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.

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.

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.

Optimizing hypertension management in underserved rural populations.

Rural populations across the United States have an increased likelihood of developing hypertension and diabetes, which are significant risk factors for cardiovascular disease (CVD), including stroke and myocardial infarction. Limited access to care due to geography or socioeconomic status significantly impairs control of hypertension in rural populations, resulting in poor health outcomes. Epidemiological studies suggest that the prevalence of uncontrolled hypertension and poor glycemic control are affected by race, increasing age, and residence in the rural southeastern United States. Optimization of the delivery of rural health care is needed to improve outcomes in patients with hypertension. New strategies such as programs targeting therapeutic inertia, home-based monitoring of blood pressure (BP), and Internet-based communication programs may significantly improve BP control rates among rural patients. Among hypertensive medications, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are recommended by consensus guidelines and may be particularly effective in rural, minority populations due to their secondary effects on decreasing CVD.

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.

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.

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.

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.

Carotid intima-media thickness: knowledge and application to everyday practice.

Heart disease is the primary cause of death in the United States. Fortunately, intervention measures can reduce the risk of cardiovascular disease (CVD) after a patient has been accurately assessed. Atherosclerotic disease, one of the driving forces behind CVD, is not always detected by traditional risk assessment. Carotid intima-media thickness (CIMT), as measured by B-mode ultrasound, is a surrogate marker for atherosclerosis and can be used to detect an accelerated disease process and subclinical disease. Advantages of CIMT are that it is noninvasive, relatively inexpensive, and can be repeatedly performed with no adverse effects on the patient. Carotid intima-media thickness is associated with CVD and is an independent predictor of stroke and myocardial infarction. Therefore, CIMT is valuable for clarifying CVD risk, particularly for patients with intermediate risk by conventional risk assessment. Screening for subclinical disease even in low-risk patients may have benefit, especially for those with a family history of premature CVD or those with any of the National Cholesterol Education Program risk factors. The detection of subclinical atherosclerosis allows the physician to implement prevention efforts prior to a devastating CVD event and to investigate possible reasons for increased arterial thickening, such as an occult underlying insulin-resistant condition or residual lipid risk markers. Treatment with several types of drugs has been demonstrated to halt the progression or even reduce CIMT. Carotid intima-media thickness is currently limited by the lack of standardized protocols that may affect reproducibility from measure to measure. Efforts to draft a standardized protocol are underway by the Society of Atherosclerosis Imaging and Prevention that will address this issue. Carotid intima-media thickness provides a valuable tool for physicians to clarify the CVD risk of their patients. Practical implications of CIMT for everyday clinical practice are addressed.