A session at the American College of Cardiology Annual Scientific Session titled “Hypertension: Risk Factors and Population Trends” provides further insights from the INVEST and LIFE studies, and reveals new information about the role of inflammation in hypertension.

Verapamil reduced stroke risk in INVEST
For the same level of blood pressure control in the INVEST trial, a nonsignificant trend towards a reduced risk of stroke with the verapamil-SR based treatment strategy, compared to the atenolol-based strategy, was found in a new analysis of the INVEST trial, reported by Dr. Carl Pepine, University of Florida, Gainesville. Strokes (fatal and nonfatal) occurred in 176 (1.6%) patients in the verapamil group and 201 (1.8%) patients in the atenolol group (hazard ratio 0.88, CI 0.72-1.08).

The study population was elderly, with a mean age of 66 years, about 50% female, and 50% Caucasian. Only 7% had a prior TIA or stroke. In the study, 70% of patients achieved a blood pressure level < 140/90 mm Hg.

Notably, patients who had a prior stroke had a significantly increased risk of stroke (fatal and nonfatal, adjusted hazard ratio 2.37), compared to patients who did not have a prior stroke.

The importance of blood pressure control to prevent stroke is reinforced by study results. Patients who had a stroke had worse systolic and diastolic blood pressure control (36.9% vs 60.4% of patients without a stroke (P<0.001). The mean treatment SBP was 142 mm Hg in those who had a stroke compared to 135 mmHg in those who did not (P<0.001).

Stroke risk increased with higher average systolic and diastolic blood pressures during the follow-up, regardless of the presence of the identified independent risk factors. Of the patients who had a stroke, only 46% had a blood pressure < 14/90 mm Hg. Frequencies of nonfatal stroke (20.3 vs 9.5%) and total stroke (5.0 vs 1.5%) were higher in patients with prior stroke than without stroke. In elderly patients, over 75 years of age, reducing their blood pressure to < 140/90 mm Hg, reduced their risk of stroke to the level of a person below 75 years of age.

New-onset diabetes was less with verapamil than atenolol. In total, there were 1200 new cases of diabetes.

Independent predictors for stroke were prior stroke/TIA, US residency, black race, increased age, diabetes, arrhythmia, revascularization, smoking, and prior MI as factors associated with increased stroke risk. Notably, baseline diastolic blood pressure was associated with increased risk for a second stroke, with each 5 mm Hg in diastolic blood pressure increasing risk by about 7%. There was no association between baseline systolic blood pressure and stroke risk.

Association between chronic kidney disease and CVD
The Kidney Early Evaluation Program (KEEP), a National Kidney Foundation sponsored screening program, reported that cardiovascular disease (CVD) was common among the 24,070 volunteers for the screening, who were at risk for chronic kidney disease (CKD. Further, estimated glomerular filtration rate (GFR), microalbuminuria, and anemia contribute to the reported CV risk in patients with CKD. Of the patients with known CVD in the screening, 71.2% had all three of these risk factors. Stage 3 CKD was associated with a 57.3% absolute prevalence of CVD, and stage 4-5 CKD a 71.2% absolute prevalence of CVD.

This epidemiologic study was designed to assess the risk of developing future CVD in persons with CKD. The study population had a mean age of 52 years and 70% was female, 47% hypertensive, 21% diabetic, 28% aged 31-45 years, 34% aged 40-60 years, and 22% aged 61-75 years.

“Based on these data and other reported data, CKD is an independent CV risk state,” stated Peter A. McCullough, William Beaumont Hospital, Royal Oak, MichiganFurther research by this group and others is working to elucidate which of these 3 factors (GFR, MA, anemia) is really operative. The National Institutes of Health is midway through a large-scale epidemiologic study called PRIC, which is trying to isolate the operative factors in CKD and the future development of de novo CVD.

LIFE: Risk prediction model compares to Framingham risk score
Dr. Sverre E. Kjeldsen, reported that the “LIFE risk prediction models” was constructed based on an analysis of the baseline characteristics in the LIFE study population, and that the utility of this model was compared to that of the Framingham risk score.

In the LIFE study, the mean age was 66 years, 54% were female, 13% had diabetes, and baseline blood pressure was 174//98 mm Hg. All patients had left ventricular hypertrophy (LVH). The primary endpoint was the composite of CV death, stroke, and MI, and its components. Losartan was more effective than atenolol in reducing the risk for the primary endpoint in the 9,193 patients followed for nearly 5 years.

Through a variety of statistical analyses, baseline variables were identified that affected the possibility of having a primary outcome, and a risk score was then developed for these variables. They were age per 10 years, male sex, current smoker, previous stroke/transient ischemic attack, atrial fibrillation, ischemic heart disease, total cholesterol,exercise >30 minutes twice per week, and LVH measured by Sokolow-Lyon and Cornell product.

The LIFE risk prediction model resulted in improved separation of the highest and lowest quartiles and deciles of risk than did the Framingham risk score. Further, the LIFE risk prediction model was equal to the Framingham risk score for MI, but was smoother than the Framingham score for predicting CV death, stroke, and the composite of these endpoints. The investigators state that the LIFE risk score may be useful for risk calculation, such as in guidelines and future clinical studies of patients with hypertension and LVH.

Minnesota Heart Survey: Blood pressure in normotensives slowly, but steadily, rising
The Minnesota Health Survey, conducted at 5-year intervals in the two largest cities in this state, showed that despite some improvements since 1980 in blood pressure detection, treatment, and control, there is a slow upward drift of 1-2 mm Hg in the blood pressure level in normotensives. The rising arterial blood pressure in normotensives may be related to the obesity epidemic and, from a public health perspective, signals concern about the potential increase in the hypertensive population, stated Dr. Russell Luepker, University of Minnesota.

This cross-sectional designed study randomly selected adults aged 25-64 years and collected standardized blood pressure measurements, medication inventories, and other health data. The average rate of participation was 65%, and in total, 10,207 men and 11,566 women were measured in five surveys.

Study findings show that about 12% of the general population is taking an antihypertensive agent, similar to the level in the 1980s, despite a dip in the 1990s. Notably, the use of lifestyle treatment for hypertension has decreased to about 40%%, after rising in use to about 60% in the 1990s.

For a blood pressure of 140/90 mmHg, treatment and control of hypertension was 20% in men and 27% in women in 1980-82, which decreased during the 1990s, but increased to 44% of men and 55% of women controlled for hypertension in 2000-02. Stage II hypertensives (160/95) were extraordinarily well detected and treated.

The interplay of inflammation and hypertension
An analysis of 601 participants in the Genetics of Coronary Artery Disease in Alaskan Natives (GOCADAN) study showed that inflammation, C-reactive protein, and homocysteine, play a role in hypertension. Whether or not these were causal in this study population is unclear, because of the very high prevalence of high seropositivity to CMV, HSV1, and H. pylori. Dr. Jianhui Zhu, Washington Medical Center, Washington, DC, reported the study.

The GOCADAN study comprises 1,214 Eskimos from about 40 families in Alaska. The mean age of the participants was 43 years; 45% were male, and 21% had hypertension, 3.4% diabetes, and 19% hypercholesterolemia.

The mean levels of CRP and homocysteine in the participants with and without hypertension were 3.6 vs. 2.7 mg/L (p=0.16) and 9.0 vs.7.1 micro mol/L (p<0.01), respectively. CRP and homocysteine above the 75th percentile were significantly associated with hypertension, even after adjusting for age, male sex, smoking, diabetes and hypercholesterolemia.

The adjusted odds ratio was 1.69 for high CRP, and 1.71 for high homocysteine levels.

Positive effects on vasculature with an ARB
The Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs Atenolol (SILVHIA) study reported by Dr. David Mörtsel, Karolinska, Stockholm, Sweden, showed that the angiotensin receptor blocker irbesartan reduced LV mass and favorably affected common carotid artery (CCA) intima-media thickness and area.

SILVHIA randomized 115 patients to irbesartan 150-300 mg or atenolol 50-100 mg, with hydrochlorothiazide or felodopine added as needed. Follow-up was 48 weeks. Although blood pressure was reduced similarly in the two groups,there was a greater reduction in LV mass in the irbesartan group (-28 g/m2 vs -14 g/m2 with atenolol).

A nonsignificant reduction with irbesartan in CCA intima-media thickness (from 0.92 mm, by -0.013 mm), but an increase with atenolol (from 0.94 mm, by +0.030 mm, p=0.003 between groups).

Atenolol reduced CCA lumen diameter more than irbesartan (from 6.2 mm, by -0.3 mm with atenolol; from 6.4 mm, by -0.2 mm with irbesartan; p=0.005 between groups).CCA intima-media area was reduced by irbesartan (from 21.3 mm2, by -0.90 mm2, p=0.034) but atenolol had no affect (from 21.3 mm, by -0.18 mm; p=0.041 between groups).

A relation between LV mass index and systolic blood pressure and CCA -media thickness and area was found.

Mörtsel stated that an ARB may reduce structural vascular changes beyond the effects of blood pressure reduction, and by mechanisms, at least in part, different from that observed in the heart. With similar reductions in blood pressure, irbesartan may improve cerebral blood flow compared to atenolol, which could help prevent cerebrovascular events.