Association of physical activity and trajectories of physical activity with cardiovascular disease.

INTRODUCTION: Prolonged sedentary life existence is associated with increased incidence of cardiovascular disease (CVD), coronary heart disease (CHD), obesity, type 2 diabetes mellitus (T2DM), hypertension, heart failure (HF), and all-cause mortality. On the contrary, regular exercise is known from antiquity to be associated with beneficial cardiovascular (CV) effects and decreased mortality. AREAS COVERED: The cardiovascular (CV) benefits of exercise have been confirmed by many studies, but the trajectories of the different modes of PA are not well recognized. In order to examine the different modalities of exercise and its long-term trajectories, a Medline search of the English literature was conducted between 2015 and 2022 and 60 pertinent papers were selected for review. EXPERT OPINION: Careful review of the selected papers showed that the beneficial CV effects of PA are mediated through several favorable modifications of molecular and clinical factors. Also, any type of physical activity in conjunction with lifestyle adjustments is associated with decreased incidence of CVD, CHD, obesity, T2DM, hypertension, HF, and all-cause mortality. In addition, the long-term trajectories regarding the duration and the level of exercise are associated with greater beneficial CV effects, with even the resumption of discontinued exercise can lead to beneficial CV effects.

Beneficial cardiovascular and remodeling effects of SGLT 2 inhibitors.

INTRODUCTION: This paper intended to review the data regarding the multipotential effects of the sodium-glucose cotransporter 2 (SGLT 2) inhibitors, their cardiovascular effects, and their mechanism of action. AREAS COVERED: The SGLT2 inhibitors exert their beneficial antidiabetic and cardioprotective effects through increased glucose excretion from the kidneys, blood pressure and weight lowering, vasodilation and other potential beneficial effects. They have been used for the treatment of patients with type 2 diabetes mellitus (T2DM) as well as in patients with cardiovascular disease (CVD), coronary artery disease (CAD),and heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). To get a better understanding of their mechanism of action for their multiple cardiovascular protective effects, a Medline search of the English language literature was conducted between 2015 and February 2022 and 46 pertinent papers were selected. EXPERT OPINION: The analysis of data clearly demonstrated that the use of the SGLT2 inhibitors besides their antidiabetic effects, provide additional protection against CVD, CAD, and HFrEF and HFpEF, and death, but not stroke, in both diabetic and non-diabetic patients. Therefore, they should be preferably used for the treatment of patients with T2DM with preexisting CVD, CAD, and HFrEF and HFpEF.

Antihypertensive and cardioprotective effects of three generations of beta-adrenergic blockers: an historical perspective.

There are currently three generations of beta-adrenergic blockers for the treatment of hypertension and cardiovascular diseases. The 1st generation caused vasoconstriction and bronchoconstriction due to ß1 + ß2 receptor blockade and unopposed α1 receptors. The 2nd generation of beta-blockers has lesser adverse effects than the 1st generation with the 3rd generation beta-blockers having much lesser effects than the other two generations. Current US and International guidelines do not recommend beta-blockers as first-line therapy of hypertension, but only in the presence of coronary artery disease or heart failure due to their lesser antihypertensive effect. These recommendations are disputed by several older and recent studies which have shown that the beta-blockers are effective and safe for the treatment of hypertension and could be used as first-line therapy. To clarify this issue a Medline search of the English language literature was conducted between 2012 and 2021 and 30 pertinent papers were selected. The data from these studies show that the beta-blockers have inferior antihypertensive and stroke protective effect compared with the other classes of antihypertensive drugs and should be used as first line therapy only in patients with hypertension associated with coronary artery disease or heart failure. The information from these papers and collateral literature will be discussed in this perspective.

The pathophysiology and management of diuretic resistance in patients with heart failure.

OBJECTIVES: The objectives of the study are to investigate the causes of diuretic resistance in patients with advanced congestive heart failure (CHF), since diuretics are the cornerstone of treatment of these patients. Several studies have shown that diuretic resistance in patients with advanced CHF is common, ranging from 25% to 50% in hospitalized patients. METHODS: In order to get a current perspective as to the magnitude of diuretic resistance in such patients, a focused Medline search of the English language literature was conducted between 2015 and 2020 using the search terms, CHF, diuretics, treatment, resistance, frequency, and 30 papers with pertinent information were selected. RESULTS: The analysis of data from the selected papers demonstrated that diuretic resistance is common in hospitalized patients with advanced CHF and frequently associated with renal failure, which is secondary to CHF. CONCLUSIONS: Diuretic resistance appears to be common in patients with advanced CHF and it is mostly due to decreased cardiac output, low blood pressure, decreased glomerular filtration rate, decreased filtration of sodium, and increased tubular reabsorption of sodium. Diuretic resistance in such patients can be overcome with the combination of loop diuretics with thiazide and thiazide-like diuretics, aldosterone antagonists, as well as other agents. The data from these studies in combination with collateral literature will be discussed in this review.

Inverse Association of Poultry, Fish, and Plant Protein Consumption With the Incidence of Cardiovascular Disease.

Cardiovascular disease (CVD) remains a major cause of death and disability worldwide and food intake plays an important role in its onset or prevention. It is also well known that consumption of red meat (processed and unprocessed) is associated with an increased incidence of CVD, coronary heart disease (CHD), and premature death. However, little is known about the association of consumption of poultry, fish, and plant protein with the incidence of CVD, CHD, and mortality. Several recent studies, reviews, and meta-analyses have shown an inverse association of consumption of these foods with the incidence of CVD, CHD, and death. In order to get a better perspective about the current consumption of these foods, a focused Medline search of the English language literature was conducted between 2010 and 2020 using the terms poultry, fish, plant protein consumption, cardiovascular disease, CHD, mortality; 28 articles with pertinent information were retrieved. The analysis of data from these articles suggests an inverse relationship between the consumption of these foods and the incidence of de novo CVD or worsening of preexisting CVD. They also demonstrate that the consumption of these foods is still low and that great effort should be made to inform the public about the benefits of switching from red meat to increased consumption of poultry, fish, and plant protein. All the data from the retrieved articles regarding the consumption of these foods, together with collateral literature, will be discussed in this review.

The Debate Over Egg Consumption and Incident Cardiovascular Disease.

There is a great debate regarding the association of cholesterol intake from egg consumption and the incidence of cardiovascular disease (CVD). Most studies show that moderate egg consumption is not associated with a significant increase in CVD, stroke, heart failure, and type 2 diabetes mellitus (T2DM), whereas others dispute this fact and state that there is an association with increased egg consumption, especially if they are consumed with saturated fats. In addition, the recent relaxation of cholesterol intake to greater than 300 mg/d by the American College of Cardiology/American Heart Association Nutritional Guidelines has fueled this debate. In order to get a current perspective on the significance of moderate egg consumption with the primary incidence of CVD, a focused Medline search of the English language literature was conducted between 2010 and March 2020 using the terms, cholesterol intake, egg consumption, coronary artery disease, CVD, and T2DM. Nineteen pertinent articles were retrieved, and these, together with collateral literature, will be discussed in this review article. The analysis of data from the articles retrieved indicated that several studies showed that moderate egg consumption (1 egg/d) is not associated with adverse cardiovascular effects in subjects free of CVD or T2DM, whereas other studies showed a positive association, especially in patients with preexisting CVD or T2DM. Therefore, at present, there is no unanimous agreement on this subject, and the controversy will continue until new confirmatory evidence becomes available.

New and emerging cardiovascular and antihypertensive drugs.

INTRODUCTION: Hypertension and cardiovascular diseases (CVD) are very common conditions and account for significant medical disability and death worldwide. Therefore, their successful management is very critical for the prevention of the significant cardiovascular and socioeconomic consequences arising from their poor management. Areas Covered: Although we have several effective cardiovascular (CV) drugs for their treatment, they are not all completely successful for the effective management of CVD and hypertension. Thus, the need for the discovery and development of new drugs is necessary. For this review, a Medline search of the English language was conducted between 2010 and June 2020 and 62 pertinent papers were retrieved. These papers contain information on newly released and emerging new cardiovascular drugs. EXPERT OPINION: These new chemical entities have different mechanisms of action and in preliminary studies have been successful in the treatment of hypertension, CVD, heart failure, stroke, and type 2 diabetes mellitus. These drugs can be used either alone or in combination with other antihypertensive and cardiovascular drugs. Hopefully, these new classes of cardiovascular drugs would be effective for the treatment of hypertension and CVD and decrease their socioeconomic consequences.

Adverse cardiovascular and blood pressure effects of drug-induced hypomagnesemia.

Introduction: The objective of this study was to review the current status of drug-induced hypomagnesemia and its adverse effects on cardiovascular disease (CVD) and hypertension. Since magnesium is a potent vasodilator, which modulates vasomotor tone, peripheral blood flow, and hypertension, its deficiency could have significant cardiovascular and blood pressure (BP) effects.Areas covered: Studies have shown that several factors can contribute to magnesium deficiency including age, diet, disease, and certain drugs such as diuretics and proton-pump inhibitors (PPIs). For an updated perspective of drug-induced hypomagnesemia, a Medline search of the English language literature was conducted between 2010 and 2019 using the terms diuretics, proton-pump inhibitors, hypomagnesemia, cardiovascular disease, hypertension, and 35 pertinent papers were retrieved.Expert opinion: The data showed that magnesium deficiency is difficult to occur since it is plentiful in green leafy vegetables, cereals, nuts, and the drinking water. However, magnesium deficiency can occur with the use of diuretics for the treatment of hypertension and heart failure, or the use of PPIs for the treatment of gastroesophageal reflux disease. Therefore, magnesium deficiency should be detected and treated to prevent the aggravation of hypertension and the onset of CVD and serious cardiac arrhythmias including torsades de points.

A cardiac computed tomography first strategy to evaluate chest pain in a rural setting: outcomes and cost implications.

INTRODUCTION: Chest pain continues to be a major burden on the healthcare system with more than eight million patients being evaluated in the emergency department (ED) setting annually at a cost of greater than 10 billion dollars. Missed chest pain diagnoses for ischemia are the leading cause of malpractice lawsuits for ED physicians. The use of cardiac computed tomography angiography (CCTA) to assess acute chest pain was adopted at the Chickasaw Nation Medical Center to attempt to accurately diagnose low to intermediate risk chest pain and potentially reduce the cost of chest pain evaluation to the system while still transferring appropriate high-risk patients. PATIENTS AND METHODS: Patients presenting to the ED with low to moderate risk chest pain were evaluated with at least two negative troponin levels, an ECG, and in most instances overnight observation followed by CCTA in the morning if eligible. High-risk patients were transported to a tertiary care facility with cardiac catheterization capabilities. Medical records were checked to determine if any adverse events had occurred during follow-up. Adverse events were defined as myocardial infarction, death, and/or revascularization. Mean follow-up was 28 months. RESULTS: Of the 368 patients studied, 29 patients were transferred due to findings of at least moderate obstructive disease. Of those 29 patients transferred, 11 patients underwent revascularization (10 underwent percutaneous coronary intervention and one underwent coronary artery bypass grafting). The average coronary artery calcium score for patients transferred was 96.1. The average coronary artery calcium score for patients undergoing revascularization was 174.6. Six patients had normal coronary arteries on catheterization. The remaining 12 patients had the moderate obstructive disease by catheterization that was not physiologically significant by either invasive fractional flow reserve or in two instances, negative stress perfusion testing. At 24 months, two patients had undergone revascularization and one patient had died suddenly. CONCLUSION: The cost savings associated with a CCTA first strategy to evaluate chest pain were ~$1 200 244.10. For a self-insured health system such as the Chickasaw Nation, these are very important cost savings.

Predictive factors of discordance between the instantaneous wave-free ratio and fractional flow reserve.

OBJECTIVES: To identify clinical, angiographic and hemodynamic predictors of discordance between instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR). BACKGROUND: The iFR was found to be non-inferior to the gold-standard FFR for guiding coronary revascularization, although it is discordant with FFR in 20% of cases. A better understanding of the causes of discordance may enhance application of these indices. METHODS: Both FFR and iFR were measured in the prospective multicenter CONTRAST study. Clinical, angiographic and hemodynamic variables were compared between patients with concordant values of FFR and iFR (cutoff ≤0.80 and ≤0.89, respectively). RESULTS: Out of the 587 patients included, in 466 patients (79.4%) FFR and iFR agreed: both negative, n = 244 (41.6%), or positive, n = 222 (37.8%). Compared with FFR, iFR was negative discordant (FFR+/iFR-) in 69 (11.8%) patients and positive discordant (FFR-/iFR+) in 52 (8.9%) patients. On multivariate regression, stenosis location (left main or proximal left anterior descending) (OR: 3.30[1.68;6.47]), more severe stenosis (OR: 1.77[1.35;2.30]), younger age (OR: 0.93[0.90;0.97]), and slower heart rate (OR: 0.59[0.42;0.75]) were predictors of a negative discordant iFR. Absence of a beta-blocker (OR: 0.41[0.22;0.78]), older age (OR: 1.04[1.00;1.07]), and less severe stenosis (OR: 0.69[0.53;0.89]) were predictors of a positive discordant iFR. CONCLUSIONS: During iFR acquisition, stenosis location, stenosis degree, heart rate, age and use of beta blockers influence concordance with FFR and should be taken into account when interpreting iFR.

Obesity-related heart failure with preserved ejection fraction: new treatment strategies.

OBJECTIVES: Obesity has risen in the US and worldwide, and has become a major risk factor for type 2 diabetes mellitus (T2DM), hypertension, cardiovascular disease, and mostly HF with preserved ejection fraction (HFpEF). Also, the prevalence of HF is quite high in the US accounting for 6.6 million adults at present and is projected to reach 8.5 million by the year 2030 and is equally divided between HFpEF and heart failure reduced ejection fraction (HFrEF). Patients with HFpEF are resistant to treatment with drugs usually used for the treatment of HFrEF, but the reasons for this resistance are not clearly known. METHODS: In order to get a better perspective on the current status of the underlying pathophysiology and treatment of patients with HFpEF, a Medline search of the English language literature was conducted between 2015 and 2018 using the terms obesity, HFpEF, diabetes, treatment, SGLT2 inhibitors, and neprilysin inhibitors and 24 pertinent papers were selected. RESULTS: The review of these papers revealed that patients with HFpEF have expanded plasma volume, restricted left ventricular distension with increased end-diastolic volume and depressed natriuretic peptide levels. In this respect, drugs that cause increased diuresis and natriuresis should a reasonable choice to treat these patients. The recently FDA approved sodium-glucose cotransporter-2 (SGLT2) inhibitors for the treatment of T2DM, are a good choice, for the treatment of HFpEF, since they cause osmotic diuresis from glucose excretion and increase salt and water excretion and decrease plasma volume. In addition, they produce loss of calories leading to weight and blood pressure reduction and have shown to prevent the new onset HFpEF and decrease hospitalizations and death from this disease. CONCLUSION: The results of this analysis has shown that HFpEF has different pathophysiology from HFrEF and is difficult to treat. Drugs that block renal tubular glucose reabsorption and cause osmotic diuresis and natriuresis could be a good choice to treat patients with HFpEF alone or in combination with diuretics and other drugs.

The single use of body mass index for the obesity paradox is misleading and should be used in conjunction with other obesity indices.

Overweight and obesity in children and adults have significantly risen in the US and worldwide due to biological, environmental, and cultural drivers and account for about 2.1 billion people. In addition, obesity, even metabolically healthy, is a major risk factor for the metabolic syndrome, diabetes mellitus, dyslipidemia, and hypertension, all significant causes of cardiovascular disease (CVD), coronary heart disease (CHD) heart failure (HF) and stroke. However, despite these causative effects, overweight and obesity frequently, confer protection in patients with established CVD, CHD, HF, and hypertension, compared to normal weight persons, the so-called 'obesity paradox'. This phenomenon though is not unique, because other studies have not shown a protective effect of overweight and obesity in such patients. These controversial effects of obesity are mostly due to the use of different indices of obesity by the various studies. Most studies have used the body mass index (BMI) as an index of obesity, which is a poor index for total fat or fat distribution. In order to get a better perspective on the true nature of the obesity paradox, a Medline and Embase search of the English language literature was contacted from 2012 to 2018, using the terms, overweight, obesity, obesity paradox, CVD, HF, and hypertension. From this search, 37 pertinent papers were selected and their findings together with collateral literature will be discussed in this review. The analysis of data suggests that the existence of the obesity paradox is questionable based on the single use of BMI as a measure of obesity. The use of waist circumference and waist to hip ratio are better indices of obesity and should be used together with the BM.

Association of hypomagnesemia with cardiovascular diseases and hypertension.

OBJECTIVE: The objective of this study was to review the current evidence on the effects of Mg2+ deficiency on cardiovascular disease (CVD) and hypertension, since Mg2+ is a potent vasodilator and modulates vasomotor tone, blood pressure and peripheral blood flow. Several factors could contribute to its deficiency and when it occurs, is associated with an increased incidence of cardiovascular disease (CVD), hypertension, heart failure (HF), and cardiac arrhythmias. METHODS: In order to get a better to get an updated perspective of the current status of Mg2+ deficiency and its implications in CVD, hypertension, and cardiac arrhythmias, a focused Medline search of the English language literature was conducted between 2014 and 2018 and 30 pertinent papers were retrieved. RESULTS: The analysis of data showed that Mg2+ deficiency is difficult to occur, under normal circumstances, because it is plentiful in green leafy vegetables, cereals, nuts, and the drinking water. However, Mg2+ deficiency can occur under special circumstances such as hypertension and HF treated with large doses of diuretics, patients with chronic kidney disease (CKD) treated with hemodialysis, and patients with gastroesophageal reflux disease treated with proton pump inhibitors. When hypomagnesemia occurs, it is associated with serious cardiac arrhythmias and aggravation of hypertension. CONCLUSION: The analysis of data suggests that Mg2+ deficiency does occur and it is associated with an increased incidence of CVD, HF, serious cardiac arrhythmias, and hypertension. Retaining normal Mg2+ levels will prevent the onset of these diseases.

The current status of homocysteine as a risk factor for cardiovascular disease: a mini review.

INTRODUCTION: Hyperhomocysteinemia has been considered as a risk factor for systemic atherosclerosis, cardiovascular disease (CVD) and stroke and many epidemiologic and case-controlled studies have demonstrated its association with these complications. In addition, treatment of hyperhomocysteinemia with folic acid ± B vitamins prevents the development of atherosclerosis, CVD and strokes. However, subsequent prospective, randomized, placebo-controlled trials have not shown an association of high homocysteine levels or their lowering with treatment with the incidence of atherosclerosis, CVD or strokes, due possibly, to the fortification of flower with folic acid. Therefore, at present, there is a controversy regarding the significance of homocysteine as a risk factor for CVD and stroke and whether patients should be routinely screened for homocysteine. Areas covered: For these reasons, a focused Medline search of the English language literature was conducted between 2010 and 2017 using the terms, homocysteine, risk factor, atherosclerosis, cardiovascular disease, stroke, treatment, and 38 papers with pertinent information were selected. Expert commentary: The review of data disclosed that there is a great controversy regarding the significance of homocysteine as a risk factor for CVD and stroke. The data from these papers together with collateral literature will be discussed in this mini review.

Clinical Utility of Imaging Left Ventricular Assist Devices with 320 Row Multidetector Computed Tomography.

Evaluation of left ventricular devices is becoming increasingly important as the implantation of these devices increases. Cardiac computed tomography angiography (CCTA) has many potential advantages compared with plain radiographs and echocardiography to troubleshoot these devices and potentially help guide therapy. Heart failure (HF) remains a deadly, progressive disease with substantive and increasing morbidity, mortality, cost, and prevalence. Use of left ventricular assist devices (LVAD) as treatment for refractory HF has been steadily rising during the last decade. Seventy-four LVAD recipients who met an indication for CCTA were referred for scanning at our center for a total of 94 studies. All recipients had received a Heart Mate II (Thoratec, Pleasanton, CA) LVAD at a previous time. All patients underwent gated CCTA on a 320 row multidetector scanner (Aquilion ONE, Toshiba Medical Systems, Irvine, California, USA). Images were then reconstructed and analysis was performed using multiple oblique views. All 94 studies had technically good images. In survival analysis, 43 of the 74 LVAD patients had normal CCTA findings while 31 had abnormal CCTA results. The 6, 12, and 18 months survival was 93%, 79%, and 77% in those with normal results and 71%, 61%, and 61%, respectively, in the abnormal CCTA findings. Overall survival was statistically significant in when comparing the two groups (p = 0.003). Cardiac computed tomography angiography may be used as an aid for risk stratification and a potential indicator of short- and long-term prognosis in LVAD patients.

Cardiovascular benefits and risks of testosterone replacement therapy in older men with low testosterone.

Many studies have shown that low testosterone (T) levels have been associated with increased risk for cardiovascular (CV) events, type 2 diabetes mellitus (T2DM), and strokes. In contrast, many other studies have demonstrated that normal T levels or the normalization of low T levels with testosterone replacement therapy (TRT) is associated with decreased incidence of CV events, T2DM, and strokes, besides improving sexual function and the quality of life. However, recent studies have indicated that TRT could lead to increased incidence of CV events and strokes. These latter studies have created a great controversy among physicians regarding these findings, who question the validity of their results. In order to get a better perspective on the current status of TRT in hypogonadal men, a focused Medline and EMBASE search of the English language literature was conducted between 2010 and 2017 using the terms hypogonadism, low Testosterone, cardiovascular disease, testosterone replacement therapy, benefits, risks, older men, mechanism of action, and 58 papers with pertinent information were selected and 48 papers were rejected. The selected papers will be discussed in this review. In conclusion, based on the current status of TRT, the majority of studies indicate that TRT is safe and is associated with prevention of CVD and strokes in hypogonadal men. However, the evidence is not uniform and the therefore, decision to administer TRT should be discussed with the patient till more definitive information becomes available.

The State of the Absorb Bioresorbable Scaffold: Consensus From an Expert Panel.

Significant progress has been made in the percutaneous coronary intervention technique from the days of balloon angioplasty to modern-day metallic drug-eluting stents (DES). Although metallic stents solve a temporary problem of acute recoil following balloon angioplasty, they leave behind a permanent problem implicated in very late events (in addition to neoatherosclerosis). BRS were developed as a potential solution to this permanent problem, but the promise of these devices has been tempered by clinical trials showing increased risk of safety outcomes, both early and late. This is not too dissimilar to the challenges seen with first-generation DES in which refinement of deployment technique, prolongation of dual antiplatelet therapy, and technical iteration mitigated excess risk of very late stent thrombosis, making DES the treatment of choice for coronary artery disease. This white paper discusses the factors potentially implicated in the excess risks, including the scaffold consideration and deployment technique, and outlines patient and lesion selection, implantation technique, and dual antiplatelet therapy considerations to potentially mitigate this excess risk with the first-generation thick strut Absorb scaffold (Abbott Vascular, Abbott Park, Illinois). It remains to be seen whether these considerations together with technical iterations will ultimately close the gap between scaffolds and metal stents for short-term events while at the same time preserving options for future revascularization once the scaffold bioresorbs.

Herbs Used for the Treatment of Hypertension and their Mechanism of Action.

There is great interest lately, in the use of herbs for the treatment of hypertension and cardiovascular disease (CVD). Herbs and plants contain many phytochemicals that have been effective in the treatment of CVD and hypertension. Accumulating scientific evidence provides a reason for the use of herbs by health practitioners for treating their patients. The rationale for this expanding use of herbs is the belief of patients in a "holistic medicine" and that herbs are natural, safe, and effective. However, there are reasons of concern with the use of herbs, because they are not regulated or supervised carefully and their use could lead to serious complications or interactions with their combination with traditional medicines. In addition, their use is associated with significant out of pocket expenses, because their use is not compensated by health insurance providers. In this review, we present the scientific evidence for the use of herbs.