Hypertension and the High Risk Diabetic Patient

 By Owen Yen, M.D.

(presented at the CAMS 2005 Annual Scientific Meeting)

 Hypertension is one of the major public health issues in this country.  With recent clinical trials, it has become very clear that even minor BP elevation has strong implications for future cardiovascular events. JNC-7 added the new category of “prehypertension” when a person’s blood pressure is over 120/80 mmHg. In rapidly developing country such as China, adaptation to modern lifestyles and eating habits has created significant problems with weight and hypertension.  Diabetes is on the rise in most countries because of the trend of eating "fast foods" and reduced physical activities.  Unfortunately, the combination of hypertension and diabetes and the metabolic syndrome synergistically increases the person's risk for cardiovascular event.

Death from ischemic heart disease increases linearly from BP >115/75 mmHg. For every 20 mmHg systolic or 10 mmHg diastolic increase in BP, there is a doubling in ischemic heart or stroke risk.

The goal is to achieve BP of  <140/90 mmHg with the goal at 130/80 mmHg in patients with diabetes or renal disease. Lifestyle modifications with weight reduction, diet, and exercise should be recommended to all patients. Thiazide diuretics alone or in combination are recommended by JNC-7 as initial therapy. Other classes are angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), Beta-blockers (BBs), and calcium channel blockers (CCBs). In major clinical trials, majority of patients needs two or more agents to achieve their BP goals.

 The worldwide incidence of type II diabetes is on the rise. Unfortunately, diabetics with no prior myocardial infarction (MI) has the same risk for a cardiovascular event as a non-diabetic who already had a MI. This is because insulin resistance has already been doing their “dirty work” for 10-12 years prior to the clinical diagnosis of diabetes. The controversial diagnosis of Metabolic Syndrome essentially identifies those at high risk for cardiovascular events because of increased insulin resistance and vascular inflammation.  One of the characteristics of the Metabolic Syndrome is increased waist circumference (men >40 inch & women >35 inch). This correlates with increased visceral fat desity. Visceral fat is metabolically very active. Visceral fat secretes free fatty acids, TNF-alpha, adiponectin, IL-6, PAI-1, leptin, and angiotensinogen – to name a few.

 One of the major regulator of blood pressure in mammals is the rennin-angiotensin  system.  Because of the crosstalk between the different hormonal system, the use of ACE inhibitors and hypertension will reduced the onset of diabetes as proven in the HOPE trial.  Recent trials using angiotensin receptor blockers suggest that they are a good substitute for the ACE inhibitors especially in those who cannot tolerate ACE inhibitors.  For patients who are hypertensive, pronteinuria of more than one gram per day is prognostic for progressive renal failure.  Calcium channel blockers has proven effective in hypertensive patients who do not have diabetes or renal failure.  Their efficacy in diabetic or in heart disease population is open to question.  Because the BP goal in diabetic population is < 130/80 mmHg, majority of patient will need at least three separate antihypertensive agents.  There has been controversy in the use of beta-blocker in diabetics.  However, recent studies suggest that diabetic patients have increased sympathetic system activities and increases myocardial utilization of free fatty acids.  This results in increased myocardial oxygen demand.  Both angiotensin blockade and beta-blockade have demonstrated that they can reverse cardiac remodeling and reduces myocardial wall stress.  In a meta-analysis of 18 hypertension trials, beta blockade reduces stroke risk by 29%, myocardial infarction by 7%, and heart failure by 42%. In UKPDS, aggregate clinical end points favors beta-blocker over ACE inhibitors. The choice of beta-blockers in patients with left ventricular dysfunction may be important based on large scale heart failure trials which showed all beta-blockers are not the same.

Lastly, work in genetics have shown us that multiple variants in gene phenotypes affect our blood pressure and the “inherited” tendency of hypertension is probably mpre complicated than we thought. Gene therapy will unlikely be available in the foreseeable future.

 Dr. Yen is Clinical Assistant Professor of Medicine, SUNY at Stony Brook School of Medicine.