“Cardiac dysfunction is associated with neuroanatomic and neuropsychological changes in aging adults with prevalent cardiovascular disease, theoretically because systemic hypoperfusion disrupts cerebral perfusion, contributing to subclinical brain injury.“

They set out to test whether the cardiac index (the amount of blood the heart pumps in proportion to body size) as a metric for cardiac function would correlate with loss of brain tissue as shown by brain MRI and neuropsychological markers of ischemia (reduction of oxygen due reduced blood flow) and Alzheimer’s disease. What did the data show?

“…cardiac index was positively related to total brain volume and information processing speed and inversely related to lateral ventricular volume…participants in the bottom cardiac index tertile and middle cardiac index tertile had significantly lower brain volumes than participants in the top cardiac index tertile.”

Even the people with the middle cardiac group (low normal) had showed signs of serious neurodegeneration with brain atrophy (lower brain volume). How important is it to get better than a low normal amount of blood to the brain?

“Although observational data cannot establish causality, our findings are consistent with the hypothesis that decreasing cardiac function, even at normal cardiac index levels, is associated with accelerated brain aging.“

Consider this in light of earlier research that aggressive treatment of blood pressure is harmful. Clinicians must respect the need to balance cardiovascular protection from excessive pressure dynamics with the profound need to ensure adequate cerebral perfusion. Are you concerned that your blood pressure therapy may be stronger than it should? Read the earlier research posts and discuss the matter with your doctor.

“Experimental studies implicate the renin-angiotensin system, particularly angiotensin II type-1 and type-2 receptors, in the regulation of cell proliferation, angiogenesis, and tumour progression. We assessed whether ARBs affect cancer occurrence with a meta-analysis of randomised controlled trials of these drugs.”

They analyzed data from a number of trials involving tens of thousands of patients and came to this conclusion:

“This meta-analysis of randomised controlled trials suggests that ARBs are associated with a modestly increased risk of new cancer diagnosis.”

An accompanying editorial in the same issue expresses the gravity of this matter:

“The meta-analysis…is disturbing and provocative, raising crucial drug safety questions for practitioners and the regulatory community.”

Why use this class of medications when there is no evidence that they are more effective than others? A functional approach obviating the need for side-effect producing drugs is often successful if instituted early enough. While research data continues to accumulate about ARBs the author exhorts us to take this finding into serious and cautious consideration when determining the best approach to blood pressure for each person:

“In the interim, we should use ARBs, particularly telmisartan, with greater caution. These drugs are often overprescribed, as a result of aggressive marketing and in the absence of evidence that they are better than angiotensin-converting enzyme (ACE) inhibitors.”

“Here we report that chronic TRPV1 activation by dietary capsaicin increases the phosphorylation of protein kinase A (PKA) and eNOS and thus production of nitric oxide (NO) in endothelial cells…Long-term stimulation of TRPV1…improves vasorelaxation, and lowers blood pressure in genetically hypertensive rats. We conclude that TRPV1 activation by dietary capsaicin improves endothelial function. TRPV1-mediated increase in NO production may represent a promising target for therapeutic intervention of hypertension.”

The endothelium is the inner lining of the blood vessel; good endothelial function is necessary for cardiovascular health. (Viagra and similar medications work by inhibiting the breakdown of nitric oxide, a vasodilator.) An accompanying editorial in the same journal notes that the authors:

“…demonstrate that vascular TRPV1 mediates a beneficial effect of capsaicin in the cardiovascular system, promoting nitric oxide release and lowering blood pressure.”

An editorial in Science Signaling also recognizes this research:

The chemical in chili peppers that makes them taste hot is called capsaicin, and it activates a cation channel of the transient receptor potential family called TRPV1…Now Yang et al. provide evidence that dietary capsaicin may reduce blood pressure if made a constant part of the diet…Additionally, 6-month dietary consumption of capsaicin increased the relaxation response of isolated mouse mesenteric arteries to acetylcholine…How much of capsaicin’s effects on blood pressure are due to a direct effect on the vasculature and how much are mediated through effects on the nervous system remains to be determined, but these results suggest that targeting TRPV1 may be beneficial for the treatment of hypertension.

“…determine the association of systolic BP control achieved and adverse cardiovascular outcomes in a cohort of patients with diabetes and CAD (coronary artery disease).”

They analyzed data for 6400 subjects from 862 sites in 14 countries for more than ten years.

“Patients received first-line treatment of either a calcium antagonist or β-blocker followed by angiotensin-converting enzyme inhibitor, a diuretic, or both to achieve systolic BP of less than 130 and diastolic BP of less than 85 mm Hg. Patients were categorized as having tight control if they could maintain their systolic BP at less than 130 mm Hg; usual control if it ranged from 130 mm Hg to less than 140 mm Hg; and uncontrolled if it was 140 mm Hg or higher.”

The data they accumulated painted this picture:

“…little difference existed between those with usual control and those with tight control…The all-cause mortality rate was 11.0% in the tight-control group vs 10.2% in the usual-control group; however, when extended follow-up was included, risk of all-cause mortality was 22.8% in the tight control vs 21.8% in the usual control group.”

Note that the tight control group had a slightly higher risk of all-cause mortality over the longer time period. Besides the greater likelihood of adverse effects with higher doses of medication, lower blood pressure means diminished delivery of oxygen to tissues (the pressure acts to overcome the increased resistance of less a healthy circulatory system).

Their conclusion clearly states the lack of benefit with suppression to less than 130 mm Hg:

“Tight control of systolic BP among patients with diabetes and CAD was not associated with improved cardiovascular outcomes compared with usual control.”

See another recent study that proves the same point.

“There is controversy over dietary protein’s effects on cardiovascular disease risk factors in diabetic subjects. It is unclear whether observed effects are due to increased protein or reduced carbohydrate content of the consumed diets. The aim of this study was to compare the effects of two diets differing in protein to fat ratios on cardiovascular disease risk factors.”

What did their data show? Interestingly,…

“Both diets were equally effective in promoting weight loss and fat loss and in improving fasting glycemic control, total cholesterol and low-density lipoprotein (LDL) cholesterol, but the…HP–LF [high protein-low fat] diet improved significantly both systolic and diastolic blood pressure when compared with the LP–HF [low protein-high fat] diet. No differences were observed in postprandial glucose and insulin responses.”

The authors conclude:

“A protein to fat ratio of 1.5 in diets significantly improves blood pressure and TG [triglyceride] concentrations in obese individuals with DM2 [type 2 diabetes].”

“There is no evidence from randomized trials to support a strategy of lowering systolic blood pressure below 135 to 140 mm Hg in persons with type 2 diabetes mellitus. We investigated whether therapy targeting normal systolic pressure (i.e., <120 mm Hg) reduces major cardiovascular events in participants with type 2 diabetes at high risk for cardiovascular events.”

They constructed their study to discriminate outcomes between reducing blood pressure to less than 140 mm Hg and less than 120 mm Hg:

“A total of 4733 participants with type 2 diabetes were randomly assigned to intensive therapy, targeting a systolic pressure of less than 120 mm Hg, or standard therapy, targeting a systolic pressure of less than 140 mm Hg. The primary composite outcome was nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The mean follow-up was 4.7 years.”

I have told patients for years that it is not desirable to aggressively medicate blood pressure much below a systolic reading of 135-140 mm Hg because the increased pressure is a compensatory effort by the body to deliver oxygen to the tissues against increased resistance. There has to be a happy medium. What did the data from this investigation show?

“Serious adverse events attributed to antihypertensive treatment occurred in 77 of the 2362 participants in the intensive-therapy group (3.3%) and 30 of the 2371 participants in the standard-therapy group (1.3%).”

This compelled them to conclude that:

“In patients with type 2 diabetes at high risk for cardiovascular events, targeting a systolic blood pressure of less than 120 mm Hg, as compared with less than 140 mm Hg, did not reduce the rate of a composite outcome of fatal and nonfatal major cardiovascular events.