The role of gut microbiota in the development of salt-sensitive hypertension and the possible preventive effect of exercise.

INTRODUCTION: The aim of the present study is to analyze the data indicating an association between high salt intake and the gastrointestinal microbiota in the development of salt-sensitive hypertension in animals and men. It is also, to discuss the preventive effects of exercise on gut-induced hypertension by favorably modifying the composition of gut microbiota. AREAS COVERED: Salt sensitivity is quite common, accounting for 30%-60% in hypertensive subjects. Recently, a novel cause for salt-sensitive hypertension has been discovered through the action of gut microbiota by the secretion of several hormones and the action of short chain fatty acids (SCFAs). In addition, recent studies indicate that exercise might favorably modify the adverse effects of gut microbiota regarding their effects on BP. To identify the role of gut microbiota on the incidence of hypertension and CVD and the beneficial effect of exercise, a Medline search of the English literature was conducted between 2018 and 2023 and 42 pertinent papers were selected. EXPERT OPINION: The analysis of data from the selected papers disclosed that the gut microbiota contribute significantly to the development of salt-sensitive hypertension and that exercise modifies their gut composition and ameliorates their adverse effects on BP.

The Option of Chronotherapy of Hypertension.

The aim of the present paper is to explore the option of chronotherapy of hypertension and its effectiveness in blood pressure (BP) lowering compared with its standard daily treatment. The treatment of BP has gone through many different schemes over the years. From no treatment in the early 1930s, to step care, to multiple drug combinations, or to single daily drug combinations with 2-3 drugs, still BP is not well controlled in a significant number of patients. Recently, the role of the circadian rhythm in the treatment of hypertension has been tested by several studies comparing the evening versus the morning drug administration with no clear evidence of superiority of either mode of drug administration. However, in cases of morning surge of BP, nocturnal hypertension, and renal disease, the evening drug administration has been more effective than the morning drug administration, and thus, more preferable. In order to get a better perspective on this approach of hypertension treatment, a Medline search of the English literature was contacted between 2010 and 2023 using the terms BP control, circadian rhythm, morning drug administration, evening drug administration, and 38 pertinent papers were selected for analysis. Careful review of the selected papers showed that chronotherapy of hypertension is effective. However, the overall effectiveness of evening drug administration compared with the morning administration is not significantly more effective compared to the morning administration and more work is needed in this field.

Effects of physical activity on sleep quality and wellbeing.

Physical activity (PA) has pluripotential beneficial effects on body functions. These benefits include reduction in the incidence of cardiovascular disease (CVD), coronary heart disease (CHD), hypertension, type 2 diabetes mellitus (T2DM), and death. In addition to these effects, PA exerts significant beneficial effects on sleep onset, duration and quality, which add to its beneficial effects. In contrast, lack of sleep has been associated with increased incidence of CVD complications and death. In this regard, PA serves as a non-pharmacologic means for sleep improvement especially in older people, who frequently have difficulties in falling asleep. Regarding the timing of exercise and its effect on sleep, there has been no difference between morning and evening exercise on the onset and quality of sleep. With respect the beneficial cardiovascular effects of PA on sleep, there has been a debate among several investigators with some reporting significant beneficial effects of PA, and others reporting not significant beneficial effects. In order to get a better perspective on the effects of PA on quality of sleep, and its cardiovascular beneficial effects, a Medline search of the English literature was conducted between 2017 and 2023 using the terms exercise, sleep, cardiovascular disease, death and 36 pertinent papers were selected (Figure 1). The findings from these papers together with collateral literature will be discussed in this review.

The Interaction of Kidneys and Gut in Development of Salt-Sensitive Hypertension.

The incidence of salt-sensitive hypertension is quite common and varies between 30-60% in hypertensive patients. Regarding the causal role of high salt intake in the development of salt-sensitive hypertension, recent evidence has demonstrated that the gut through its microbiota plays a significant role in its genesis. Besides the gut, the kidneys also play important role in salt-sensitive hypertension and there is clinical and experimental evidence of an interrelationship between the gut and the kidneys in the development of salt-sensitive hypertension through the so-called "gastro-renal axis." The gut besides being an absorptive organ, it is also a hormonal secretory organ involving the secretion of gastrin, dopamine, norepinephrine, angiotensin, and aldosterone which through their action with the kidneys are involved in the development of salt-sensitive hypertension. In addition, the kidneys exert a protective role against the development of hypertension through the secretion of prostaglandins and their vasodilatory action. To assess the current evidence on the role of high salt intake and the interplay of the gut and kidneys in its development, a Medline search of the English literature was contacted between 2012 and 2022, and 46 pertinent papers were selected. These papers together with collateral literature will be discussed in this review.

Possible cardiovascular risks of white coat hypertension: updated.

White-coat hypertension (WCH) has been defined as an increased blood pressure (BP) in the doctor's office and a normal BP outside the office by 24 hr ambulatory BP monitoring (ABPM) or home BP measurement. It is generated by fear and anxiety of whether an abnormal value could be found and indicate the existence of hypertension. When first described, it was defined as a neuro-defense reaction related to the presence of the doctor in their office or clinic and associated with an increase in heart rate. Initially it was considered a benign condition, not associated with the hypertension mediated organ damage (HMOD) and not requiring treatment. However, recent studies have shown that WCH is not a benign condition and is associated with HMOD and cardiovascular (CV) events (CVE). According to recent ACC/AHA guidelines, the outside of office normal BP should be < 130/80 mmHg and according to the ESC/ESH guidelines, the outside of office normal BP should be < 135/85 mmHg. The prevalence of WCH varies by different studies from 15% to 40% and up to 50% in older subjects. Currently, the management of WCH if not associated with CV risk factors should be conservative with healthy lifestyle changes and exercise. Drug therapy should be considered if these measures do not work or in the presence of CV risk factors, HMOD, or preexisting cardiovascular disease.

Superior stroke prevention with angiotensin receptor blockers compared with other antihypertensive drugs.

INTRODUCTION: Stroke is a major cause of death and disability and its incidence is linearly increased with the elevation of blood pressure (BP) and the advancement of age in both men and women, with its incidence being higher in older subjects, the blacks and women. AREAS COVERED: The annual worldwide incidence of stroke is 7.6 million for subjects ≥ 20 years of age with the average direct and indirect annual costs of stroke care, is expected to be $94.3 billion between 2014 and 2015. With respect to the cause of stroke, this is multifactorial, due to atherosclerotic heart disease, inflammation, atrial fibrillation, and hypertension with the latter being the most important cause. Therefore, control of BP is the major factor for its prevention. In order to get a better perspective on the current management of stroke, a Medline search of the English literature was conducted between 2014 and 2022 and 26 pertinent papers were selected. EXPERT OPINION: Review of data from the selected papers demonstrated that control of SSBP < 130 mmHg was better in stroke prevention than SBP 130-140 mmHg for primary and secondary strokes. Among the drugs used, angiotensin receptor blockers provided superior stroke prevention compared to angiotensin converting enzyme inhibitors and other antihypertensive drugs.

Association of hyperuricemia with cardiovascular diseases: current evidence.

The aim of the present study is to present a historical and unified perspective on the association of serum uric acid (SUA) in the cause of cardiovascular diseases (CVDs). The association of hyperuricemia (HUC) with CVD begun to be appreciated in the middle 1950s and early 1990s when clinical evidence was shown on the association of HUC with CVD. However, this association was disputed by several investigators including the Framingham group and by professional societies, like the American Heart Association and the American Society of Hypertension. This dispute was weakened or reversed by later studies, which showed a positive association of HUC with CVD, CHD, HF, CKD, and stroke, mediated by several risk factors, both molecular such as, oxidative stress, inflammatory stress, insulin resistance, and endothelial dysfunction, as well as clinical factors such as, atherosclerosis, hypertension, metabolic syndrome, and type 2 diabetes mellitus. The great majority of recent studies show a positive association of HUC with CVDs, and CKD. However, the cutoff of the damaging levels of SUA have not been established as yet. The European Society of Hypertension (ESH) Treatment Guidelines have proposed a cutoff level of SUA for CVD > 7 mg/dl for men and > 6 mg/dl for women. In contrast, the URRAH study has shown a SUA level of 4.7 mg/dl for all-cause mortality and 5.6 mg/dl for CV mortality. These levels are lower than the SUA levels proposed by the ESH, which are consistent with HUC. For a better understanding of this association, a Medline search of the English literature was conducted between 2015 and 2022 and 44 pertinent papers were selected. These papers together with collateral literature will be discussed in this review.

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.

The debate over the optimal blood pressure treatment target of less than 130/80 mmHg.

OBJECTIVES: The objective of this study was to analyze the controversy regarding the optimal blood pressure (BP) target of <130/80 mmHg as proposed by the 2017 American College of Cardiology/American Heart Association (ACC/AHA) across all age groups. Hypertension is a major risk factor for cardiovascular disease (CVD), stroke, and chronic kidney disease (CKD), and its optimal control is associated with lessening or preventing these complications. A recent study has argued that this BP level is universally accepted as an optimal and safe BP level. However, this argument is not accepted by other investigators, arguing that higher BP levels are as effective and safe. METHODS: In order to investigate the current status of this level of BP control, a Medline search of the English literature was conducted between 2017 and February 2022, and 25 pertinent papers were selected. RESULTS: The analysis of data from these studies indicates that these BP are effective in lowering the BP and preventing cardiovascular disease, heart failure, and chronic kidney disease, and they are indeed universally accepted. CONCLUSION: Based on the current evidence, the current proposed by the 2017 ACC/AHA treatment guidelines are effective in lowering the BP and decreasing its cardiovascular complications and should followed, till perhaps, new data come out to the contrary.

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.

A novel approach for the treatment of hypertension with the soluble guanylate cyclase stimulating drug.

INTRODUCTION: Despite the significant progress in the development of safe and effective antihypertensive drugs, the control of blood pressure (BP) is still not satisfactory. The current antihypertensive drugs reduce the BP by increasing sodium and water excretion (diuretics), by blocking the action of the sympathetic system, by blocking the calcium entry into vascular smooth muscle cells, or by blocking the action of the renin-angiotensin-aldosterone system. AREAS COVERED: There is a need for the development of new antihypertensive drugs with a different mechanism of action. This new class of drugs are the soluble guanylate cyclase (sGC) stimulators and decrease the BP through arterial vasodilation by stimulating the sGC and increasing the production of cyclic-guanosine-monophosphate (cGMP), a potent vasodilator, independently of the endogenous nitric oxide. However, there is limited research on their antihypertensive action. For further knowledge of the antihypertensive effects and safety of these drugs, a focused Medline search of the English language literature was conducted between 2010 and 2020 and 27 studies with pertinent information were selected. EXPERT OPINION: The analysis of data from these demonstrated that these drugs are safe and have beneficial antihypertensive and metabolic effects and they will be useful for hypertensive patients with diabetes and dyslipidemia.

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.

The clinical significance of isolated diastolic hypertension.

The prevalence of isolated diastolic hypertension (IDH) has been increased in hypertensive subjects with the new 2017 ACC/AHA blood pressure treatment guidelines to 6.5% from 1.3% by the JNC-7 guidelines. However, its clinical significance as a cause of adverse cardiovascular (CV) events especially in older subjects has been debated by several investigators, who have demonstrated no adverse CV effects of untreated IDH, but not by others. It is also more common in the young subjects who are at low CV risk and quite rare in the older subjects, who are at increased CV risk. Treatment of IDH in the older subjects could increase the CV complications due to a J-curve effect and, in addition, could increase the incidence of stroke from further lowering the normal systolic blood pressure (SBP). Very low SBP and DBP cannot be sustained by the cerebral blood flow autoregulation and could lead to cerebral ischemia. In order to get a better perspective of the current status of the treatment of IDH, a review of the English language literature of the available studies was conducted and 12 papers with pertinent information were retrieved. The analysis of results from these studies suggests that IDH is associated with adverse CV events in younger persons and it should be treated. In contrast, the prevalence of IDH is low in older subjects and is not associated with adverse CV events in the majority of cases. Thus, its further lowering should be avoided to prevent further decrease in normal SBP and prevent the onset of adverse CV events. However, the decision to treat IDH in older subjects should be individualized.

Noninvasive vascular function tests for the future prediction of primary cardiovascular diseases.

OBJECTIVES: Cardiovascular diseases (CVDs) still remain the main causes of death and disability in the US and worldwide, and the prediction for their future incidence is not well established. The utilization of the new cardiovascular risk score (CVRS) developed by the new ACC/AHA blood pressure treatment guidelines has improved the 10-year prediction of CVDs. However, its predictive value could be further increased with the addition of other risk factors identified with the use of several noninvasive vascular tests. These tests include, the older tests such as flow-mediated dilation (FMD), pulse wave velocity (PWV), pulse pressure (PP), and the newly developed noninvasive vascular tests of, reactive hyperemia-peripheral arterial tonometry (RH-PAT), cardio-ankle vascular index (CAVI), and the inter-arm/inter-leg pressure difference (IAPD/ILPD). METHODS: In order to get a current perspective regarding the usefulness of these new noninvasive vascular tests for the future prediction of CVDs, a Medline search of the English language literature was conducted between 2014 and 2019 using the terms cardiovascular disease, coronary heart disease, noninvasive vascular tests, risk factors, and 26 pertinent papers were retrieved. RESULTS: The analysis of results from these papers showed that these noninvasive vascular tests have an independent predictive value for the future incidence of CVDs and hypertension. However, their long-term predictive value is not well established, since there are no currently, available data from long-term clinical outcome studies. CONCLUSION: The analysis of data from the retrieved papers demonstrated that the new noninvasive vascular tests have an independent predictive value for the future incidence of CVDs and hypertension. However, their long-term predictive value is not established as yet for the lack of long-term outcome studies. When the currently ongoing long-term trials are completed, it is quite possible that the data from these tests added to CVRS could enhance its predictive value.