Reduction of Vascular Inflammation, LDL-C, or Both for the Protection from Cardiovascular Events?

Background: Low density lipoprotein cholesterol (LDL-C) and low grade arterial inflammation are key pathogenic factors for atherosclerosis and its manifestation, cardiovascular disease (CVD). Objective: In this narrative review we assessed if decreasing LDL-C levels or inflammation or both is more effective in reducing CVD events. Results: In the Scandinavian Simvastatin Survival Study (4S), all statin trials of the 90s’ and the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) the benefit came from the LDL-C reduction. In the GREak and Atorvastatin Coronary heart disease Evaluation (GREACE), the Treating to New Targets (TNT), and the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trials both mechanisms in combination produced significant benefits. In the Atorvastatin for Reduction of MYocardial Damage during Angioplasty (ARMYDA) trials and the Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS) with a human antibody targeting IL-1β with no lipid lowering effect, the reduction in arterial inflammation played the only beneficial role because there was no change in lipids levels. Conclusion: Both LDL-C and inflammation reduction are beneficial to the reduction of CVD risk. However, canakinumab is a very expensive drug that only induced a 15% reduction in CVD events, thus drastically reducing the possibility for it to be used in clinical practice. Besides, canakinumab is associated with increased infections, some fatal. A potent statin with anti-inflammatory effects is probably the best choice for the majority of those needing hypolipidaemic drug therapy

Time in Therapeutic Range, as a Determinant of All-Cause Mortality in Patients With Hypertension.

BACKGROUND: Accumulating evidence indicates that reducing systolic blood pressure (BP) tooutcomes; however, an optimal level has not yet been determined. Many population studies or post hoc analyses suggest a target systolic BP between 120 and 140 mm Hg with increased risk above and below that range. We tested the hypothesis that consistent control of systolic BP between 120 and 140 mm Hg-time in therapeutic range-is a strong determinant of all-cause mortality among US veterans. METHODS AND RESULTS: A total of 689 051 individuals from 15 Veterans Administration Medical Centers were followed over a 10-year period. Participants were classified as hypertensive, intermediate hypertensive, and normotensive according to the number of elevated BP recordings (\u3e3, 1 or 2, and none, respectively). Time within, above, or below therapeutic range (120-140 mm Hg) was considered in quartiles and related to all-cause mortality. The study population consisted of 54% hypertensive, 19.9% intermediate, and 26.1% normotensive participants; the corresponding mortality rates for the 3 groups were 11.5%, 8%, and 1.9%, respectively (P75%) to 8.9%, 15.6%, and 23.5% towards the less consistently controlled quartiles (50-75%, 25-50%, and CONCLUSIONS: An inverse and gradual association between time in therapeutic range and all-cause mortality was observed in this large veteran cohort. Consistency of BP control over time is a strong determinant of all-cause mortality, and consistency of BP control should be monitored in everyday clinical practice

Common Secondary Causes of Resistant Hypertension and Rational for Treatment

Resistant hypertension is defined as uncontrolled blood pressure despite the use of three antihypertensive drugs, including a diuretic, in optimal doses. Treatment resistance can be attributed to poor adherence to antihypertensive drugs, excessive salt intake, physician inertia, inappropriate or inadequate medication, and secondary hypertension. Drug-induced hypertension, obstructive sleep apnoea, primary aldosteronism, and chronic kidney disease represent the most common secondary causes of resistant hypertension. Several drugs can induce or exacerbate pre-existing hypertension, with non-steroidal anti-inflammatory drugs being the most common due to their wide use. Obstructive sleep apnoea and primary aldosteronism are frequently encountered in patients with resistant hypertension and require expert management. Hypertension is commonly found in patients with chronic kidney disease and is frequently resistant to treatment, while the management of renovascular hypertension remains controversial. A step-by-step approach of patients with resistant hypertension is proposed at the end of this review paper

Endothelin receptor antagonists (ERA) in hypertension and chronic kidney disease: A rose with many thorns

The discovery of endothelin created a lot of enthusiasm and paved new therapeutic avenues for the treatment of arterial hypertension. Endothelin plays a significant role in blood pressure regulation through pronounced vasoconstriction and modulation of sodium and water reabsorption in the kidneys. Endothelin receptor antagonists have been tested in many clinical trials in patients with arterial hypertension, heart failure, pulmonary arterial hypertension, systemic sclerosis, chronic kidney disease, and diabetic nephropathy. However, the results were usually disappointing, except in pulmonary hypertension and scleroderma digital ulcers. The future of ERAs for the treatment of arterial hypertension and chronic kidney disease does not seem bright, and only the combination with other classes of antihypertensive drugs might offer a way out

The effect of antihypertensive drugs on arterial stiffness and central hemodynamics: Not all fingers are made the same

Arterial stiffness and central hemodynamics attract increasing scientific interest within the hypertensive community during the last decade. Accumulating evidence indicates that aortic stiffness is a strong and independent predictor of cardiovascular events and all-cause mortality in hypertensive patients, and its predictive value extends beyond traditional risk factors. The role of central hemodynamics and augmentation index (a marker of reflected waves), remains less established and requires further investigation. Several lines of evidence indicate that antihypertensive therapy results in significant reductions of pulse wave velocity and central hemodynamics. However, beta-blockers seem to be the only exception with significant within-class differences. Conventional beta-blockers, although equally effective in reducing pulse wave velocity, seem to be less beneficial on central hemodynamics and augmentation index than the other antihypertensive drug categories, whereas the newer vasodilating beta-blockers seem to share the benefits of the other antihypertensive drugs. In conclusion, aortic stiffness seems ready for ‘prime-time’ in the management of essential hypertension, while further research is needed for central hemodynamics and augmentation index

The emergence of ambulatory measurement of arterial stiffness and central blood pressure: A promising novelty of clinical importance or just another marker?

Whereas brachial blood pressure (BP) is still considered the gold standard for the estimation of cardiovascular risk in all clinical trials and guidelines, scientific interest is shifting towards central hemodynamics and the scientific community is experiencing a whole new revolution with the emergence of novel cardiovascular markers such as the ambulatory measurement of central BP and arterial stiffness. Central BP has already started to demonstrate its superiority over peripheral BP as a better and more reliable predictor of end-organ damage in cardiovascular diseases. Furthermore, ambulatory measurement of central BP and pulse wave velocity are expected to add much more useful information towards a more integrated assessment of cardiovascular risk and profile. However, more research is required before these novel markers could be incorporated in the everyday practice of BP measurement