.ahajournals.org/content/129/25_suppl_2/S1/T4.expansion.html

2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults

  1. Focus on ASCVD Risk Reduction: 4 Statin Benefit Groups

    1. This guideline is based on a comprehensive set of data from RCTs from which 4 statin benefit groups were identified that focus efforts to reduce ASCVD events in secondary and primary prevention.

    2. This guideline identifies high-intensity and moderate-intensity statin therapy for use in secondary and primary prevention.

  2. A New Perspective on LDL-C and/or Non–HDL-C Treatment Goals

    1. The Expert Panel was unable to find RCT evidence to support continued use of specific LDL-C or non–HDL-C treatment targets.

    2. The appropriate intensity of statin therapy should be used to reduce ASCVD risk in those most likely to benefit.

    3. Nonstatin therapies, as compared with statin therapy, do not provide acceptable ASCVD risk-reduction benefits relative to their potential for adverse effects in the routine prevention of ASCVD.

  3. Global Risk Assessment for Primary Prevention

    1. This guideline recommends use of the new Pooled Cohort Equations to estimate 10-year ASCVD risk in both white and black men and women.

    2. By more accurately identifying higher-risk individuals for statin therapy, the guideline focuses statin therapy on those most likely to benefit.

    3. It also indicates, on the basis of RCT data, those high-risk groups that might not benefit.

    4. This guideline recommends a discussion between clinicians and patients before initiation of statin therapy.

  4. Safety Recommendations

    1. This guideline used RCTs to identify important safety considerations in individuals receiving treatment of blood cholesterol to reduce ASCVD risk.

    2. Using RCTs to determine statin adverse effects facilitates understanding of the net benefit from statin therapy.

    3. This guideline provides expert guidance on management of statin-associated adverse effects, including muscle symptoms.

  5. Role of Biomarkers and Noninvasive Tests

    1. Treatment decisions in selected individuals who are not included in the 4 statin benefit groups may be informed by other factors as recommended by the Risk Assessment Work Group and Blood Cholesterol Expert Panel.

  6. Future Updates to the Blood Cholesterol Guideline

    1. This is a comprehensive guideline for the evidence-based treatment of blood cholesterol to reduce ASCVD risk.

    2. Future updates will build on this foundation to provide expert guidance on the management of complex lipid disorders and incorporate refinements in risk stratification based on critical review of emerging data.

    3. RCTs comparing alternative treatment strategies are needed in order to inform future evidence-based guidelines for the optimum ASCVD risk-reduction approach.

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