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Introduction: Osteoarthritis constitutes one of the leading causes of pain and disability worldwide with a significant impact on health-care costs. Patients with osteoarthritis are often affected by a number of cardiovascular comorbidities, including hypertension, which is present in about 40% of cases. Just recently, a single tablet combination of amlodipine besylate, a calcium channel blocker, and celecoxib, a nonsteroidal anti-inflammatory drug, indicated for patients for whom treatment with amlodipine for hypertension and celecoxib for osteoarthritis are appropriate, has been recently approved. Areas covered: We reviewed data from clinical studies that investigated safety and efficacy of the combination of amlodipine and celecoxib in hypertensive patients with osteoarthritis published before 31 August 2018. The literature search was conducted using research Methodology Filters. Expert commentary: The advantages of this single formulation over sequential administration include increased compliance, possibly reduced cost, and less likelihood of dosage-related issues. Moreover, this single tablet formulation combines the anti-inflammatory activity of the celecoxib with the systemic vasodilatation induced by the amlodipine. It is a promising treatment for patients with osteoarthritis and hypertension. Nevertheless, celecoxib may cause a variable degree of blood pressure increase and only a small clinical trial has been conducted before approval to assess interactions related to blood pressure effect between these two molecules.

Introduction: Choosing between different non-vitamin K antagonist oral anticoagulants (NOACs) in non-valvular atrial fibrillation (NVAF) is difficult due to the absence of head to head comparative studies. We performed a Bayesian meta-analysis to explore similarities and differences between different NOACs and to rank treatments overall for safety and efficacy outcomes., Areas Covered: Through a systematic literature search we identified randomized controlled Phase III trials of dabigatran, rivaroxaban, apixaban, and edoxaban versus adjusted-dose warfarin in patients with NVAF., Expert Opinion: Warfarin ranked worst for all-cause mortality and intracranial bleedings and had a nil probability of ranking first for any outcome. The risk of major bleeding versus warfarin was lower with apixaban, dabigatran 110 mg, and both doses of edoxaban. All agents reduced the risk of intracranial bleeding versus warfarin. Edoxaban 30 mg was the best among the treatments being compared for major and gastrointestinal bleeding. Dabigatran 150 mg was the best for stroke and systemic embolism. This study suggests that NOACs are generally preferable to warfarin in patients with NVAF. However, safety and efficacy differences do exist among NOACs, which might drive their use in specific subsets of AF patients, allowing prescribers to tailor treatment to distinct patient profiles.

Accurate blood pressure (BP) measurement is essential for the diagnosis, monitoring and management of hypertension. However, conventional office-based BP readings have several limitations that include a low reproducibility, the white-coat effect and the existence of masked hypertension. These limitations can be addressed through the use of ambulatory BP monitoring. Because ambulatory monitoring provides measurements at specific time intervals throughout a 24-hour period, this technique represents a better picture of the normal fluctuations in BP levels associated with daily activities and sleep. In addition, end-organ damage associated with hypertension is more closely related to ambulatory BP than office BP measurements and ambulatory BP profile give better prediction of clinical outcome than conventional BP measurements.

In the ACCORD clinical trial, lowering blood pressure (BP) to normal levels, below currently recommended levels, did not significantly reduce the combined risk of fatal or nonfatal cardiovascular (CV) disease events in adults with Type 2 diabetes. A new post hoc analysis of the same trial also suggests that lowering BP in centrally obese diabetic patients is not a useful means for CV prevention. The authors discuss these findings in the light of accumulated evidence on the relationship between the degree of BP reduction and the risk of CV events in patients with diabetes. In particular, the authors focus on trial and systematic review findings, suggesting that a more intensive reduction of BP in Type 2 diabetes effectively protects from stroke.

Introduction: Aliskiren is the first orally active direct renin inhibitor approved for the treatment of hypertension. Aliskiren's inhibitory effect on angiotensin I generation, through renin blockade, is highly specific and long-lasting (24 hours). This feature differentiates aliskiren from traditional antihypertensive drugs., Areas Covered: This paper reviews the results of various clinical trials which investigate the safety and efficacy of aliskiren on blood pressure (BP) reduction and clinical end points., Expert Opinion: Aliskiren is suitable for once-daily administration. Its antihypertensive effect is comparable or superior to that of other antihypertensive agents at recommended doses. The tolerability profile of aliskiren is placebo-like at the licensed doses of 150 and 300 mg. In particular, the discontinuation of therapy due to clinical adverse events occurs similarly among patients treated with either aliskiren or placebo. Aliskiren is not recommended in association with ACE-inhibitors or angiotensin II receptor blockers in patients with type 2 diabetes and renal impairment. Pending disclosure of full results, the early termination of the ALTITUDE seems to confirm previous concerns about the safety of the dual pharmacological blockade of the renin-angiotensin system in these patients. Aliskiren is a well-tolerated antihypertensive drug that may help to achieve the recommended targets of BP control.

Cardiovascular disease (CVD) poses a significant healthcare and economic burden on societies and individuals. Angiotensin II is a key component of the renin-angiotensin system that plays a central role in atherosclerotic mechanisms that contribute to CVD. Renin-angiotensin system blockers are widely used to reduce cardiovascular (CV) risk owing to their potential both to lower blood pressure, a CV risk factor, and to attenuate the atherosclerotic disease process directly. Telmisartan has a number of pharmacological properties that distinguish it from other angiotensin II receptor blockers (ARBs) - the longest plasma half-life, highest lipophilicity and strongest receptor binding affinity in class. The ONTARGET(®) trial showed that telmisartan is as effective as ramipril in reducing CV morbidity (including myocardial infarction and stroke) and mortality in a broad range of patients at increased CV risk. Evidence from other ARBs remains largely restricted to patients with heart failure, diabetic nephropathy or specific subsets of hypertensive patients. Telmisartan is, therefore, the only ARB with a broad indication for CV risk reduction in patients with atherothrombotic disease or diabetes with end-organ damage.

Diabetes causes approximately 2.9 million deaths yearly, mainly through an increased risk of cardiovascular disease. In hypertensive diabetics, blood pressure reduction determines a significantly lower rate of cardiovascular and renal events. Conversely, reaching the generally recommended target of lower than 130/80 mmHg is a difficult challenge and, in most cases, two or more antihypertensive drugs are required. Until recently, there was a general consensus that combination treatment should include a diuretic as one of the two fundamental agents. However, recently published trials using calcium channel blockers plus renin-angiotensin system-blocking agents showed that such a combination reduces the risk of major cardiovascular events, provides greater renoprotection, and improves metabolic outcomes as compared with diuretic-based combinations. The present review explores the potential for an 'optimal' combination therapy in patients with diabetes mellitus and hypertension, in view of recent experimental and clinical evidence.

Background: To evaluate distribution and prognostic value of total cholesterol and lipoprotein fractions in essential hypertension., Methods: In a prospective cohort study, 2649 initially untreated subjects with essential hypertension (aged 51, 46.5% women) were investigated at entry and followed for a mean of 5.6 years (range: 1-16)., Results: At entry, subjects with total cholesterol (TC) > or =240 mg/dl (> or =6.22 mmol/l) or high-density lipoprotein (HDL) cholesterol (HDL-C) <40 mg/dl (1.05 mmol/l) or low-density lipoprotein (LDL) cholesterol (LDL-C) > or =160 mg/dl (4.13 mmol/l) or TC/HDL-C ratio >6 were 47.7%. TC, HDL-C, LDL-C and triglycerides (TG) did not show any association with office or 24-h ambulatory blood pressure (BP). During follow-up there were 167 first cardiac events and 122 first cerebrovascular events. TC, HDL-C, LDL-C and TC/HDL-C ratio showed an association with cardiac events, but not with cerebrovascular events. TG did not show any association with cardiac or cerebrovascular events. After adjustment for age, sex, diabetes, smoking, left ventricular (LV) hypertrophy and 24-h pulse pressure, the hazard ratio for cardiac events was 1.83 (95% CI 1.23-2.71) in association with a TC > or =6.22 mmol/l, 2.23 with a HDL-C <1.05 mmol/l (95% CI 1.06-4.70), 2.83 with a LDL-C > or =4.91 mmol/l (95% CI 1.48-5.42) and 3.90 with a TC/HDL-C ratio >6.0 (95% CI 2.23-6.81). When forced in the same model, HDL-C and LDL-C showed an independent association with cardiac events., Conclusions: Abnormalities of TC and lipoproteins are common in essential hypertension. HDL-C and LDL-C independently predict the risk of cardiac, but not cerebrovascular, events. Their predictive value is independent of several confounding factors including LV hypertrophy and ambulatory BP.

We administered ethanol to pregnant rats and determined cholesterol, lipid phosphorus and fluorescence anisotropy of diphenylhexatriene (DPH) and of trimethylaminophenyl hexatriene (TMA-DPH) in erythrocyte ghosts of newborn pups and of their mothers. Cholesterol content was different in dams and pups and changed after treatment. Age, but not ethanol, affected lipid phosphorus. Either age (dams versus pups) or treatment affected the curves of DPH fluorescence anisotropy (r) versus temperature (T), but those of TMA-DPH did not change, indicating that only the inner core of the membrane was influenced. We conclude that adult and erythrocyte ghosts differed for the lipid composition, for the dependence of r on T (for DPH) and for the effects of ethanol dosing on these parameters.