Cardiovascular Mortality In Hypertensive Patients Research Articles

The relationship between mean corpuscular hemoglobin concentration and mortality in hypertensive individuals: A population-based cohort study.

Hematology is an essential field for investigating the prognostic outcomes of cardiovascular diseases (CVDs). Recent research has suggested that mean corpuscular hemoglobin concentration (MCHC) is associated with a poor prognosis in several CVDs. There is no evidence of a correlation between MCHC and hypertension. Therefore, our study aimed to analyze the association of MCHC with all-cause and cardiovascular mortality in hypertensive patients. We used cohort data from U.S. adults who participated in the National Health and Nutrition Examination Survey from 1999-2014. COX regression was applied to analyze the relationship between MCHC and all-cause and cardiovascular mortality. In addition, three models were adjusted to reduce confounding factors. We reanalyzed the data after propensity score matching (PSM) to inspect the stability of the results. Stratified analysis was additionally adopted to investigate the results of each subgroup. Our research included 15,154 individuals. During a mean follow-up period of 129 months, 30.6% of the hypertensive population succumbed to mortality. Based on previous studies, we categorized patients with MCHC ≤33mg/dl as the hypochromia group and those with >33mg/dl as the non-hypochromia group. After PSM, the hypochromia group had higher all-cause mortality (adjusted hazard ratio [HR]:1.26, 95% confidence interval [95%CI]:1.11-1.43) and cardiovascular mortality (adjusted HR:1.42, 95%CI:1.12-1.80) than the non-hypochromia group. The results of the COX regression remain stable after matching. Stratified analyses before PSM revealed an interaction of anemia in the relationship between MCHC and mortality, whereas there was no significant interaction after matching. In hypertensive individuals, low MCHC was correlated with a poor prognosis. Further studies on MCHC are necessary to analyze the potential mechanisms of its poor prognosis in hypertensive populations.

Renin-angiotensin system inhibitors reduce cardiovascular mortality in hypertensive patients with severe aortic stenosis undergoing transcatheter aortic valve implantation: insights from the EffecTAVI registry.

Arterial hypertension is associated with the triggering of the renin-angiotensin system, leading to left ventricle fibrosis and worse cardiovascular outcomes. In this study, patients with comorbid arterial hypertension and severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI) were selected from the EffecTAVI registry to evaluate the impact of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) on cardiovascular mortality. We enrolled 327 patients undergoing TAVI from the EffecTAVI registry. Using Kaplan-Meier event rates and study-stratified multivariable Cox proportional hazards regression models, we evaluated 2-year clinical outcomes according to the ACEI/ARB therapy status at enrollment. Among the included patients, 222 (67.9%) were on ACEIs/ARBs at baseline, whereas 105 (32.1%) were not. Treatment with ACEIs/ARBs was significantly associated with a 2-year decrease in the rate of cardiovascular mortality (HR = 0.44, 95% CI: 0.23-0.81, p = 0.009). This association remained stable after both multivariable adjustment and propensity score matching. In a cohort of hypertensive patients with severe AS who were selected from the EffecTAVI registry, ACEI/ARB treatment at baseline was found to be independently associated with a lower risk of 2-year cardiovascular mortality, suggesting a potential benefit of this treatment. More trials are needed to validate this finding and to understand the full benefit of this treatment.

Geriatric nutrition risk index in the prediction of all-cause and cardiovascular mortality in elderly hypertensive population: NHANES 1999-2016.

Hypertension is a major risk factor for the global burden of disease, and nutrition is associated with an increased risk of mortality from multiple diseases. Few studies have explored the association of nutritional risk with all-cause mortality and cardiovascular mortality in hypertension, and our study aims to fill this knowledge gap. We included data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2016 on a total of 10,037 elderly patients with hypertension. The nutritional status was evaluated using the Geriatric Nutrition Risk Index (GNRI). Kaplan-Meier survival analysis was performed to analyze the survival rates of different nutritional risk groups. COX proportional risk regression models were used to analyze the predictive effect of GNRI on all-cause mortality and cardiovascular mortality in hypertensive patients. Restricted cubic splines (RCS) were used to explore the nonlinear relationship between GNRI and mortality. The mean age of the hypertensive patients was 70.7 years. A total of 4255 (42.3%) all-cause mortality and 1207 (17.2%) cardiovascular mortality occurred during a median follow-up period of 106 months. Kaplan-Meier showed a more significant reduction in survival for the moderate to severe malnutrition risk of GNRI. The adjusted COX proportional hazards model showed that the hazard ratios for all-cause mortality and cardiovascular mortality in the moderate to severe malnutrition risk group for GNRI were 2.112 (95% CI, 1.377,3.240) and 2.604 (95% CI, 1.603,4.229), respectively. The RCS showed that increased GNRI was associated with a reduced risk of all-cause mortality and cardiovascular mortality risk reduction. Malnutrition exposure assessed by GNRI effectively predicts the risk of all-cause mortality and cardiovascular mortality in the elderly with hypertension.

The relationship between the pan-immune-inflammation value and long-term prognoses in patients with hypertension: National Health and Nutrition Examination Study, 1999-2018.

Direct antihypertensive therapy in hypertensive patients with a high CVD risk can reduce the incidence of cardiovascular death but increase adverse cardiovascular events, so additional ways to identify hypertensive patients at high risk may be needed. Studies have shown that immunity and inflammation affect the prognoses of patients with hypertension and that the pan-immune-inflammation value (PIV) is an index to assess immunity and inflammation, but few studies have applied the PIV index to patients with hypertension. To explore the relationship between the PIV and long-term all-cause and cardiovascular mortality in patients with hypertension. Data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 with a mortality follow-up through December 31, 2019, were analyzed. A total of 26,781 participants were evaluated. The patients were grouped based on PIV levels as follows: T1 group (n = 8,938), T2 group (n = 8,893), and T3 group (n = 8,950). The relationship between the PIV and long-term all-cause and cardiovascular death was assessed by survival curves and Cox regression analysis based on the NHANES recommended weights. The PIV was significantly associated with long-term all-cause and cardiovascular mortality in patients with hypertension. After full adjustment, patients with higher PIV have a higher risk of all-cause [Group 3: HR: 1.37, 95% CI: 1.20-1.55, p < 0.001] and cardiovascular [Group 3: HR: 1.62, 95% CI: 1.22-2.15, p < 0.001] mortality. Elevated PIV was associated with increased all-cause mortality and cardiovascular mortality in hypertensive patients.

Empagliflozin Downregulates Renal NHE3 Activity and NaPi‐2 Expression and Reduces Blood Pressure in Hypertensive Rats

Sodium-glucose cotransporter 2 (SGLT2) inhibitors, also known as gliflozins, can lower blood pressure (BP) and reduce cardiovascular mortality in hypertensive patients with type 2 diabetes. However, the molecular mechanisms underlying the antihypertensive effects of the SGLT2 inhibitors have not been elucidated. This study tested the hypothesis that empagliflozin, an SGLT2 inhibitor, reduces BP of nondiabetic hypertensive rats and that this effect may be associated with altered expression and/or covalent modification of apical sodium transporters in the renal proximal tubule. To this end, spontaneously hypertensive rats (SHR) and normotensive Wistar rats (12-14 weeks of age) were treated for 2 weeks with empagliflozin 10 mg/kg/day or vehicle (water) orally. BP was measured non-invasively (tail-cuff plethysmography) and invasively (arterial catheterization). Proximal tubule Na+/H+ exchanger isoform 3 (NHE3) activity was assessed by in vivo stationary microperfusion. NHE3 phosphorylated at serine 552 (pNHE3-552), total NHE3 and Na+-dependent phosphate cotransporter type II (NaPi-2) expression in the renal cortex were evaluated by immunoblotting. We found that vehicle-treated SHR exhibited a small increase in BP (9±2 mmHg), whereas empagliflozin reduced BP of hypertensive rats (-10±2 mmHg). No changes in BP were observed in Wistar rats. The in vivo stationary microperfusion analyses showed that empagliflozin inhibited the activity of NHE3 in both hypertensive and normotensive rats. Inhibition of NHE3 activity by empagliflozin was not accompanied by differences in the levels of pNHE3-552 or total NHE3 expression in the renal cortex. On the other hand, NaPi-2 expression was upregulated in the renal cortex of vehicle-treated SHR (226±18 vs. 100±5% in vehicle-treated Wistar rats, p< 0.0001), and treatment with empagliflozin significantly reduced it (163±11 vs. 226±18%, p< 0.01). Renal cortical NaPi-2 abundance was not affected by empagliflozin in normotensive rats. These findings demonstrate empagliflozin lowers blood pressure in nondiabetic hypertensive rats. Moreover, it shows that SGLT2 inhibition may reduce proximal tubule sodium reabsorption via inhibition of NHE3 and downregulation of NaPi-2. Future studies are necessary to evaluate the impact of SGLT2 inhibitors in the distal nephron and its association with the antihypertensive effects of the gliflozins.

SCORE underestimates cardiovascular mortality in hypertension: insight from the OLD-HTA and NEW-HTA Lyon cohorts.

Current European guidelines recommend the SCORE to estimate 10-year cardiovascular mortality in patients with moderate/low cardiovascular risk. SCORE was derived from the general population. The objective of this study was to investigate the estimated 10-year cardiovascular mortality according to the SCORE in a historic and a contemporary cohort of hypertensive patients. After exclusion of secondary prevention and diabetes, 3086 patients were analysed in the OLD-HTA (1969-90) and 1081 in the NEW-HTA (1997-2014) Lyon cohorts. SCORE was calculated using the low and high cardiovascular risk equations and charts, and patients classified as being at low (0%), moderate (1-4%), high (5-9%), and very high (≥10%) risk. In the OLD-HTA cohort, 10-year cardiovascular mortality was higher (1.2%, 5.5%, 17.7%, and 27.0%) than that predicted by the low-risk equation (0%, 1.7%, 6.4%, and 14.8%). In the NEW-HTA cohort, similar results were observed (1.1%, 4.7%, 15.1%, and 15.2% vs. 0%, 1.9%, 6.2%, and 11.7%, respectively). Using the high-risk equation, mortality was underestimated in both cohorts, but the difference was smaller. The diagnostic performance of the high-risk equation was lower than the low-risk equation in both cohorts, considering the SCORE as a continuous or a categorical variable (Likelihood ratio test P < 0.05 for all comparisons in OLD-HTA). Similar results were obtained using SCORE charts. SCORE underestimates the 10-year cardiovascular mortality risk in hypertensive patients in a historic cohort and in a contemporary one. The algorithm to predict cardiovascular mortality in hypertensive patients needs an update given new information since its creation.

Comparison of Nebivolol and Bisoprolol for Cardiovascular Mortality in Hypertensive Patients.

IntroductionBeta-blockers again are now considered as first-line therapy for various cardiovascular diseases. In this study, we compare the cardiovascular event between two beta-blocker, i.e. Nebivolol and Bisoprolol.Materials and MethodsIt is a two-arm open-label randomized prospective study that was conducted from 1st Jan 2016 to 30th July 2019 in tertiary care hospital, Nawabshah. One thousand and fifty-six (n=1056) hypertensive patients were enrolled after informed consent, which were randomized into two equal groups. Patients were followed up for one year.ResultsComparison between Nebivolol and Bisoprolol showed that all-cause mortality (9.8% vs 11.48%), cardiovascular mortality (5.4% vs 7.0%), all-cause hospitalization (14.4% vs 16.3%), and cardiovascular hospitalization (9.8% vs 12.09%) was numerically lower in nebivolol but the difference was not statistically significant.ConclusionFurther large scale multicentric trials with a longer follow up period are needed to compare various beta-blockers for cardiovascular event.

Dietary nitrate load lowers blood pressure and renal resistive index in patients with chronic kidney disease: A pilot study

Beetroot has a high concentration of inorganic nitrate, which can serially reduced to form nitrite and nitric oxide (NO) after oral ingestion. Increased renal resistive index (RRI) measured by Doppler ultrasonography is associated with higher cardiovascular mortality in hypertensive patients with reduced renal function over time defined as chronic kidney disease (CKD). Our aim was to investigate whether the supplementation of dietary nitrate by administration of beetroot juice is able to reduce blood pressure and renal resistive index (RRI) as prognostic markers for cardiovascular mortality in CKD patients.In a cross-over study design, 17 CKD patients were randomized to either a dietary nitrate load (300 mg) by highly concentrated beetroot juice (BJ) or placebo (water). Hemodynamic parameters as well as plasma nitrate concentration and RRI were measured before and 4 h after treatment.In this cohort, CKD was mainly caused by hypertensive or diabetic nephropathy. The mean eGFR was 41.6 ± 12.0 ml/min/m2. Plasma nitrate concentrations were significantly increased after ingestion of BJ compared to control. Peripheral systolic and diastolic blood pressure as well as mean arterial pressure (MAP) were significantly reduced secondary to the dietary nitrate load compared to control (e.g. ΔMAPBJ = −8.2 ± 7.6 mmHg vs. ΔMAPcontrol = −2.2 ± 6.0 mmHg, p = 0.012). BJ also led to significantly reduced RRI values (ΔRRIBJ = −0.03 ± 0.04 versus ΔRRIcontrol = 0.01 ± 0.04; p = 0.017). Serum potassium levels were not altered secondary to the treatment.In this study, administration of the nitrate donor BJ led to significantly reduced RRI values and peripheral blood pressure which might be explained by release of the vasodilatator NO after oral intake. Whether supplementation of dietary nitrate in addition to routine pharmacologic therapy is able to decelerate progression of cardiovascular and renal disease in CKD, remains to be investigated.

Potential beneficial impact of angiotensin receptor blockers on arterial stiffness in hypertension

Hypertension is highly prevalent worldwide and is one of the major risk factors for cardiovascular and renal diseases. Accumulated results of clinical trials showed that strict control of blood pressure (BP) is essential to prevent target organ damage and to reduce cardiovascular mortality in hypertensive patients. In many countries, major antihypertensive drugs are calcium channel blockers (CCBs), angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors, diuretics, and beta-blockers (including alpha/beta-blockers), according to the international hypertension guidelines (1-5).

Cardiovascular mortality in hypertensive patients newly prescribed perindopril vs. lisinopril: A 5-year cohort study of 15,622 Chinese subjects

BackgroundPerindopril and lisinopril are two common ACE inhibitors prescribed for management of hypertension. Few studies have evaluated their comparative effectiveness to reduce mortality. This study compared the all-cause and cardiovascular related mortality among patients newly prescribed ACE inhibitors. MethodsAll adult patients newly prescribed perindopril or lisinopril from 2001 to 2005 in all public clinics or hospitals in Hong Kong were retrospectively evaluated, and followed up until 2010. Patients prescribed the ACE inhibitors for less than a month were excluded. The all-cause mortality and cardiovascular-specific (i.e. coronary heart disease, heart failure and stroke) mortality were compared. Cox proportional hazard regression model was used to assess the mortality, controlling for age, sex, socioeconomic status, patient types, the presence of comorbidities, and medication adherence as measured by the proportion of days covered. An additional model using propensity scores was performed to minimize indication bias. ResultsA total of 15,622 patients were included in this study, in which 6910 were perindopril users and 8712 lisinopril users. The all-cause mortality (22.2% vs. 20.0%, p<0.005) and cardiovascular mortality (6.5% vs. 5.6%, p<0.005) were higher among lisinopril users than perindopril users. From regression analyses, lisinopril users were 1.09-fold (95% C.I. 1.01–1.16) and 1.18-fold (95% C.I. 1.02–1.35) more likely to die from any-cause and cardiovascular diseases, respectively. Age-stratified analysis showed that this significant difference was observed only among patients aged >70years. The additional models controlled for propensity scores yielded comparable results. ConclusionsThe long-term all-cause and cardiovascular related mortality rates of lisinopril users was significantly different from those of perindopril users. These findings showed that intra-class variation on mortality exists among ACE inhibitors among those aged 70years or older. Future studies should consider a longer, large-scale randomized controlled trial to compare the effectiveness between different medications in the ACEI class, especially among the elderly.

Questionable link between normo- to microalbuminuria and home-measured blood pressure variability in hypertension

The accumulated results of clinical trials have shown that the strict control of blood pressure (BP) is essential for preventing target organ damage and reducing cardiovascular mortality in hypertensive patients (Figure 1). Although hypertension is usually diagnosed based on measurements of BP recorded during a visit to a physician (that is, office BP), several studies have shown that target organ damage and prognosis are more closely associated with ambulatory BP or home BP than with office BP. At present, hypertensive patients with albuminuria are increasing in number and cardiovascular complications are the most common cause of death in these hypertensive patients with albuminuria. Thus, it would be of considerable value to identify the mechanisms involved in the cardiovascular events associated with hypertension complicated with albuminuria.

Enduring Direct Association of Baseline Plasma Renin Activity With All-Cause and Cardiovascular Mortality in Hypertensive Patients

Plasma renin activity (PRA) has been associated with cardiovascular disease mortality (CVD) events among hypertensive patients. We now report a long-term follow-up to assess the enduring association of PRA to CVD and all-cause mortality. Participants (3,791) in a systematic hypertension treatment study had entry systolic blood pressure (BP) ≥140 mm Hg and mean age 52. CVD and all-cause mortality was ascertained for mean of 16 years. Pretreatment PRA was analyzed as a continuous variable, and by tertiles. The 10-year Framingham score was similarly examined. Hazard ratios (HRs) were estimated from multivariate Cox proportional hazard models. There were 804 deaths, and 360 (45%) were CVD. PRA was associated with all-cause mortality and CVD, but not cancer or non-CVD. Although T3 had lower mean baseline and follow-up systolic BP than T1, (146 vs. 152 mm Hg (P < 0.001) and 135 vs. 139 mm Hg (P < 0.001), respectively), T3 had 37% higher all-cause mortality (HR: 1.37, 95% confidence interval (CI): 1.15-1.63, P < 0.001) and 70% higher CVD mortality (HR: 1.70, 95% CI: 1.29-2.23, P < 0.001) after adjustment. The difference between T3 and T1 in mortality from coronary artery disease and myocardial infarction was more pronounced than for all CVD. PRA also significantly improved CVD risk estimation provided by Framingham. These findings extend and reinforce previous evidence that pretreatment PRA has a significant, independent, specific, and direct long-term association with CVD mortality. Moreover, PRA adds significantly to risk identified by the Framingham score.

The Relationship Between Ambulatory Arterial Stiffness Index and Blood Pressure Variability in Hypertensive Patients

Background and ObjectivesAmbulatory arterial stiffness index (AASI) is well known as a predictor of cardiovascular mortality in hypertensive patients. Mathematically, AASI reflect the standard deviation (SD) of blood pressure (BP) variation. AASI is measured higher levels in non-dipper than dipper. Thus, AASI has a possibility of not only reflecting arterial stiffness but also BP variability and/or autonomic nervous dysfunction.Subjects and MethodsConsecutive data from 418 untreated hypertensive patients were analyzed retrospectively. We examined the association between the 24-hour ambulatory BP monitoring (ABPM) parameters and AASI.ResultsAASI had a simple correlation with age (R=0.189, p<0.001), relative wall thickness (RWT) (R=0.115, p=0.019), left ventricular mass index (LVMI) (R=0.192, p<0.001), average systolic BP (SBP) (R=0.232, p<0.001), average pulse pressure (PP) (R=0.363, p<0.001), SD of diastolic BP (DBP) (R=-0.352, p<0.001), SD of PP (R=0.330, p<0.001), SD of heart rate (HR) (R=-0.268, p<0.001), and nocturnal dipping (R=-0.137, p=0.005). In multiple linear regression analysis model including clinical parameters and 24 hour-ABPM parameters, independent predictors of AASI were SD of PP (β=1.246, p<0.001), SD of DBP (β=-1.067, p<0.001), SD of SBP (β=-0.197, p<0.001), and non-dipper (β=0.054, p=0.033).ConclusionAASI is closely correlated with BP variability. The result of this study shows that AASI is not only a parameter for arterial stiffness, but also a parameter for BP variability.

A comparison of the effects of ramipril and losartan on blood pressure control and left ventricle hypertrophy in patients with autosomal dominant polycystic kidney disease

Background: Hypertension is frequently seen in autosomal dominant polycystic kidney disease (ADPKD), and it has a negative effect on renal progression. Hypertension and left ventricle hypertrophy (LVH) are related in terms of pathogenesis and their effects on renal progression. In this study, we aimed to compare the effects of losartan and ramipril on blood pressure (BP) control, LVH, and renal progression in patients with hypertensive ADPKD. Methods: Thirty-two ADPKD patients with ages ranging between 18 and 70 years who were stage 1–2 hypertensive were included in this study. Routine biochemical tests and echocardiography were obtained at first examination of the patients. Following these, the patients were randomized. One group was given losartan and the other ramipril. They were followed up for 1 year, and their echocardiographies and routine biochemical tests were repeated at the end of the year. Results: BP values decreased in both the groups at the end of the first year (p < 0.001). There was a statistically significant difference in LVH in both the groups at the end of the first year than at the beginning (losartan, p = 0.007; ramipril, p < 0.001). Conclusions: In this study, effective BP control was obtained with losartan and ramipril and LVH was found to be regressed significantly in the hypertensive patients with ADPKD. These two groups of antihypertensive drugs may also have beneficial effects on the retardation of renal progression and in reducing cardiovascular mortality in hypertensive patients with ADPKD.

Surrogate Measures of Arterial Stiffness

Recent epidemiological studies have shown that arterial stiffness, measured through carotid-femoral pulse wave velocity (PWV), has an independent predictive value for cardiovascular (CV) events in several populations, including patients with uncomplicated essential hypertension1,2 and type 2 diabetes.3 Arterial stiffness is thus an intermediate end point for CV events, predicting CV events independently of and beyond peripheral pulse pressure (PP). Peripheral PP, central PP, and augmentation index, which provide additional information on wave reflection, are considered “surrogates” of arterial stiffness, because their pathophysiological meaning is clearly different.4–6 Central PP and augmentation index are dependent on the speed of wave travel, the amplitude of reflected wave, the reflectance point, and the duration and pattern of ventricular ejection, especially with respect to change in heart rate and ventricular contractility. Aortic PWV, which is the speed of wave travel, represents intrinsically arterial stiffness, according to the Bramwell-Hill formula.4–6 Two articles7,8 in the present issue of Hypertension raise the issue of the predictive value of “surrogates of arterial stiffness” for CV events. Li et al7 studied the dynamic relationship between diastolic blood pressure (DBP0 and systolic blood pressure (SBP) in ambulatory blood pressure monitoring (ABPM) data throughout the day and calculated a novel index as 1− the regression slope of DBP on SBP. This index was named ambulatory arterial stiffness index (AASI) on the basis that “average distending BP …

Making Up and Breaking Up

The concept that blood pressure influences vessel wall composition and structure is well established. Any alterations in stretch (caused by changes in blood pressure) solicit counteracting radial and tangential forces, driving transformations in the vessel wall that aim to accommodate the new conditions and to ultimately restore basal levels of tensile stress.1–3 Thus, when tensile stress increases because of a rise in arterial pressure, smooth muscle cell hypertrophy and collagen and elastin contents augment. Inversely, when the circumferential stress falls, the wall undergoes atrophy.4,5 See page 957 Understanding how vessel wall remodeling occurs is valuable because it relies on the delicate balance between restructuralization and overcompensation. For instance, vascular accumulation of type I, III, and IV collagen in hypertensive patients6 and in animal models of hypertension7,8 effectively counteracts the distending force of blood pressure, but at length it also results in increased vascular stiffness. Clinically, vascular stiffness translates to greater pulse wave velocity, which is an independent predictor of mortality in patients with end-stage renal failure, hypertension, and diabetes, as well as in older individuals.9 In this issue of Atherosclerosis, Thrombosis and Vascular Biology , Jackson et al10 show that the opposite holds true for vessels in which axial tension is off-loaded. In rabbit carotid arteries elongated by interposition of the contralateral carotid artery, the authors found that tortuosity caused by loss of axial strain was not rectified in the months that followed the intervention. Smooth muscle cell proliferation was observed, but this was offset by equivalent cell apoptosis. Likewise, elastin and collagen accumulation was countered by matrix metalloproteinase (MMP) upregulation and activation. But on close observation of the extracellular matrix (ECM), it became apparent that the fenestrae of the internal elastic laminae were greatly enlarged, and indeed the authors found that …

Retrospective longitudinal cohort study comparing the effects of angiotensin-converting enzyme inhibitors and long-acting calcium channel blockers on total and cardiovascular mortality in patients with hypertension

Background: There is controversy regarding the impact that different antihypertensive regimens, including modern combination therapy, have on the incidence of myocardial infarction, other cardiovascular events, and mortality.Objective: The objective of this study was to determine and compare the effects of treatment strategies based on angiotensin-converting enzyme (ACE) inhibitors and long-acting calcium channel blockers (CCBs) on total and cardiovascular mortality in hypertensive patients in a usual-care setting.Methods: This retrospective, longitudinal cohort study used integrated medical and pharmacy claims data from a geographically diverse administrative database of >8 million persons in the United States. Patients aged ≥18 years with hypertension were eligible if they had filled a prescription for either an ACE inhibitor or a long-acting CCB between January 1, 1995, and June 30, 1999 (the index prescription). Patients who had a prescription for any antihypertensive agents before the index prescription were excluded, as were eligible ACE inhibitor-treated patients who used CCBs or CCB-treated patients who used ACE inhibitors during the follow-up period. Use of all other antihypertensive medications was permitted. Patients were matched using a propensity score generated from a logistic regression model. A survival-analysis approach was used to compare mortality between groups. The final cohorts were assessed through June 30, 2002.Results: A total of 18,199 patients met the study inclusion criteria; 12,608 (69.3%) used an ACE inhibitor and 5591 (30.7%) used a CCB. The mean follow-up was ∼4.4 years. After cohort matching using the propensity score, the study population consisted of 10,926 patients, 5463 matched patients in each group. The adjusted hazard ratios (95% CIs) for all-cause, cardiovascular, congestive heart disease, and congestive heart failure mortality in the ACE-inhibitor group compared with the CCB group for the entire follow-up period were 0.70 (0.63–0.79), 0.65 (0.53–0.80), 0.47 (0.32–0.70), and 0.74 (0.49–1.12), respectively.Conclusion: Analysis of a large medical and pharmacy database suggests that an ACE inhibitor-based treatment strategy is associated with reduced mortality compared with a CCB-based strategy in patients with hypertension in a managed care setting.

Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients.

Although various studies reported that pulse pressure, an indirect index of arterial stiffening, was an independent risk factor for mortality, a direct relationship between arterial stiffness and all-cause and cardiovascular mortality remained to be established in patients with essential hypertension. A cohort of 1980 essential hypertensive patients who attended the outpatient hypertension clinic of Broussais Hospital between 1980 and 1996 and who had a measurement of arterial stiffness was studied. At entry, aortic stiffness was assessed from the measurement of carotid-femoral pulse-wave velocity (PWV). A logistic regression model was used to estimate the relative risk of all-cause and cardiovascular deaths. Selection of classic risk factors for adjustment of PWV was based on their influence on mortality in this cohort in univariate analysis. Mean age at entry was 50+/-13 years (mean+/-SD). During an average follow-up of 112+/-53 months, 107 fatal events occurred. Among them, 46 were of cardiovascular origin. PWV was significantly associated with all-cause and cardiovascular mortality in a univariate model of logistic regression analysis (odds ratio for 5 m/s PWV was 2.14 [95% confidence interval, 1.71 to 2.67, P<0.0001] and 2.35 [95% confidence interval, 1.76 to 3.14, P<0.0001], respectively). In multivariate models of logistic regression analysis, PWV was significantly associated with all-cause and cardiovascular mortality, independent of previous cardiovascular diseases, age, and diabetes. By contrast, pulse pressure was not significantly and independently associated to mortality. This study provides the first direct evidence that aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in patients with essential hypertension.

Alcohol Consumption And Cardiovascular Mortality In Hypertensive Patients

P83 Background: Alcohol drinking is associated with a dose-dependent increase in blood pressure, and JNC VI advises limiting alcohol consumption in patients with hypertension. Data are sparse on relationship between alcohol consumption and mortality in hypertensive patients. We therefore assessed whether alcohol consumption is associated with decrease in total, and cardiovascular mortality among subjects with hypertension. Methods: From the enrollment cohort of 89,251 men from the Physicians’ Health Study who provided self-reported information on alcohol intake and were free of myocardial infarction, stroke, cancer or liver disease at baseline, we identified a group of 14,125 persons with a history of current or past treatment for hypertension. Results: During 75,710 person-years of follow up, there were 1,018 deaths including 579 from cardiovascular disease and 224 from cancer. In multivariate analyses that controlled for several potential confounders, moderate alcohol intake was associated with significant decrease in cardiovascular mortality (P&lt;0.001 for linear trend). Compared with non-drinking men, those who drank 1 to 3 drinks per month had a RR for cardiovascular mortality of 0.86 (CI 0.63-1.18, P=0.35); for 1 to 6 drinks per week, the RR was 0.64 (CI 0.51-0.81, P&lt;0.001); for &gt;= 1 drink per day the RR was 0.57 (CI 0.44-0.72, P&lt;0.001). RR values for all-cause mortality in the same groups were respectively 0.89 (CI 0.70-1.15, P=0.38); 0.73 (CI 0.60-0.88, P=0.001); and 0.73 (CI 0.61-0.89, P=0.0014)(P=0.0025 for linear trend). On the other hand, we found no significant association between moderate alcohol consumption and cancer mortality (P=0.68 for linear trend). Conclusion: These results suggest that light to moderate alcohol consumption is associated with a significant reduction in cardiovascular and all-cause mortality in patients with hypertension.

Increased cardiovascular mortality in hypertensive patients with renal artery stenosis. Relation to sympathetic activation, renal function and treatment regimens.

Previous studies in hypertensive patients with renovascular disease have shown both elevated sympathetic nerve activity and increased cardiovascular mortality. The aim of the present study was to assess long-term survival in hypertensive patients with renal artery stenosis in relation to sympathetic activation, renal function and treatment regimens. A total of 169 consecutive patients aged 54 +/- 1 years with hypertension underwent a clinical investigation for renovascular hypertension including renal angiography and measurement of bilateral renal renin secretion. In 107 of these patients, arterial plasma concentrations of noradrenaline were measured. The mean follow-up time was 7.1 +/- 0.3 years and survival data were available in all patients up to May 1997. For comparison, healthy age-matched normotensive controls were examined. Arterial noradrenaline concentrations were threefold elevated in hypertensive patients with renal artery stenosis compared to healthy controls (P < 0.01). During the follow-up time, 44 patients died. Cardiovascular mortality accounted for 75% of all deaths. The risk ratio for overall mortality in hypertensive patients with renal artery stenosis compared to the normal population of Sweden, matched for age, was 3.3 (2.4-4.4), whereas the risk ratio for cardiovascular mortality was 5.7 (3.9-8.0). The arterial plasma concentration of noradrenaline was 3.11 +/- 0.30 pmol/ml in patients who died compared to 3.84 +/- 0.26 pmol/ml in survivors. Reduced renal function and age were independent predictors of death. Survival did not differ between patients undergoing intervention with either renal angioplasty or surgical reconstruction for renal artery stenosis and patients not undergoing intervention. Although sympathetic nerve activity is elevated in hypertensive patients with renal artery stenosis, our results do not suggest that this adrenergic over-activity is directly linked to the observed high cardiovascular mortality. Mortality in hypertensive patients with renovascular disease remains high whether an interventional treatment is performed or not, possibly due to the concomitant coronary disease.