The cardiovascular disease continuum is a sequence of events, which begins with a host of risk factors consisting of diabetes mellitus, dyslipidemia, hypertension, smoking and visceral obesity. If left untreated, it will inexorably progress to atherosclerosis, CAD, myocardial infarction, left ventricular remodeling, LVH, left ventricular enlargement, and eventually end-stage heart failure and death. Treatment intervention at any stage of its course will prevent or delay its further progression. However, the best results are expected to be achieved when treatment is initiated at the beginning, or at an early stage of its course. A Pub-Med/MEDLINE search was conducted for relevant English language, randomized clinical trials and epidemiologic studies for the years 1995-2009 using the terms, cardiovascular continuum, obesity, hyperlipidemia, diabetes mellitus, hypertension, metabolic syndrome, renal disease, stroke, and blockers of the renin angiotensin system (RAS). A total of 34 pertinent studies were selected for review. This concise review will focus on prevention and the aggressive treatment of the existing cardiovascular risk factors with emphasis on the blockers of RAS, and demonstrate that RAS blockers are the best drugs for its treatment.

The antihypertensive and metabolic effects of amlodipine, a new calcium-channel blocker, in combination with hydrochlorothiazide (HCTZ) were compared with those of HCTZ in combination with placebo. After four weeks open treatment with HCTZ 50 mg/d, 20 patients were blindly allocated to receive placebo and 20 to receive amlodipine, if their diastolic arterial pressure supine and upright was 95 to 115 mm Hg. The patients were seen in the clinic every two weeks for 12 more weeks, where their arterial pressure (AP) and heart rate (HR) were measured supine and upright. Hydrochlorothiazide was kept at 50 mg/d, but amlodipine was increased from 2.5 to 5.0 to 10.0 mg/d as needed. At end of weeks 4 and 16 the AP and HR were measured hourly for 12 hours and 24 hours later. Serial clinical and laboratory evaluations including lipid profiles were done on all patients. Amlodipine treated patients had lower arterial pressures in both the supine and upright positions (P less than .001), higher HDL levels (P less than .05) and lower CHOL:HDL and LDL:HDL ratios (P less than .01), than placebo-treated patients. Also, amlodipine-treated patients had lower SGOT and SGPT levels (P less than .01) than placebo-treated patients. No changes in HR or weight were noted between the two groups of patients. Clinical side effects were few and mild and not different between the two groups. We conclude: (1) the addition of amlodipine to HCTZ enhanced its antihypertensive action; (2) amlodipine was safe and well tolerated; and (3) amlodipine, perhaps, has a favorable effect on lipids.

The hemodynamic and metabolic effects of dietary induced hypomagnesemia were studied in two groups of 2-month-old male spontaneously hypertensive rats (SHR). All rats were given distilled water to drink ad libitum and were followed for 2 months. However, control rats (n = 12) were given a regular rat diet to eat, whereas the experimental (hypomagnesemic; HM) rats (n = 12) were given a magnesium-free diet. Metabolic and hemodynamic studies were done at the end of the 2-month observation period in the awake state. HM rats had higher mean arterial pressure, total peripheral resistance, renal vascular resistance, heart rate, U_NaV, U_kV and serum Na, and lower hematocrit, renal blood flow, serum K and serum Mg than the controls. No differences were observed among the two groups of rats with respect to weight, fluid intake, urine volume, serum calcium, blood urea nitrogen, cardiac index and glomerular filtration rate. In addition, HM rats had widespread myocardial and renal tissue calcification in contrast to controls, which did not show any tissue calcification. We conclude: (1) dietary-induced hypomagnesemia aggravated the hypertension of SHR; (2) it caused widespread tissue calcification; (3) the adverse effects of hypomagnesemia on arterial pressure were possibly produced through calcium-mediated systemic vasoconstriction and increase in peripheral vascular resistance.

The open, long-term antihypertensive, hemodynamic and metabolic effects of betaxolol in combination with furosemide and minoxidil were investigated on 30 male patients with moderate to severe essential hypertension. Twenty-three patients were observed for 104 weeks, and 7 patients for 128 weeks. The patients were seen in the clinic every 4 weeks. Blood chemistries, electrocardiograms, chest x-rays and echocardiograms were done at set intervals during the study. This drug combination caused a significant and sustained decrease in arterial pressure and heart rate (p < 0.001), a significant increase in the cardiothoracic ratio (p < 0.05), left and right ventricular diameter in end diastole and in left ventricular mass (p < 0.001), and had no effect on left ventricular wall thickness, interventricular septal thickness, left ventricular ejection fraction, myocardial fiber shortening or metabolic functions. Clinical side effects included hypertrichosis, weight gain and edema. We conclude: (1) Single daily administration of betaxolol, furosemide and minoxidil produced a significant and sustained antihypertensive effect. (2) It caused cardiac enlargement and increased left ventricular mass without deterioration of myocardial function. (3) The clinical significance of the latter findings is not known at present time.

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