Haptoglobin genotype is a risk factor for coronary artery disease in prediabetes: A case-control study.

Objective: Coronary artery disease (CAD) prediction remains inconsistent with many unappreciated risk factors. Haptoglobin genotype determines the haptoglobin protein's effectiveness to bind free hemoglobin and prevent oxidative stress, a contributor to atherosclerosis. The haptoglobin 2-2 genotype increases the prevalence of cardiovascular disease (CVD) approximately five times compared to the 1-1 genotype in individuals with diabetes. The risk is unknown in prediabetes. The purpose of this study was to determine an association between haptoglobin genotype and CAD in prediabetes. Methods: The researchers used case-control convenience sampling from two cardiovascular disease prevention clinics in Memphis, TN, and Spokane, WA, from January 1, 2016 to March 31, 2020. Participants were ages 35-70, had prediabetes, and free of chronic inflammatory or infectious diseases. Cases had a history of subclinical or clinical CAD, while controls did not have a history of CAD. Differences between cases and controls and among haptoglobin genotypes were analyzed using t-tests and ANOVA for continuous variables and chi-square or Fisher's exact tests for categorical variables. Associations among Hp genotypes and CAD were estimated using logistic regression. Results: The sample (N = 178; 72 cases and 106 controls) was 96 % white and 64 % male. Cases had lower total cholesterol (p = 0.0001) and high-sensitivity C-reactive protein (p = 0.021). Except for CAD, haptoglobin genotype was independent of any demographic or clinical variable. Haptoglobin 2-2 genotype had 4.0 times higher odds of CAD than haptoglobin 1-1 (p = 0.01). Conclusion: Haptoglobin 2-2 genotype had approximately four times higher odds of having CAD compared to the haptoglobin 1-1 genotype. Cases had more desirable clinical profiles, likely attributable to more aggressive treatment of traditional risk factors than controls. Haptoglobin genotype is a potentially important CAD risk factor in prediabetes (88 million Americans). Further studies are needed for interventions to reduce the oxidative stress associated with the Hp 2-2 genotype and glycosylated hemoglobin and for CAD reduction.

Myeloperoxidase: A Circulating Marker of Inflammation and Tooth Infection.

BACKGROUND: Atherosclerotic cardiovascular disease and tooth infection are common in primary care, and both significantly reduce quality of life. Our study aimed to examine signs of vascular inflammation associated with loss of tooth vitality before and after a single tooth extraction. METHODS: An observational cohort study was performed with adults who had a nonvital tooth and an indicated desire for tooth extraction. Concentrations of total cholesterol, high-density lipoprotein-cholesterol, high-sensitivity C-reactive protein (hs-CRP), myeloperoxidase (MPO), and troponin T were measured in venous blood serum or plasma at baseline and 6-weeks after tooth extraction. RESULTS: Circulating hs-CRP levels were > 3 mg/dL in 15 participants (68.2%) and MPO levels were > 350 pmol/L in 9 (40.9%) of 22 participants at baseline. After tooth extraction (n = 18), MPO levels decreased significantly compared with baseline (P < .00006) and hs-CRP levels moved directionally downward. The response rate for MPO was 88.9% (confidence interval: 65.1%-98.6%) from visit 1 to visit 2. Those with high MPO levels at baseline demonstrated larger reductions in MPO levels by visit 2 than those with lower baseline MPO levels (r = .81; P < .0001). A total of 13 individuals (72.2%) achieved MPO levels < 350 pmol/L and 11 (61.1%) achieved hs-CRP levels < 3 mg/dL at visit 2. Total cholesterol, high-density lipoprotein-cholesterol, and troponin T levels did not significantly change from visit 1 to visit 2. CONCLUSION: A link between dental infection and circulating levels of inflammation was observed, suggesting that oral infection could be a risk factor for atherosclerotic cardiovascular disease.

The critical issue linking lipids and inflammation: Clinical utility of stopping oxidative stress.

The formation of an atheroma begins when lipoproteins become trapped in the intima. Entrapped lipoproteins become oxidized and activate the innate immune system. This immunity represents the primary association between lipids and inflammation. When the trapping continues, the link between lipids and inflammation becomes chronic and detrimental, resulting in atherosclerosis. When entrapment ceases, the association between lipids and inflammation is temporary and healthy, and the atherogenic process halts. Therefore, the link between lipids and inflammation depends upon lipoprotein retention in the intima. The entrapment is due to electrostatic forces uniting apolipoprotein B to polysaccharide chains on intimal proteoglycans. The genetic transformation of contractile smooth muscle cells in the media into migratory secretory smooth muscle cells produces the intimal proteoglycans. The protein, platelet-derived growth factor produced by activated platelets, is the primary stimulus for this genetic change. Oxidative stress is the main stimulus to activate platelets. Therefore, minimizing oxidative stress would significantly reduce the retention of lipoproteins. Less entrapment decreases the association between lipids and inflammation. More importantly, it would halt atherogenesis. This review will analyze oxidative stress as the critical link between lipids, inflammation, and the pathogenesis of atherosclerosis. Through this perspective, we will discuss stopping oxidative stress to disrupt a harmful association between lipids and inflammation. Numerous therapeutic options will be discussed to mitigate oxidative stress. This paper will add a new meaning to the Morse code distress signal SOS-stopping oxidative stress.

Cardiovascular Prevention: Migrating From a Binary to a Ternary Classification.

Migrating from a binary approach to risk assessment to a ternary model of disease identification allows for individualized, optimal disease management. Redefining the disease/inflammatory approach has been proven to identify, stabilize, and regress atherosclerosis while adding understanding to the progression of vascular disease. Our previously published results show the beneficial effect of comprehensive, evidence-based management on subclinical atherosclerosis and vulnerable plaque. We argue that this approach does not mitigate the value of utilizing standard risk factor identification, but rather augments it for the benefit of the individual patient.

Microvascular disease confers additional risk to COVID-19 infection.

The majority of fatalities thus far in the COVID-19 pandemic have been attributed to pneumonia. As expected, the fatality rate reported in China is higher in people with chronic pulmonary disease (6.3%) and those who have cancer (5.6%). According to the American College of Cardiology Clinical Bulletin "COVID-19 Clinical Guidance for the CV Care Team", there is a significantly higher fatality rate in people who are elderly (8.0% 70-79 years; 14.8% ≥80 years), diabetic (7.3%), hypertensive (6.0%), or have known cardiovascular disease (CVD) (10.5%). We propose a biological reason for the higher mortality risk in these populations that is apparent. We further present a set of pathophysiological reasons for the heightened danger that could lead to therapies for enhanced management and prevention.

Precision Healthcare of Type 2 Diabetic Patients Through Implementation of Haptoglobin Genotyping.

It is well-recognized that there is a need for medicine to migrate to a platform of delivering preventative care based on an individual's genetic make-up. The US National Research Council, the National Institute of Health and the American Heart Association all support the concept of utilizing genomic information to enhance the clinical management of patients. It is believed this type of precision healthcare will revolutionize health management. This current attitude of some of the most respected institutes in healthcare sets the stage for the utilization of the haptoglobin (Hp) genotype to guide precision management in type 2 diabetics (DM). There are three main Hp genotypes: 1-1, 2-1, 2-2. The Hp genotype has been studied extensively in (DM) and from the accumulated data it is clear that Hp should be considered in all DM patients as an additional independent cardiovascular disease (CVD) risk factor. In DM patients Hp2-2 generates five times increased risk of CVD compared to Hp1-1 and three times increased risk compared to Hp2-1. Data has also shown that carrying the Hp2-2 gene in DM compared to carrying an Hp1-1 genotype can increase the risk the microvascular complications of nephropathy and retinopathy. In addition, the Hp2-2 gene enhances post percutaneous coronary intervention (PCI) complications such as, in stent restenosis and need for additional revascularization during the first-year post PCI. Studies have demonstrated significant mitigation of CVD risk in Hp2-2 DM patients with administration of vitamin E and maintaining tight glycemic control. CVD is the leading cause of death and disability in DM as well-representing a huge financial burden. As such, evaluating the Hp genotype in DM patients can enhance the predictability and management of CVD risk.

High-risk periodontal pathogens contribute to the pathogenesis of atherosclerosis.

Periodontal disease (PD) is generated by microorganisms. These microbes can enter the general circulation causing a bacteraemia. The result can be adverse systemic effects, which could promote conditions such as cardiovascular disease. Level A evidence supports that PD is independently associated with arterial disease. PD is a common chronic condition affecting the majority of Americans 30 years of age and older. Atherosclerosis remains the largest cause of death and disability. Studies indicate that the adverse cardiovascular effects from PD are due to a few putative or high-risk bacteria: Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola or Fusobacterium nucleatum There are three accepted essential elements in the pathogenesis of atherosclerosis: lipoprotein serum concentration, endothelial permeability and binding of lipoproteins in the arterial intima. There is scientific evidence that PD caused by the high-risk pathogens can influence the pathogenesis triad in an adverse manner. With this appreciation, it is reasonable to state PD, due to high-risk pathogens, is a contributory cause of atherosclerosis. Distinguishing this type of PD as causal provides a significant opportunity to reduce arterial disease.

Effect of comprehensive cardiovascular disease risk management on longitudinal changes in carotid artery intima-media thickness in a community-based prevention clinic.

INTRODUCTION: The aim of the study was to examine changes in carotid intima-media thickness (CIMT) and carotid plaque morphology in patients receiving multifactorial cardiovascular disease (CVD) risk factor management in a community-based prevention clinic. Quantitative changes in CIMT and qualitative changes in carotid plaque morphology may be measured non-invasively by ultrasound. MATERIAL AND METHODS: This is a retrospective study on a cohort of 324 patients who received multifactorial cardiovascular risk reduction treatment at a community prevention clinic. All patients received lipid-lowering medications (statin, niacin, and/or ezetimibe) and lifestyle modification. All patients underwent at least one follow-up CIMT measurement after starting their regimen. Annual biomarker, CIMT, and plaque measurements were analyzed for associations with CVD risk reduction treatment. RESULTS: Median time to last CIMT was 3.0 years. Compared to baseline, follow-up analysis of all treatment groups at 2 years showed a 52.7% decrease in max CIMT, a 3.0% decrease in mean CIMT, and an 87.0% decrease in the difference between max and mean CIMT (p < 0.001). Plaque composition changes occurred, including a decrease in lipid-rich plaques of 78.4% within the first 2 years (p < 0.001). After the first 2 years, CIMT and lipid-rich plaques continued to decline at reduced rates. CONCLUSION: In a cohort of patients receiving comprehensive CVD risk reduction therapy, delipidation of subclinical carotid plaque and reductions in CIMT predominantly occurred within 2 years, and correlated with changes in traditional biomarkers. These observations, generated from existing clinical data, provide unique insight into the longitudinal on-treatment changes in carotid plaque.

Commentary on an Innovative Interprofessional Dental Practice for 2026.

UNLABELLED: An innovative interprofessional model is described for the delivery of dental care in the year 2026 to optimize efficiency and profitability while enhancing quality of care. BACKGROUND: The dental practice of tomorrow may look different than today. Although not broken, the current system can be improved in efficiency and effectiveness. Although traditional private practices will continue to exist and many will thrive over the next decades, they may not present the optimal model for dental practice. To manage complex patient needs, a more collaborative model of multidisciplinary, interprofessional clinical teams capable of treating patients comprehensively has been suggested by the authors. They explore an alternative model of practice that may be possible in the next 10 years to better serve patients and improve outcomes while honoring the role of practitioners. METHODS: Landmark publications and reviews are used to examine evidence showing the potential benefits of an innovative interprofessional approach to the delivery of care in the oral health care setting. CONCLUSIONS: By examining key studies, the authors provide commentary on the potential for enhanced efficiency, profitability, and quality of care in the oral health care setting through a collaborative model of multidisciplinary, interprofessional clinical teams capable of treating patients comprehensively.

Eight-year outcomes of a program for early prevention of cardiovascular events: a growth-curve analysis.

BACKGROUND: Early identification of cardiovascular diseases allows us to prevent the progression of these diseases. The Bale/Doneen Method, a prevention and treatment program for heart attacks and ischemic strokes, has been adopted nationally in primary care and specialty clinics. OBJECTIVES: The main purpose of this study was to evaluate the effect of the Bale/Doneen Method on lipoproteins and carotid intima-media thickness (IMT) for cardiovascular disease prevention and reduction. A secondary purpose was to illustrate the use of latent growth-curve analysis in studying trajectories of clinical outcomes and biomarkers in individual patients over time. METHOD: This retrospective analysis is based on 576 patients at a nurse-managed ambulatory clinic who received the heart attack prevention and treatment program from 2000 to 2008. All patients were white; 61% were men; mean age was 55.5 years. Outcome measures include hemoglobin A1c, fasting blood sugar, plaque burden score (PBS), high-density lipoprotein, low-density lipoprotein (LDL), mean carotid artery IMT, and lipoprotein-associated phospholipase A2 test results. Latent growth-curve analysis was used in modeling changes in these outcome measures. RESULTS: On average, mean IMT score decreased by 0.01 per year (P < .001), PBS decreased by 0.17 per year (P < .001), LDL decreased by 5.19 per year (P < .001), and lipoprotein-associated phospholipase A2 decreased by 3.6 per year (P < .05). Hemoglobin A1c increased by 0.04 per year (P < .001). Significant sex and age differences in the initial level and/or rate of change of mean IMT, PBS, fasting blood sugar, high-density lipoprotein, and LDL scores were found. DISCUSSION: The current findings suggest that the Bale/Doneen Method is effective in generating a positive effect on the atherosclerotic disease process by achieving regression of disease in the carotid arteries.

Carotid intima-media thickness testing as an asymptomatic cardiovascular disease identifier and method for making therapeutic decisions.

Cardiovascular disease (CVD) is the leading cause of death and disability in the United States. Although current therapies can reduce the risk for CVD, they are only given to patients who are considered to be at risk, and are therefore only beneficial if a patient's risk is accurately predicted before he or she sustains a cardiovascular (CV) event. Unfortunately, even relatively accurate risk factor analyses, such as the Reynolds Risk Score algorithm, fail to identify some patients who will sustain a CV event within 10 years. In contrast, the presence of an atheroma is an absolute predictor for the potential of an atherothrombotic event to occur, and it is therefore reasonable to anchor clinical decisions based on this knowledge. Carotid intima-media thickness (CIMT) testing via B-mode ultrasound is a safe, simple, and inexpensive method for evaluating CV risk by measuring the combined thickness of the intimal and medial layers of the arterial wall. Use of CIMT testing can also detect marked thickening of the arterial wall, possibly indicating plaques or atheromas that are associated with accelerated atherosclerotic disease and increased risk for coronary artery disease, myocardial infarction, and stroke. These characteristics make CIMT a practical supplemental method that physicians can use when making decisions. Moreover, the ability of CIMT testing to identify and quantify atherosclerotic disease has led to the adoption of CIMT as a surrogate endpoint in clinical trials, allowing the efficacy of new drugs to be assessed much more rapidly than would be possible by focusing solely on CV event or mortality rates. To date, several trials have provided evidence to indicate that some CVD therapies slow, stop, or reverse the progression of CIMT. Although many of these studies show that changes in CIMT predict future CV events, the value of CIMT testing in CVD risk assessment is still vigorously debated. In this article, we clarify the utility of CIMT testing for risk classification and reexamine its usefulness as a method for assessing therapeutic efficacy.

Niacin-a critical component to the management of atherosclerosis: contemporary management of dyslipidemia to prevent, reduce, or reverse atherosclerotic cardiovascular disease.

Niacin (nicotinic acid) is the most effective agent for raising high-density lipoprotein cholesterol levels and can improve the entire lipid panel in patients with dyslipidemia. Niacin-containing regimens are among the few treatments studied for dyslipidemia that have both elicited significant reductions in atherosclerotic progression (by angiography or imaging) and also significantly reduced (by approximately 90% vs control) the incidence of cardiovascular events in a single clinical trial. However, cutaneous flushing-an uncomfortable but typically transient adverse effect of niacin-often results in patient nonadherence with this potentially life-saving therapy. Effective counseling regarding the highly favorable benefit-risk ratio for niacin and management strategies such as careful dose escalation, follow-up monitoring, regimen adjustments, and the use of treatment adjuncts (eg, aspirin) can improve patient adherence with niacin therapy. Clinicians are uniquely positioned to provide such counseling to appropriate patients for niacin treatment and hence encourage wider use of this important and necessary cardioprotective medication.