The current debate over treatment of subclinical hypothyroidism to prevent cardiovascular complications.

BACKGROUND: Subclinical hypothyroidism (SCH) is an asymptomatic condition associated with increased thyroid-stimulating hormone (TSH) >4 mIU/L with normal thyroxine (T4) and triidothyronine (T3) levels. It is more common in older subjects and especially in women with an overall incidence of 10%. OBJECTIVE: Because the normal TSH levels increase with age up to 7.5 mIU/L in older people, several studies have reported either no benefits whereas others have reported the benefits of treatment. These studies have caused a great debate over the treatment of SCH, especially in older subjects. Therefore, the objective of this study was to review the current evidence over this debate by reviewing the recent literature on the subject to discern whether treatment of SCH is necessary and under what circumstances. METHODS: To get a better perspective on the current debate over treatment of SCH, a focused Medline search of the English language literature was conducted from 2012 to 2019 using the terms, hypothyroidism, subclinical, dyslipidaemia, cardiovascular disease, heart failure and 38 papers with pertinent information were selected. RESULTS: The analysis of results from these papers indicated that the normal levels of TSH are increasing with the advancement of age from 4 mIU/L up to 7.5 mIU/L for patients ≥75 years of age. Also, several of reviewed studies have shown no benefits of treatment whereas, others have shown definite benefits of treatment with levothyroxine supplementation on the clinical and metabolic effects of SBH with reductions in CVD, HF and mortality. The treatment is more effective in younger persons and less so in older persons. CONCLUSIONS: Based on the overall evidence, treatment of SCH is indicated in younger persons with a TSH level >4.0 mIU/L. In older subjects, treatment should be individualised and based on the presence of symptoms, the level of TSH, and initiated at TSH levels ≥10 mIU/L and at low doses to avoid adverse cardiovascular effects from overtreatment.

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.

Usefulness of the Polypill for the Prevention of Cardiovascular Disease and Hypertension.

Cardiovascular disease (CVD) remains the leading cause of death in the developed countries and is estimated to be the leading cause of death in the developing countries by the year 2030. The cause for this rise in CVD is the increase in the major CVD risk factors (CVRFs) like hypertension, obesity, diabetes, and hyperlipidemia, which account for 80 % of all CVD deaths worldwide. In order to prevent the increase in CVD, it has been proposed to develop a low-cost polypill containing four to five generic drugs with known effectiveness in the reduction of the CVRFs. This polypill has now been tested in several recent studies for the primary and secondary prevention of CVD and stroke with fairly good results. A Medline search of the English language literature between 2011 and 2015 resulted in the identification of 15 studies with pertinent findings. These findings together with collateral literature will be discussed in this review.

Antihypertensive therapy causes erectile dysfunction.

PURPOSE OF REVIEW: Erectile dysfunction is a common sexual disorder affecting 40% of men in the United States. However, the pathophysiologic mechanism involved in the causation of erectile dysfunction is multifactorial and not well delineated. RECENT FINDINGS: Several recent studies disclose that erectile dysfunction is the result of multiple interrelated comorbid conditions that include hypertension, coronary artery disease (CAD), heart failure, and diabetes mellitus among them. In addition to comorbid conditions, certain cardiovascular and antihypertensive drugs are also involved in the development of erectile dysfunction, with the most prominent being the thiazide type diuretics, the aldosterone receptor blockers, and the ß-adrenergic receptor blockers. Also, knowledge by the patient of the drug and its action on erectile dysfunction may increase the incidence of erectile dysfunction (Hawthorn effect). Before treatment is initiated, patients should be screened for the presence of erectile dysfunction, because this condition is associated with hypertension, CAD, heart failure, diabetes mellitus, and their treatment and an appropriate treatment regimen should be selected. If that fails, the addition of phosphodiesterase 5 inhibitors to the treatment regimen is recommended. The only exception is a patient with CAD treated with organic nitrates, in which the coadministration of phosphodiesterase 5 inhibitors is strictly prohibited. SUMMARY: Knowledge of the various comorbid conditions and their treatment associated with the development of erectile dysfunction will help the caring physician to treat his patients appropriately and safely. All these aspects will be discussed in this review.

Dual renin-angiotensin-aldosterone blockade: promises and pitfalls.

Single renin-angiotensin-aldosterone system (RAAS) blockade has been shown to be effective and safe for the treatment of hypertension, coronary heart disease (CHD), heart failure (HF), diabetes, and chronic kidney disease (CKD) with proteinuria. Due to the action of RAAS blockers at various levels of the RAAS cascade, it was hypothesized that dual RAAS blockade would result in more complete inhibition of angiotensin II (Ang II) production and be more effective in blocking its detrimental cardiovascular remodeling effects. Unfortunately, several clinical trials in patients with hypertension, CHD, HF, and CKD with proteinuria have demonstrated no superiority of dual versus single RAAS blockade, but a higher incidence of adverse events. Based on these findings, dual RAAS blockade is no longer recommended for the routine treatment of various cardiovascular diseases, except diabetic nephropathy with proteinuria and HF with reduced ejection fraction. All the new information gathered from studies within the last 3 years will be presented in this review.

Triple-combination treatment with olmesartan medoxomil/amlodipine/ hydrochlorothiazide in Hispanic/Latino patients with hypertension: the TRINITY study.

OBJECTIVE(S): Evaluate efficacy/safety of olmesartan medoxomil (OM)/amlodipine (AML)/ hydrochlorothiazide (HCTZ) in Hispanic/Latino adults with hypertension. DESIGN: Randomized, double-blind, 12-week, parallel-group study followed by a 40-week open-label extension phase. SETTING: Clinical sites (317) in the United States and Puerto Rico. PATIENTS OR PARTICIPANTS: Individuals > or =18 years of age with mean seated blood pressure (BP) > or =140/100 or > or =160/90 mm Hg divided into Hispanic/Latino (369) and non-Hispanic/Latino (2122) subgroups. INTERVENTIONS: Participants were randomized to OM 40/AML 10 mg, OM 40/HCTZ 25 mg, AML 10/HCTZ 25 mg, or OM 40/AML 10/HCTZ 25 mg during the double-blind phase. During the open-label extension, all participants received OM 40/AML 5/HCTZ 12.5 mg; participants not reaching BP goal within 2 weeks were randomly titrated to OM 40/AML 10/HCTZ 12.5 mg or OM 40/AML 5/HCTZ 25 mg, then to OM 40/AML 10/ HCTZ 25 mg after another 2 weeks. MAIN OUTCOME MEASURE: Change in mean seated diastolic BP (SeDBP) from baseline (double-blind phase). RESULTS: Triple-drug therapy vs the dual therapies resulted in greater mean reduction in SeBP (Hispanic/Latino: 35.0/20.9 mm Hg vs 27.8-30.9/15.3-17.7 mm Hg; non-Hispanic/Latino: 39.0/21.7 mm Hg vs 28.9-31.5/14.6-17.8 mm Hg) and enabled more participants to reach BP goal (Hispanic/Latino: 56.8% vs 40.6%-51.2%; non-Hispanic/Latino: 65.7% vs 33.8%-46.6%) irrespective of ethnicity. The efficacy of triple-drug therapy in achieving BP goal was sustained long-term (40-week open-label extension period) in Hispanic/Latino (63.3%) and non-Hispanic/ Latino (64.2%) participants. Triple-drug therapy was well tolerated in Hispanic/Latino and non-Hispanic/Latino participants. CONCLUSIONS: In this study, OM/AML/HCTZ was an effective treatment option in Hispanic/ Latino patients with hypertension.

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 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.

Effectiveness and safety of phosphodiesterase 5 inhibitors in patients with cardiovascular disease and hypertension.

Phosphodiesterase 5 (PDE 5) inhibitors are selective inhibitors of the enzyme PDE 5, which catalyzes the hydrolysis of cyclic guanosine monophosphate (cGMP), a potent vasodilator and nitric oxide (NO) donor, to its corresponding metabolites (monophosphates). The enzyme PDE 5 is widely distributed in the body, including the heart and blood vessels. Because of its distribution, it was hypothesized that its inhibition could lead to significant coronary vasodilation, which would benefit patients with coronary artery disease (CAD). This hypothesis led to the development of PDE 5 inhibitors with the first being sildenafil citrate. Subsequent studies with sildenafil in patients with CAD demonstrated a modest cardiovascular effect, but a potent action on penile erection in men, resulting in sildenafil becoming a first-line therapy of erectile dysfunction (ED). Subsequently, two more PDE 5 inhibitors (vardenafil and tadalafil) were developed and approved by the Food and Drug Administration (FDA) for the treatment of ED. Recent studies have shown several pleiotropic beneficial effects of PDE 5 inhibitors in patients with CAD, hypertension, heart failure, pulmonary arterial hypertension, diabetes mellitus and Raynaud's phenomenon. Side effects and interactions of PDE 5 inhibitors with other drugs have been minimal, with the exception of their coadministration with nitrates, which could lead to severe vasodilation and hypotension and therefore, their coadministration is prohibited. All these pleiotropic cardiovascular effects of PDE 5 inhibitors and their drug interactions will be discussed in this concise review in the context of the American College of Cardiology / American Heart Association guidelines and the recent developments in this field.

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.

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.

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.

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.

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 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.

Olmesartan/amlodipine/hydrochlorothiazide in participants with hypertension and diabetes, chronic kidney disease, or chronic cardiovascular disease: a subanalysis of the multicenter, randomized, double-blind, parallel-group TRINITY study.

BACKGROUND: Patients with hypertension and cardiovascular disease (CVD), diabetes, or chronic kidney disease (CKD) usually require two or more antihypertensive agents to achieve blood pressure (BP) goals. METHODS: The efficacy/safety of olmesartan (OM) 40 mg, amlodipine besylate (AML) 10 mg, and hydrochlorothiazide (HCTZ) 25 mg versus the component dual-combinations (OM 40/AML 10 mg, OM 40/HCTZ 25 mg, and AML 10/HCTZ 25 mg) was evaluated in participants with diabetes, CKD, or chronic CVD in the Triple Therapy with Olmesartan Medoxomil, Amlodipine, and Hydrochlorothiazide in Hypertensive Patients Study (TRINITY). The primary efficacy end point was least squares (LS) mean reduction from baseline in seated diastolic BP (SeDBP) at week 12. Secondary end points included LS mean reduction in SeSBP and proportion of participants achieving BP goal (<130/80 mm Hg) at week 12 (double-blind randomized period), and LS mean reduction in SeBP and BP goal achievement at week 52/early termination (open-label period). RESULTS: At week 12, OM 40/AML 10/HCTZ 25 mg resulted in significantly greater SeBP reductions in participants with diabetes (-37.9/22.0 mm Hg vs -28.0/17.6 mm Hg for OM 40/AML 10 mg, -26.4/14.7 mm Hg for OM 40/HCTZ 25 mg, and -27.6/14.8 mm Hg for AML 10/HCTZ 25 mg), CKD (-44.3/25.5 mm Hg vs -39.5/23.8 mm Hg for OM 40/AML 10 mg, -25.3/17.0 mm Hg for OM 40/HCTZ 25 mg, and -33.4/20.6 mm Hg for AML 10/HCTZ 25 mg), and chronic CVD (-37.8/20.6 mm Hg vs -31.7/18.2 mm Hg for OM 40/AML 10 mg, -30.9/17.1 mm Hg for OM 40/HCTZ 25 mg, and -27.5/16.1 mm Hg for AML 10/HCTZ 25 mg) (P<0.05 for all subgroups vs dual-component treatments). BP goal achievement was greater for participants receiving triple-combination treatment compared with the dual-combination treatments, and was achieved in 41.1%, 55.0%, and 38.9% of participants with diabetes, CKD, and chronic CVD on OM 40/AML 10/HCTZ 25 mg, respectively. At week 52, there was sustained BP lowering with the OM/AML/HCTZ regimen. Overall, the triple combination was well tolerated. CONCLUSIONS: In patients with diabetes, CKD, or chronic CVD, short-term (12 weeks) and long-term treatment with OM 40/AML 10/HCTZ 25 mg was well tolerated, lowered BP more effectively, and enabled more participants to reach BP goal than the corresponding 2-component regimens. TRIAL IDENTIFICATION NUMBER: NCT00649389.

The role of angiotensin II receptors in stroke protection.

The hypothesis that angiotensin II (Ang II) might have a stroke-protective role was first proposed by Brown and Brown about 25 years ago. Their hypothesis was generated from the results of the first Medical Research Council trial in patients with mild to moderate hypertension, which showed that patients treated with the diuretic bendrofluazide had a 70% decrease in strokes compared with those treated with the ß-blocker propranolol for similar blood pressure reduction. This hypothesis, which remained dormant for many years, was recently resurrected by several experimental studies that showed that the brain possesses its own renin-angiotensin system (RAS) similar to the one existing in the systemic circulation. These studies also showed that the brain RAS plays an important role in stroke prevention and neuronal protection through its active peptide Ang II. In addition, these studies demonstrated that the beneficial effects of Ang II are mediated through stimulation of its subtype 2 receptors, and possibly through stimulation of the subtype 4 receptors by Ang IV, a metabolite of Ang II. Drugs that selectively block the Ang II subtype 1 receptors, such as the angiotensin receptor blockers, have shown superior protection against strokes and neuronal damage than drugs that decrease the generation of Ang II, such as the angiotensin-converting enzyme inhibitors and ß-blockers. In this review, the role of the Ang II receptors and their mechanism of action regarding stroke prevention are discussed in view of the evidence from experimental and clinical studies.

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.

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.