Challenges and Opportunities in Coronary Artery Disease
Jacques Fair, Esperanza Acuna, and Robert Roberts
Abstract
Coronary artery disease (CAD) is the number one cause of death in the world. It is estimated that 50% of Americans will experience a cardiac event in their lifetime. The underlying pathology leading to coronary artery disease and its clinical manifestations, such as angina, myocardial infarction, and sudden death, is coronary atherosclerosis. While the disease is not usually manifested clinically until the sixth or seventh decade, the underlying pathology is initiated as early as the second or third decade. Numerous randomized clinical trials have shown cardiac morbidity and mortality can be prevented by lowering the risk of known conventional risk factors for CAD, such as decreasing plasma cholesterol or controlling hypertension. Secondary prevention of these conventional risk factors has been very effective; however, primary prevention has been shown to be even more effective. A major barrier to primary prevention is the lack of markers to detect among young, asymptomatic individuals at risk for CAD. The conventional risk factors are often not present until the sixth or seventh decade, which could be late for primary prevention. Genetic predisposition accounts for 50% of the risk for CAD. Recently, over 200 genetic risk variants predisposing to CAD have been discovered. Based on these variants, one can express the genetic risk for CAD in a single number referred to as the Polygenic Risk Score (PRS). The PRS has been evaluated in over one million individuals and shown that those with high genetic risk have the highest incidence of heart disease and can be reduced by 40–50% by utilizing drugs (statins and PCSK9 inhibitors) or lifestyle changes (a favorable diet and increased exercise). The genetic risk for CAD is determined at conception and thus can be predicted anytime from birth onward. The PRS detection of young, asymptomatic individuals based on the PRS enables one to implement early primary prevention. Adoption of the PRS to risk stratify for CAD could represent a paradigm shift in the prevention of this pandemic disease.
Robert Roberts and Esperanza Acuna
Abstract
Coronary artery disease, the number one cause of death in the world, is highly amenable to primary and secondary prevention. Primary prevention is limited because of a lack of biomarkers to detect CAD in its asymptomatic phase. Conventional risk factors, such as hypertension, are not evident until the 6th or 7th decade, which may be late for primary prevention, particularly in males. The recent discovery of genetic risk variants for CAD has the potential, through risk stratification, to detect individuals most appropriate for primary prevention. First, genetic risk accounts for about 50% of predisposition to CAD; second, it is determined at conception and not influenced by age since DNA does not change in one’s lifetime. Thirdly, genetic risk can be determined at any time from birth onward, which is close to ideal for early primary prevention. A review of the literature shows genetic risk can be summarized in a single number, referred to as the polygenic risk score (PRS), and used to stratify risk for CAD. The PRS has been evaluated in over 1 million individuals, and those in the top 20% exhibit a one-to-four-fold greater risk for CAD than those in the bottom 20%. More importantly, clinical studies have shown that decreasing plasma LDL-C or modifying lifestyle decreases the genetic risk for CAD by 50%. The polygenic risk score, obtained from a single blood sample, does not need to be repeated in one’s lifetime. Furthermore, the genetic risk captured by the PRS is relatively independent of conventional risk factors, including family history. The current PRS was determined primarily for individuals of European decent, which can be a limitation to its use in other ethnic groups. However, the results of trials ongoing in several ethnic groups will soon be available. We propose that primary prevention be initiated early in life in individuals in the top 20% of the PRS. The test is relatively inexpensive, and generic drug therapy is also inexpensive. The use of the PRS to risk stratify for CAD would be a paradigm shift for the implementation of early primary prevention of CAD.
Lisa Ferraz, Andreia Fernandes, Ana Faustino, Simão Carvalho, Adriana Pacheco, and Ana Neves
Abstract
Background: Although dobutamine stress echocardiography (DSE) has a high specificity, there is still a subset of patients with false positive tests (FP); whether these results have prognostic value remains unclear.
Aims: To identify the clinical and echocardiographic predictors of FP on DSE and to evaluate the prognostic impact of FP on DSE.
Methods: Retrospective study of 355 consecutive patients who underwent DSE for ischemia assessment over a one-year period: 134 (37,7%) women, 70,3 ± 0,57 years. Demographics, risk factors, clinical and laboratory parameters, and DSE variables were evaluated. Patients were divided into 2 groups regarding the presence (FP+) or absence (FP0) of an FP result on DSE, and a comparative analysis was performed to characterize the groups and identify potential predictors of FP results. Patients were followed for 2 years to assess acute myocardial infarction, hospitalization for acute heart failure (HF), and mortality.
Results: The FP rate was 4.5%. Compared to FP0, patients in group FP+ were younger, baseline wall motion abnormalities were more frequent, they had higher mean blood pressure values at rest and peak stage, and they often had a hypertensive response. There were no significant differences regarding previous coronary artery disease, medication, or a complete left bundle branch block. By multivariate analysis, only mean blood pressure values at rest (OR 0,01; 95%CI 0,005-0,02; p=0,003) and at peak stage (OR 0,02; 95%CI 0,000-0,004; p=0,003) were independent predictors of FP. During follow-up, acute myocardial infarction (FP+: 12.5% vs. FP0: 1.8%, p = 0.046), HF (FP+: 6.3% vs. FP0: 11.5%, p = 0.44), and mortality (FP+: 6.3% vs. FP0: 6.2%, p = 0.65). After adjustment for age, sex, and comorbidities, there were no differences between the groups regarding HF and mortality, but the group FP+ maintained a higher rate of acute myocardial infarction (OR 0,21; 95%CI 0,065-0,354; p = 0,005).
Conclusion: The AFP result on DSE was associated with higher mean blood pressure values during the test and higher rates of acute myocardial infarction during follow-up. Therefore, this result on DSE should be used as a risk marker for ischemic events. It can identify patients who may benefit from aggressive risk factor control and careful clinical follow-up.
Gerald Dorros, M.D., FACC
Abstract
The unintended consequences of the US Centers for Medicare & amp; Medicaid Services’ (CMS) decision not to pay for invasive diagnostic FFR (Fractional Flow Reserve) have precluded its routine diagnostic use in hundreds of thousands of Medicare beneficiaries who suffered inappropriate coronary stent procedures (PCI) that worsened Medicare beneficiaries’ clinical outcomes: 20% of PCI patients have no or uncertain clinical indications but are nevertheless operated upon, and 33% of potential PCI stenoses are non-ischemic and require no PCI. These unnecessary PCIs, often confounded by aging’s anatomical and comorbid complexities, result in preventable complications, repeat procedures, worse clinical outcomes, unwarranted deaths, and an avoidable $1 billion annual expenditure. The best coronary artery disease (CAD) patient care requires astute clinical assessment coupled with diagnostic physiologic ischemic lesion categorization, which directly links lesion treatment to patient management. CMS’ unrealistic expectation that their bundled payment to a single healthcare provider would motivate providers to maximize their profits through efficiently coordinated and improved care was naive; this foolish policy of eschewing invasive FFR payments and expecting providers to absorb the FFR pressure wire’s cost has inflicted potential irreparable harm on all Medicare beneficiaries. CMS has forsaken its mission to attain the “highest level of health for all people, where everyone has a fair and just opportunity to attain their optimal health regardless of race, ethnicity, disability, sexual orientation, gender identity, socioeconomic status, geography, preferred language, or other factors that affect access to care and health outcomes”.
George Trad, MD, Rasiq Zackria, DO, Syed Abdul Basit, MD, and John K. Ryan, MD
Abstract
Necrotizing pancreatitis (NP) is a life-threatening complication of acute pancreatitis. It requires an extended hospital stay, aggressive management, and a higher risk of mortality. Risk factors such as comorbidities in the patient’s history, including a history of coronary artery disease and cerebrovascular disease, can increase the risk of developing necrotizing pancreatitis. The presentation of necrotizing pancreatitis is similar to acute pancreatitis, but specific labs such as hematocrit levels can be monitored to anticipate the development of necrotizing pancreatitis. In addition, diagnostic imaging must be obtained to classify necrotizing pancreatitis and aid in management choice. Fluid hydration, adequate pain management, and nutritional support are the principles of treating necrotizing pancreatitis. Deciding whether to drain the necrotic collection or not is usually determined based on the type of necrosis present and whether it is infected. Infected necrotizing pancreatitis can also occur, and patients usually need to be monitored closely with appropriate antibiotics for a long duration. Patients affected by necrotizing pancreatitis can potentially develop complications that can lead to devastating outcomes. Necrotizing pancreatitis complications can occur due to an inflammatory reaction on the adjacent structure, such as splanchnic vein thrombosis, gastrointestinal fistula, or an inflammatory reaction within the pancreas leading to an exocrine and an endocrine pancreatic insufficiency. We present here a literature review of necrotizing pancreatitis and the complications that can arise from it.
