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Despite all available therapies, the rates of hospitalization and death from heart failure (HF) remain unacceptably high. The most common reasons for hospital admission are symptoms related to congestion. During hospitalization, most patients respond well to standard therapy and are discharged with significantly improved symptoms. Post-discharge, many patients receive diligent and frequent follow-up. However, rehospitalization rates remain high. One potential explanation is a persistent failure by clinicians to adequately manage congestion in the outpatient setting. The failure to successfully manage these patients post-discharge may represent an unmet need to improve the way congestion is both recognized and treated. A primary aim of future HF management may be to improve clinical surveillance to prevent and manage chronic fluid overload while simultaneously maximizing the use of evidence-based therapies with proven long-term benefit. Improvement in cardiac function is the ultimate goal and maintenance of a “dry” clinical profile is important to prevent hospital admission and improve prognosis. This paper focuses on methods for monitoring congestion, and strategies for water and sodium management in the context of the complex interplay between the cardiac and renal systems. A rationale for improving recognition and treatment of congestion is also proposed.

Thiazide-type diuretics have been recommended for initial treatment of hypertension in most patients, but should this recommendation differ for patients with and without coronary heart disease (CHD)? The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a randomized, double-blind hypertension treatment trial in 42,418 participants with high risk of combined cardiovascular disease (CVD) (25% with preexisting CHD). This post hoc analysis compares long-term major clinical outcomes in those assigned amlodipine (n = 9048) or lisinopril (n = 9,054) with those assigned chlorthalidone (n = 15,255), stratified by CHD status. After 4 to 8 years, randomized treatment was discontinued. Total follow-up (active treatment + passive surveillance using national databases for deaths and hospitalizations) was 8 to 13 years. For most CVD outcomes, end-stage renal disease, and total mortality, there were no differences across randomized treatment arms regardless of baseline CHD status. In-trial rates of CVD were significantly higher for lisinopril compared with chlorthalidone, and rates of heart failure were significantly higher for amlodipine compared with chlorthalidone in those with and without CHD (overall hazard ratios [HRs] 1.10, p

Measurement error in assessment of sodium and potassium intake obscures associations with health outcomes. The level of this error in a diverse US Hispanic/Latino population is unknown. We investigated the measurement error in self-reported dietary intake of sodium and potassium and examined differences by background (Central American, Cuban, Dominican, Mexican, Puerto Rican and South American). In 2010-2012, we studied 447 participants aged 18-74 years from four communities (Miami, Bronx, Chicago and San Diego), obtaining objective 24-h urinary sodium and potassium excretion measures. Self-report was captured from two interviewer-administered 24-h dietary recalls. Twenty percent of the sample repeated the study. We examined bias in self-reported sodium and potassium from diet and the association of mismeasurement with participant characteristics. Linear regression relating self-report with objective measures was used to develop calibration equations. Self-report underestimated sodium intake by 19.8% and 20.8% and potassium intake by 1.3% and 4.6% in men and women, respectively. Sodium intake underestimation varied by Hispanic/Latino background (P

In 2013, an Institute of Medicine (IOM) Committee, after reviewing available evidence, reached conclusions that differed importantly from conventional belief.1 They reported that while harm exists with “excessive” sodium intakes, the term was specifically left undefined. In addition, they concluded, “evidence was insufficient to support (or refute) previous recommendations for population-based efforts to achieve sodium intake levels of less than 2.3 g/day in the general population or most population subgroups.” While recognizing that blood pressure was a strong surrogate for cardiovascular events, IOM nevertheless concluded that the health effect of of dietary sodium should be determined through assessment of evidence directly linking sodium intake to actual health outcomes—and not through intermediate variables such as blood pressure. Since the IOM report, several additional publications linking dietary sodium to health outcomes have confirmed, clarified, and extended its conclusions.2–6 While observational studies can determine associations, they do not establish causality, and can not generally be a basis for therapeutic intervention. The purpose of this review is to critically assess these recent reports in the context of already available evidence, as well as the IOM report, and to suggest policy options consistent with the evidence. Post IoM studIes

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a randomized, double-blind, practice-based, active-control, comparative effectiveness trial in 33,357 high-risk hypertensive participants. ALLHAT compared cardiovascular disease outcomes in participants initially treated with an angiotensin-converting enzyme inhibitor (lisinopril), a calcium channel blocker (amlodipine), or a thiazide-type diuretic (chlorthalidone). We report stroke outcomes in 1517 participants in-trial and 1596 additional participants during post-trial passive surveillance, for a total follow-up of 8-13 years. Stroke rates were higher with lisinopril (6-year rate/100 = 6.4) than with chlorthalidone (5.8) or amlodipine (5.5) in-trial but not including post-trial (10-year rates/100 = 13.2 [chlorthalidone], 13.1[amlodipine], and 13.7 [lisinopril]). In-trial differences were driven by race (race-by-lisinopril/chlorthalidone interaction P = .005, race-by-amlodipine/lisinopril interaction P = .012) and gender (gender-by-lisinopril/amlodipine interaction P = .041), separately. No treatment differences overall, or by race or gender, were detected over the 10-year period. No differences appeared among treatment groups in adjusted risk of all-cause mortality including post-trial for participants with nonfatal in-trial strokes. Among Blacks and women, lisinopril was less effective in preventing stroke in-trial than either chlorthalidone or amlodipine, even after adjusting for differences in systolic blood pressure. These differences abated by the end of the post-trial period.

Background: A paradoxical pressor systolic response to initial antihypertensive monotherapy has been observed in 8% of hypertensive patients. The long-term consequences of this finding are unknown. Methods: We included 945 hypertensive patients with baseline systolic blood pressure (SBP) ≥140mm Hg. A 4-week washout period free of antihypertensive drugs was allowed for those already on treatment at entry. Mortality outcomes were ascertained from the National Death Index. Subjects were categorized by SBP response into depressor (≥10mm Hg fall), nonresponder, and pressor (≥10mm Hg rise) categories. Results: There were 268 fatalities. Of these, 100 (37%) were from cardiovascular disease (CVD), of which 70 (70%) were due to coronary artery disease (CAD). A pressor response was associated with higher SBP at 1 year compared with the nonresponder or depressor response (141 vs. 136 vs. 136mm Hg). CVD mortality was greater in pressors than depressors (hazard ratio (HR) = 3.0; 95% confidence interval (CI) = 1.4-6.4; P = 0.004], as was CAD (HR = 3.1; 95% CI = 1.4-6.8; P < 0.01) and all-cause mortality (HR = 1.7; 95% CI = 1.1-2.6; P = 0.02), after adjusting for 1-year SBP and other possible confounders. Conclusions: We found the incidence of a pressor response to monotherapy at 3 months was significantly, specifically, and independently associated with higher subsequent cardiovascular mortality.

Background The effect of sodium intake on population health remains controversial. The objective was to investigate the incidence of all-cause mortality (ACM) and cardiovascular disease events (CVDEs) in populations exposed to dietary intakes of low sodium ( 215 mmol). Methods The relationship between individual measures of dietary sodium intake vs. outcome in cohort studies and randomized controlled trials (RCTs) measured as hazard ratios (HRs) were integrated in meta-analyses. Results No RCTs in healthy population samples were identified. Data from 23 cohort studies and 2 follow-up studies of RCTs (n = 274,683) showed that the risks of ACM and CVDEs were decreased in usual sodium vs. low sodium intake (ACM: HR = 0.91, 95% confidence interval (CI) = 0.82-0.99; CVDEs: HR = 0.90, 95% CI = 0.82-0.99) and increased in high sodium vs. usual sodium intake (ACM: HR = 1.16, 95% CI = 1.03-1.30; CVDEs: HR = 1.12, 95% CI = 1.02-1.24). In population representative samples adjusted for multiple confounders, the HR for ACM was consistently decreased in usual sodium vs. low sodium intake (HR = 0.86; 95% CI = 0.81-0.92), but not increased in high sodium vs. usual sodium intake (HR = 1.04; 95% CI = 0.91-1.18). Within the usual sodium intake range, the number of events was stable (high usual sodium vs. low usual sodium: HR = 0.98; 95% CI = 0.92-1.03). Conclusions Both low sodium intakes and high sodium intakes are associated with increased mortality, consistent with a U-shaped association between sodium intake and health outcomes.

The 2013 Institute of Medicine (IOM; now the National Academy of Medicine) Report: Sodium intake in populations recommended that “clinical trials might focus on examining the effects of a range of sodium levels on risk of cardiovascular events, stroke, and mortality among patients in controlled environments.”1 This recommendation was specific in 2 regards. It recommends a cardiovascular outcomes trial of dietary sodium reduction, and it recommends this be done in people in controlled environments. There are important reasons behind these specific recommendations. Despite the large body of data on the relationship between cardiovascular disease and dietary sodium from observational studies and the positive impact on blood pressure in randomized controlled clinical trials and current national guidelines recommending daily sodium intakes of ≤2300 mg/d, mean daily intake for Americans remains in the 3400 to 3500 mg/d range.2 Some scientists have questioned the justification for a reduced intake of dietary sodium.3 This disagreement within the scientific community has been reported in the lay press, leading both clinicians and some in the public to express uncertainty on the issue.4–6 The IOM is not alone in calling for an outcomes clinical trial on dietary sodium. The World Heart Federation, the European Society of Hypertension, and the European Public Health Association joined together to call for a definitive clinical trial of sodium restriction.7 Indeed, for years, leading voices in this area of research have noted the absence of evidence from an outcomes-based clinical trial and advocated for execution of such a trial. The reason this trial has not been accomplished can be seen in the second specificity of the IOM recommendations: that the trial be performed in “patients in controlled environments.” This statement recognizes the …

Objective:To examine prospectively the relationship of attained blood pressure levels to cardiovascular events and mortality in older women in the Women's Health Initiative Long Life Study (WHI-LLS).Design and method:Participants in the LLS are 7,875 women who are part of the WHI, who were over 70 y

Objective:Belief that a particular blood pressure (BP) can separate ‘hypertension’ from ‘normo-tension’ has transformed a ‘risk factor’ into a treatable condition. An arbitrary blood pressure threshold establishes the diagnosis and standardizes treatment provided by conventional medical caregivers.

Calcium channel-blockers (CCB) are an important class of medication useful in the treatment of hypertension. Several observational studies have suggested an association between CCB therapy and gastrointestinal hemorrhage. Using administrative databases, we re-examined in a post-hoc analysis whether the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants randomized to the calcium-channel blocker amlodipine had a greater risk of hospitalized gastrointestinal bleeding (a pre-specified outcome) compared to those randomized to the diuretic chlorthalidone or the ACE-inhibitor lisinopril. Participants randomized to chlorthalidone did not have a reduced risk for gastrointestinal bleeding hospitalizations compared to participants randomized to amlodipine (HR, 1.09, 95% CI 0.92-1.28). Those randomized to lisinopril were at increased risk of gastrointestinal bleeding compared those randomized to chlorthalidone (HR, 1.16; 95% CI, 1.00-1.36). In a post-hoc comparison, participants assigned lisinopril therapy had a higher risk of hospitalized gastrointestinal hemorrhage (HR,1.27, 95% CI 1.06-1.51) versus those assigned to amlodipine. In-study use of atenolol prior to first gastrointestinal hemorrhage was related to a lower incidence of GI bleeding (HR, 0.69; 95% CI, 0.57-0.83). In conclusion, hypertensive patients on amlodipine do not have an increased risk of GI bleeding hospitalizations compared to those on either chlorthalidone or lisinopril.

Background Four recent reports revealed differences in survival rates among treated cardiovascular patients taking renin-angiotensin system–blocking drugs. Patients with higher on-treatment plasma renin activity (PRA) levels died sooner of cardiovascular mortality than those with lower levels. We investigated whether excessive sodium depletion might have induced the higher PRA levels and contributed to the greater morbidity and mortality. Methods Using published data, ranges of PRA, blood pressures, drug usage, and biochemical parameters were compared among various groups of cardiovascular patients. Results We showed (i) that PRA levels are usually medium to low in treated cardiovascular patients, but are sometimes abnormally high, (ii) that excessive sodium depletion can induce such high PRA levels, (iii) that the higher PRA patients exhibited evidence of sodium depletion: lower blood pressures, more frequent natriuretic drug usage, lower N-terminal pro b-type natriuretic peptide (NT-proBNP), and higher blood urea nitrogen and uric acid levels, with similar usage of renin-angiotensin blocking drugs. Conclusions We hypothesize that patients with high on-treatment PRA levels die sooner of cardiovascular events because they are excessively sodiumvolume depleted. Moreover, renin-angiotensin system–blocking drugs may be harmful in such patients because they can functionally interfere with the effects of reactive rises in PRA that are triggered to prevent potentially dangerous falls in blood pressure, increases in plasma potassium, and falls in glomerular filtration rate. Careful liber alization of salt intake and subtraction of natriuretic drugs, sufficient to reduce reactive hyperreninemia without inducing unacceptable increases in blood pressure, might benefit such patients and decrease risk of adverse effects from drugs that block the renin-angiotensin system.

Concerns exist that diuretic-induced changes in serum potassium may have adverse effects in hypertensive patients. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, a large practice-based clinical trial, made it possible to examine consequences of observed changes in potassium during care in conventional practice settings. Normokalemic participants randomized to chlorthalidone (C) versus amlodipine or lisinopril as a first-step drug were stratified by year-1 potassium. Postyear-1 outcomes among hypokalemics (potassium, 5.4 mmol/L) were compared with normokalemics (potassium, 3.5–5.4 mmol/L). Year-1 hypokalemia incidence was 6.8%; incidence in C (12.9%) differed from amlodipine (2.1%; P P P P P

A randomized, double-blind, active-controlled, multicenter trial assigned 32,804 participants aged 55 years and older with hypertension and ≥ 1 other coronary heart disease risk factors to receive chlorthalidone (n=15,002), amlodipine (n=8898), or lisinopril (n=8904) for 4 to 8 years, when double-blinded therapy was discontinued. Passive surveillance continued for a total follow-up of 8 to 13 years using national administrative databases to ascertain deaths and hospitalizations. During the post-trial period, fatal outcomes and nonfatal outcomes were available for 98% and 65% of participants, respectively, due to lack of access to administrative databases for the remainder. This paper assesses whether mortality and morbidity differences persisted or new differences developed during the extended follow-up. Primary outcome was cardiovascular mortality and secondary outcomes were mortality, stroke, coronary heart disease, heart failure, cardiovascular disease, and end-stage renal disease. For the post-trial period, data are not available on medications or blood pressure levels. No significant differences (P

Background 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. methodS 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. reSult S 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. concluSionS 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.

Background We reported earlier that there was no decline of acute myocardial infarction hospitalization from 1988 to 1997. We now extend these observations to document trends in acute myocardial infarction hospitalization rates and in-hospital case-fatality rates for 27 years from 1979 to 2005. Methods We determined hospitalization rates for acute myocardial infarction by age and gender using data from the National Hospital Discharge Survey and US civilian population from 1979 to 2005, aggregated by 3-year groupings. We also assessed comorbid, complications, cardiac procedure use, and in-hospital case-fatality rates. Results Age-adjusted hospitalization rate for acute myocardial infarction identified by primary International Classification of Diseases code was 215 per 100,000 people in 1979-1981 and increased to 342 in 1985-1987. Thereafter, the rate stabilized for the next decade and then declined slowly after 1996 to 242 in 2003-2005. Trends were similar for men and women, although rates for men were almost twice that of women. Hospitalization rates increased substantially with age and were the highest among those aged 85 years or more. Although median hospital stay decreased from 12 to 4 days, intensity of hospital care increased, including use of coronary angioplasty, coronary bypass, and thrombolytics therapy. During the period, reported comorbidity from diabetes and hypertension increased. Acute myocardial infarction complicated by heart failure increased, and cardiogenic shock decreased. Altogether, the in-hospital case-fatality rate declined. Conclusion During the past quarter century, hospitalization for acute myocardial infarction increased until the mid-1990s, but has declined since then. At the same time, in-hospital case-fatality rates declined steadily. This decline has been associated with more aggressive therapeutic intervention.

OBJECTIVE Although statin therapy reduces cardiovascular risk, its relationship with the development of diabetes is controversial. The first study (West of Scotland Coronary Prevention Study [WOSCOPS]) that evaluated this association reported a small protective effect but used nonstandardized criteria for diabetes diagnosis. However, results from subsequent hypothesis-testing trials have been inconsistent. The aim of this meta-analysis is to evaluate the possible effect of statin therapy on incident diabetes. RESEARCH DESIGN AND METHODS A systematic literature search for randomized statin trials that reported data on diabetes through February 2009 was conducted using specific search terms. In addition to the hypothesis-generating data from WOSCOPS, hypothesis-testing data were available from the Heart Protection Study (HPS), the Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) Study, the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT), the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER), and the Controlled Rosuvastatin Multinational Study in Heart Failure (CORONA), together including 57,593 patients with mean follow-up of 3.9 years during which 2,082 incident diabetes cases accrued. Weighted averages were reported as risk ratios (RRs) with 95% CIs using a random-effects model. Statistical heterogeneity scores were assessed with the Q and I2 statistic. RESULTS In the meta-analysis of the hypothesis-testing trials, we observed a small increase in diabetes risk (RR 1.13 [95% CI 1.03–1.23]) with no evidence of heterogeneity across trials. However, this estimate was attenuated and no longer significant when the hypothesis-generating trial WOSCOPS was included (1.06 [0.93–1.25]) and also resulted in significant heterogeneity (Q 11.8 [5 d.f.], P = 0.03, I2 = 57.7%). CONCLUSIONS Although statin therapy greatly lowers vascular risk, including among those with and at risk for diabetes, the relationship of statin therapy to incident diabetes remains uncertain. Future statin trials should be designed to formally address this issue.

The idea for a workshop focused on sodium and health was generated by the editors of the American Journal of Hypertension and the Chinese Journal of Hypertension as part of their emerging collaboration. It reflects a belief that scientists and clinicians interested in blood pressure and its related conditions would profit from more effective communication and interaction. Salt was chosen as a central topic because of its multiple physiological and pathological effects, its importance to human health, its role in elevating blood pressure, the unresolved scientific issues, and the absence of an agreed public health response regarding dietary sodium. In addition, much current clinical and population research has begun to shed light on how the interaction of genetics, environment, and diet determines the impact of sodium intake on human health and disease. Surprisingly, given the often passionate professional interest, there has been no regular forum dedicated to an exchange of new knowledge and current research findings. The biomedical literature provides strong evidence that investigators around the world are generating important new findings that increase understanding of how dietary sodium may relate to both health and disease. Given the widely shared need and interest, the workshop's organizers hope that the experience in Xi'an will lead to the appearance of regular working meetings on sodium and human disease on the international scientific schedule. The ultimate goal is for this scientific discourse to lead to evidence-based programs for population salt consumption that will contribute to the betterment of human health.

Nutrition Reviews has had a continuing interest in the scientific basis of arguments for and against health claims on foods. Such claims were first authorized by the Food and Drug Administration (FDA) in 1993 under the terms of the Nutrition Labelling and Education Act of the U.S. Congress, passed in 1990. Since then there have been petitions that have resulted in a newly authorized claim for oats and other petitions directed toward modification or deletion of the originally approved claims. The Salt Institute, an industry-supported organization, has actively participated in the discussions regarding the sodium and hypertension health claim. The scientists signing this statement are familiar with the evolving understanding of the relationship between sodium and hypertension. The statement reviews more recent studies and critiques the arguments for a sodium health claim. We invite our readers to respond to the discussion in this controversial area of nutrition science and policy.

BACKGROUND Uncontrolled hypertension is a common and important risk factor for heart disease and stroke. Nevertheless, the control rate among patients taking prescribed medication and/or therapeutic lifestyle modification has remained about the same for the past several decades. METHODS We analyzed 2003 and 2004 National Ambulatory Medical Care Survey (NAMCS) data to determine hypertension control in the physician offices in the United States. All visits for hypertension with measured blood pressure levels were included in the analyses. Survey weights were applied to obtain national estimates. Characteristics associated with hypertension control status were identified. RESULTS About 176 million hypertension-related office visits occurred (9.7% of total office visits) during 2003 and 2004. Of these, 17, 44, and 62% of visits had blood pressure

Diabetes mellitus is a powerful risk factor for cardiovascular disease (CVD), and most persons with diabetes ultimately succumb to coronary artery disease or stroke. The coincidence of hypertension and diabetes is common and, over the long term, sharply increases cardiovascular risk. The incidence of diabetes (new-onset diabetes [NOD]) among hypertensive persons is high, and appears to be increased during antihypertensive therapy. NOD is a distressing clinical event, provoking psychological distress, more clinical testing, and, sometimes, the need for hypoglycaemic therapy. Diuretics and β-blockers are more likely to provoke NOD than other drugs that block the renin angiotensin system, or calcium channel blocking agents, It is important to note that the alternative agents have not been shown to prevent the emergence of hyperglycaemia, but seem to be metabolically neutral. It is also true that because diuretic-induced NOD may be due to hypokalaemia, it can sometimes be reversed without sacrificing diuretic therapy. The evidence suggests that most NOD appearing during antihypertensive therapy is not drug induced, but rather part of the natural history of disease. Since diabetes is such a powerful CVD risk factor, it can hardly be surprising that, over the long term, NOD is associated with increased CVD. However, there is no evidence in short-term clinical trials that diuretic-induced NOD increases CVD or detracts from the cardioprotective effects of these agents. Indeed, long-term follow-up of participants in a large placebo-controlled trial of diuretic therapy in elderly hypertensive subjects suggests that this antihypertensive therapy actually eliminates the expected increase in CVD. In summary, although NOD can hardly be dismissed as a trivial event, concern about its possible occurrence is not a reason to influence initial antihypertensive drug selection, nor does its appearance provide a reason to compromise antihypertensive therapy. Indeed, the available evidence suggests that blood pressure control trumps hypoglycaemic therapy as the very best tool for CVD prevention in new or established diabetic subjects.

Background: We examined the prevalence of cardiac and cerebrovascular disease among hospitalized patients with and without multiple sclerosis (MS). Methods: This study used the Statewide Planning and Research Cooperate System data set of over 15 million hospitalizations in New York City from 1988 through 2002. We identified MS patients 40–84 years of age who were hospitalized for reasons other than MS or related complications. MS patients were matched 1:2 on age, gender, race/ethnicity, and insurance. Outcomes included a principal discharge diagnosis of ischemic heart disease [International Classification of Diseases, Ninth Revision (ICD-9) 410–414], myocardial infarction (ICD-9 410), and ischemic stroke (ICD-9 434, 436). Multivariate logistic regression was used to compare vascular disease outcomes in MS and non-MS patients controlling for demographic and clinical factors. Results: Our studyincluded 9,949 hospitalizations among MS patients and 19,898 hospitalizations for matched non-MS controls. MS patients were less likely to be hospitalized for ischemic heart disease (OR = 0.58, 95% CI = 0.51–0.66) or myocardial infarction (OR = 0.78, 95% CI = 0.64–0.96), but more likely to be hospitalized for ischemic stroke (OR = 1.66, 95% CI = 1.33–2.09) than matched non-MS controls. Conclusion: MS patients have decreased rates of hospital admission for ischemic heart disease and myocardial infarction, but increased rates of hospitalization for ischemic stroke as compared to the general non-MS population.

Hippocrates would not be surprised to read that persons with gout had higher mortality, and particularly cardiovascular-related mortality, than persons without gout.1 On the other hand, he might well have been bemused, nearly 2500 years after he described the syndrome, that this made news. Article p 894 He should not have been. All too often, rigorous examination debunks conventional wisdom. Reassuringly, in this case, Drs Choi and Curhan found evidence to support long-standing belief. These dedicated and productive students of the pathogenesis and natural history of gout have here reported empiric data from the 51 000 male nonphysician health professionals who participated in the Health Professions Follow-up Study. From initial examination in 1986 through nearly 600 000 person-years of follow-up, 5825 deaths occurred, of which 2132 were cardiovascular and 1576 were ascribed to coronary heart disease, rates that attest to the generally good health of the group. The ≈6% prevalence of gout, at baseline, in men in their mid-50s, who mirror the general US population in body mass index, reported history of hypertension, hypercholesterolemia, and diabetes mellitus, was higher than expected. Interim biennial questionnaires identified incident cases of gout. Participants with gout were both more likely to report coronary heart disease (CHD) at baseline and, regardless of CHD status, more likely than gout-free persons to have cardiovascular disease (CVD) risk factors. Results were presented after stratification by CHD status at baseline. As expected, the incidence of all-cause and CHD mortality was much greater in those with than in those without prevalent CHD. The adjusted increased relative risk of those with gout (compared with those without) for all-cause, CVD, and CHD mortality was ≈25%. The single exception was a near doubling of increased relative risk of CHD mortality among those free of CHD at baseline. Neither the inclusion of incident …

Cardiovascular disease (CVD) is the leading cause of the growing global disease burden due to non-communicable diseases. For successful prevention and control of CVD, strategies that focus on individuals need to complement population-wide strategies. Strategies that focus on individuals are cost effective only when targeted at high-risk groups. Risk prediction tools that easily and accurately predict an individual's absolute risk of CVD are key to targeting limited resources at high-risk individuals who are likely to benefit the most. Health systems in low-income countries do not have the basic infrastructure facilities to support resource-intensive risk prediction tools, particularly in primary healthcare. The WHO/ISH charts presented here, enable the prediction of future risk of heart attacks and strokes in people living in low and middle income countries, for the first time. Furthermore, since the charts use simple variables they can be applied even in low resource settings. Thus the WHO/ISH risk predication charts and the accompanying guideline will improve the effectiveness of cardiovascular risk management even in settings which do not have sophisticated technology.

PURPOSE OF REVIEW Persistent recommendations for universal restriction of dietary sodium intake are based on associations of sodium intake with blood pressure. No clinical trial data support an association of sodium intake with mortality and morbidity outcomes, however, while results of observational studies appear heterogeneous. Can these contradictory data be reconciled to inform health policy regarding sodium intake recommendations? RECENT FINDINGS We reported (2006) a statistically significant (P = 0.03) association of sodium intake less than 2.3 g/day with increased cardiovascular disease mortality (hazard ratio 1.37) in a representative sample of the US adult population with an observed baseline mean sodium intake of 2.7 g/day. Others reported (2004) a significant (P < 0.01) higher stroke death among males and borderline significant (P = 0.07) for females, for highest compared with lowest sodium tertile in a community in Japan with mean intake of 5.4 g/day. SUMMARY These results are consistent with earlier studies suggesting that the association of sodium with morbidity and mortality in industrial societies follows a 'J shape' with a direct association at high levels of average intake (over 4 g), an inverse association at lower levels (less than 2 g) and no measurable effect for the widely prevalent intakes in between.

Background and Purpose: While age-adjusted stroke mortality in the United States has declined consistently during the last century, trends in stroke incidence and hospitalization are less known. This study examines trends in stroke hospitalization from 1988 to 2004. Methods: Stroke hospitalizations were estimated from the annual National Hospital Discharge Survey, 1988–2004. Stroke was defined as a first-listed diagnosis of ICD-9-CM (International Classification of Diseases, 9th Revision, Clinical Modification) code 430–434 or 436–438. Trends in hospitalization rates were compared for groups defined by selected patient characteristics. Results: Stroke hospitalizations totaled 603,000 in 1988, peaked at 833,000 in 1997, then declined to 726,000 in 2004, a figure still higher than in 1988. Age-adjusted stroke hospitalization rates for men (per 100,000 population) increased from 287 in 1988 to 352 in 1997, but declined to 265 in 2004, and for women, rates were 252, 293 and 223 in the corresponding years. The majority of stroke hospitalizations in 2004 occurred at ages ≧65 years (69% in men and 78% in women). Decline in rates after 1997 occurred at ages 65–74 and ≧75 years. In 2004, 64% of strokes were classified as ischemic, 16% as hemorrhagic and 16% as ill-defined. Decline in hospitalization rates after 1997 were observed for ischemic and ill-defined, but not for hemorrhagic stroke. Between 1988 and 2004, the reporting of hypertension, diabetes and coronary heart disease as secondary diagnoses among stroke hospitalizations increased. Conclusions: Decline in stroke hospitalizations since 1997 was observed among men and women >65 years, who suffered ischemic or ill-defined stroke. Although long-term observation is needed to confirm this finding, the decline in stroke hospitalizations after 1997 suggests treatment of hypertension may have resulted in stroke prevention.

Dear Editor: The comments and concerns expressed by Thornton (1) relate to our recent reviews from the ASN Scientific Sessions at Experimental Biology 2014 symposium regarding sodium intake and health outcomes. His comments appropriately expand the discussion of whether to reduce sodium intakes to low amounts. Our intent with the cited papers was never to exclude critical cofactors such as water. The neural regulation of water and sodium are physiologically interrelated (2), because optimizing both volume and osmolality are essential elements of cardiovascular health. As noted by Thornton, the hormonal response to decreased perfusion invokes angiotensin II, aldosterone, and vasopressin release, all of which have potent vascular actions that potentially increase cardiovascular disease (CVD) risk. Thornton’s argument that overlooking the role of water intake in understanding the association of sodium with health outcomes raises another question as to the safety of a health policy directed at lowering sodium intake across the entire population. Hyponatremia at hospital admission and in free-living populations has been associated with both increased morbidity and mortality (3–6). Those findings are consistent with the proposition that sodium and water intake must be considered in tandem when assessing health outcomes. As opposed to previous hypotheses that comorbidities accounted for an increased risk of death, recent data indicate that the greatest risk appears in those with few comorbid conditions (5, 6). Hyponatremia is the most common electrolyte disturbance in the general population (6). Reduced sodium intake in and of itself can impair the healthy kidney’s ability to excrete excess free water (7). Therefore, a lower sodium diet would promote the development of a reduced serum sodium concentration, or hyponatremia. Although it is typically assumed that with normal kidney function there is a large excess renal capacity to excrete water, what is not generally appreciated is that reduced solute intake impairs the healthy kidney’s capacity to excrete excess water (7). Sodium intake is one of the principle contributors to the renal solute load. Thus, lower sodium intake potentially sets in motion a normal physiologic response that would contribute to the development of hyponatremia in a segment of the general population. If healthy persons lower their sodium intake as recommended by current guidelines, but maintain water consumption that exceeds requirements (as is widely promoted to the general population, especially physically active people), those guidelines may well set the stage for the emergence of hyponatremia even in otherwise healthy people. The hyponatremia-related mortality and morbidity data published to date and the physiology of sodium and water handling by the kidney provide a plausible explanation to account for the increased risk of death from lower sodium intake in healthy, low-risk individuals (8). Furthermore, such a risk would not solely rest on activation of the renin-angiotensin system and aldosterone invoked for those already at risk of CVD. Perhaps the simplest and most important aspect of the issue raised by Thornton is his reminder that water metabolism is linked to sodium. That obvious and accepted physiologic link should serve as a note of caution that there are many “moving parts” associated with reducing sodium intake in the general population. The longstanding assumption that sodium restriction to amounts below that normally consumed in modern societies is safe and effective fails to consider that complex physiology. The old adage that “it is too good to be true” may well apply to the simplistic policy view that sodium restriction lowers blood pressure and therefore reduces CVD risk.

Acute myocardial infarction (AMI) complicated by cardiogenic shock is associated with high morbidity and mortality.Using the National Hospital Discharge Survey data from 1979 to 2003, we measured trends in the incidence of AMI complicated by cardiogenic shock, the use of percutaneous transluminal coronary angioplasty (PTCA), and the inhospital death.Age-adjusted hospitalization rates (per 100,000 populations) in 1979 and 2003, respectively, were 213 and 261 for AMI, and 8.6 and 4.3 for AMI complicated by cardiogenic shock. Among patients with AMI, the proportion with cardiogenic shock was 3.9% (n = 17,000) in 1979 and 1.7% (n = 13,000) in 2003. Patients with acute myocardial infarction with cardiogenic shock, compared with those without cardiogenic shock, were more likely to be women (48% vs 43%, P.0001), more likely to have anterior wall AMI (33% vs 14%, P.0001), and had much higher inhospital mortality (43% vs 7%, P.0001). Over the years, among AMI complicated by cardiogenic shock, PTCA use increased substantially from 0% to 28%. During this period, inhospital death decreased from 84% to 43%. After adjustment for age, sex, location of AMI, health insurance, and survey year, PTCA use was significantly associated with decreased inhospital deaths among patients with AMI with cardiogenic shock.Although hospitalization for AMI has increased over the past 25 years, the hospitalization rate of AMI complicated by cardiogenic shock has decreased by 50%. At the same time, PTCA use and hospital survival have increased substantially among cardiogenic shock patients.

Representatives from five international organizations (International Society of Nephrology, World Heart Federation, International Diabetes Federation, International Atherosclerosis Federation, and International Society of Hypertension) participated in a strategic planning workshop in December 2005 in Bellagio, Italy sponsored by the Rockefeller Foundation. There were equal representatives from developed and developing countries. Global perspectives on diabetes and cardiovascular and renal diseases were presented, with special emphasis on China, India, Latin America, and Africa. The rationale and effectiveness of preventive measures were discussed. It was apparent that measures for primary prevention and early intervention for all the chronic vascular diseases are similar. The five organizations agreed that an integrated global approach to chronic vascular diseases is needed. They resolved to collaborate and work towards an integrated approach to chronic vascular diseases with the establishment of a 5-year plan for the prevention and treatment of chronic vascular diseases, including public advocacy, advising international and national agencies, and improving education and the practice of established approaches.

The Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial (ALLHAT) provides a unique opportunity to compare the long-term relative safety and efficacy of angiotensin-converting enzyme inhibitor and calcium channel blocker–initiated therapy in older hypertensive individuals. Patients were randomized to amlodipine (n=9048) or lisinopril (n=9054). The primary outcome was combined fatal coronary heart disease or nonfatal myocardial infarction, analyzed by intention-to-treat. Secondary outcomes included all-cause mortality, stroke, combined cardiovascular disease (CVD), end-stage renal disease (ESRD), cancer, and gastrointestinal bleeding. Mean follow-up was 4.9 years. Blood pressure control was similar in nonblacks, but not in blacks. No significant differences were found between treatment groups for the primary outcome, all-cause mortality, ESRD, or cancer. Stroke rates were higher on lisinopril in blacks (RR=1.51, 95% CI 1.22 to 1.86) but not in nonblacks (RR=1.07, 95% CI 0.89 to 1.28), and in women (RR=1.45, 95% CI 1.17 to 1.79), but not in men (RR=1.10, 95% CI 0.92 to 1.31). Rates of combined CVD were higher (RR=1.06, 95% CI 1.00 to 1.12) because of higher rates for strokes, peripheral arterial disease, and angina, which were partly offset by lower rates for heart failure (RR=0.87, 95% CI 0.78 to 0.96) on lisinopril compared with amlodipine. Gastrointestinal bleeds and angioedema were higher on lisinopril. Patients with and without baseline coronary heart disease showed similar outcome patterns. We conclude that in hypertensive patients, the risks for coronary events are similar, but for stroke, combined CVD, gastrointestinal bleeding, and angioedema are higher and for heart failure are lower for lisinopril-based compared with amlodipine-based therapy. Some, but not all, of these differences may be explained by less effective blood pressure control in the lisinopril arm.

The expectation that dietary sodium intake might influence cardiovascular disease occurrence has been based upon its impact on blood pressure (BP). Solid experimental data confirms the ability of large (75-100 mmols/24 hours) changes in dietary sodium to reduce pressure by, on average, mid-low single digits. However, there is substantial inter-individual variation in BP response. In addition, sodium restriction generates other, sometimes undesirable effects, including increased insulin resistance, activation of the renin-angiotensin system, and increased sympathetic nerve activity. The health effects of salt restriction are, therefore, the sum of these recognized, and probably other unrecognized, intermediate effects. Ideally, salt restriction would be tested in a randomized clinical trial. In its absence, there are 9 observational studies linking baseline sodium intake, estimated by either 24 hour urine or dietary intake, to morbidity and mortality. The results have been inconsistent. The only study in hypertensive patients, there was an inverse relation of sodium to cardiovascular outcome. In a Japanese study, stroke incidence was increased among males with the highest salt intake. Two studies found a direct relation of sodium intake to cardiovascular mortality in an obese minority of the group studied. Taken together, these results suggest, not surprisingly given the genetic, behavioral, and environmental variety of humankind, that heterogeneity best describes the relation of sodium intake to cardiovascular morbidity and mortality. In short, the available data provides no support for any universal recommendation of a particular level of dietary sodium.

Worldwide increases in obesity and diabetes have aroused concern that increased morbidity and mortality will follow. The objective here is to determine the trend of diabetes-related morbidity and mortality in New York, New York. Using New York death certificate data for 1989–1991 and 1999–2001 and hospital discharge data for 1988–2002, we measured all-cause and cause-specific mortality in 1990 and 2000, as well as annual hospitalization rates for diabetes and its complications among patients hospitalized with acute myocardial infarction and/or diabetes. During this decade, all-cause and cause-specific mortality rates declined, with the striking exception of diabetes, which increased 61 and 52% for men and women, respectively, as did hospitalization rates for diabetes and its complications. The percentage of all acute myocardial infarctions occurring in patients with diabetes increased from 21 to 36%, and the absolute number doubled from 2,951 to 6,048. Although hospital days due to acute myocardial infarction fell overall, for those with diabetes, they increased 51% (from 34,188 to 51,566). These data document a marked upsurge in diabetes-related mortality and morbidity in New York City, including a sharp increase in diabetic patients hospitalized for myocardial infarction. If continued, this threatens the long-established nationwide trend to reduced coronary artery disease events.

Objective While recent studies indicate that renal dysfunction may be predictive of all-cause mortality and cardiovascular disease (CVD) outcomes in hypertensive individuals, there has been little attention to the specific association of ischemic heart disease (IHD) mortality and renal function. This study examines the relationship between IHD mortality and baseline glomerular filtration rate (GFR) (estimated by the Cockcroft and Gault formula) among treated hypertensive subjects. Design A prospective cohort study of participants in a worksite-based antihypertensive treatment program in New York City (1981–1999). Patients We studied 9929 subjects who had at least 6 months follow-up (mean 9.6 years) with a baseline serum creatinine. Main outcome measures IHD death outcomes (n = 343) ascertained from the National Death Index. Results Multivariate Cox proportional hazard models were constructed adjusting for known cardiovascular risk factors. Mean GFR of the cohort was 91.6 ml/min per 1.73 m2. Those with lower GFR were more likely to be older, female, White, report a history of cardiovascular disease, have higher cholesterol and blood urea nitrogen values, and lower hemoglobin and body mass index than those with highest GFR. After adjustment for known cardiovascular risk factors, the risk of IHD death increased progressively as the GFR decreased. Hazard ratio for IHD mortality for each 10-unit reduction of estimated GFR below the normal threshold of ≥ 90 ml/min per 1.73 m2 was 1.33 (95% confidence interval 1.17, 1.50; P Conclusions The results of this study suggest an independent inverse association between estimated GFR and IHD mortality among treated hypertensive individuals.

A favorable effect of exercise on cardiovascular longevity has been repeatedly demonstrated in the general population. The association of exercise and cardiovascular disease (CVD) outcome among persons with different blood pressure (BP) status is less well known.We examined the epidemiologic follow-up of the First National Health and Nutrition Examination Survey (NHANES I) (1971-1992). Of 14,407 participants, 9791 subjects aged 25 to 74 years met inclusion criteria. All cause, CVD, and non-CVD mortality rates, as well as CVD incidence rates were determined. The associations of levels of exercise and outcomes by BP status were examined. Age- and gender-adjusted rates, as well as Cox proportional hazard models were determined.During 17 years of follow-up, there were 3069 deaths, 1465 of which were CVD. In addition, 2808 subjects had incident CVD events. Overall, CVD incidence and mortality rates increased as BP rose. The association of exercise with CVD events differed by BP status (normal, prehypertension, and hypertension). Age- and gender-adjusted CVD mortality rate per 1000 person-years for least, moderate, and most exercise were 5.0, 3.6, and 2.4 among normotensive subjects (P.05), 6.3, 4.7, and 5.2 among prehypertensive subjects (P.05), and 11.8, 9.8, and 8.7 among hypertensive subjects (P.01), respectively. In fact, exercise was a significant independent predictor of reduced CVD event only among hypertensive subjects, after adjusting for other CVD risk factors. Among prehypertensive and normotensive subjects, where events were fewer, those who exercise more vigorously also had lower mortality, but these differences did not reach statistical significance.This study, consistent with previous observational data, demonstrates that increased exercise is associated with decreased CVD event. Interestingly, this effect is most robust among hypertensive subjects, whereas for prehypertensive and normotensive subjects, a significant benefit of exercise on CVD outcome, perhaps because of lack of power, was not found.

This study tests the hypothesis that high brachial pulse pressure might constitute preclinical cardiovascular disease, rather than a risk factor. We studied 1250 subjects (472 nonobese normotensive [63 mm Hg, and peripheral resistance high when >90th percentile of normal distribution. Among hypertensive subjects, 34% had high resistance; among them, 33% had high brachial pulse pressure, as opposed to 147 of 516 patients (28.5%) with normal resistance ( P =not significant). After adjusting for age, sex, race, body mass index, heart rate, and center, left ventricular (LV) internal dimension and mass were lower with high resistance, and higher when brachial pulse pressure was high. PP/SV was 36% higher with high resistance than with normal resistance, and higher when brachial pulse pressure was high (all P

The recent Institute of Medicine (IOM) report “Sodium intake in populations: Assessment of Evidence”1 has provided critical information concerning the dietary sodium guidelines currently recommended by agencies of the US government.2 The American Journal of Hypertension has assembled a set of commentaries providing the range of official and independent views addressing how the IOM report will (or should) influence dietary sodium policy and practice.3–7 Our purpose is to provide a concise and comprehensive assessment of how things stand in the immediate aftermath of the IOM report. Our hope is that these manuscripts will further inform what promises to be a lively public and scientific debate about the implications of the IOM report. The balanced review and analysis has the credibility to make this report a paradigm shifting publication. The hypothesis from which sodium guidelines emerged i.e., that because reduced sodium intake lowered blood pressure, it would inevitably prevent cardiovascular morbidity and mortality – has failed to find support in the IOM report. The Committee found that the modest blood pressure effect is not a certain surrogate for health outcomes associated with sodium intake. Instead, the Committee’s case rested upon evidence of actual health consequences associated with reducing sodium intake from the current average of 3,400 mgs/day, to 5,000 mgs) of sodium to all lower intake levels. Third, based upon the large body of mostly observational data reported over the past 8 years, it found that a possibility of harm existed at the lower (

Background Most current clinical guidelines focus primarily on the management of individual cardiovascular risk factors, such as high blood pressure (BP), hypercholesterolemia, or diabetes. A more appropriate clinical approach to reducing cardiovascular disease risk would be based on a comprehensive evaluation of risk profile, and accurate stratification of global (absolute) risk in individual patients. We propose that global risk should be used as the main determinant of whom to treat, how to treat, and how much to treat. Methods In this article we use a series of case studies to demonstrate the implications of replacing the traditional “single risk factor-based” approach to managing hypertension by one based on global risk assessment. In some situations patients with mildly elevated BP levels would not be recommended for antihypertensive drug treatment whereas others with lower BP would be treated, depending upon the entire risk profile. Conclusion We propose to replace the single risk factor-based approach with the assessment of global cardiovascular risk, both in the clinical management of individual patients and in guidelines.

Elevated cholesterol and glucose are known independent risk factors for coronary heart disease. This study examines whether an adverse synergistic interaction of cholesterol and glucose magnifies coronary heart disease risk among treated hypertensive patients. Subjects were hypertensive patients (n=6672) in a worksite treatment program, with entry fasting glucose P =0.009) improved a Cox proportional hazards model, adjusting for total cholesterol, fasting glucose, and other coronary heart disease risk factors. Adjusted hazard ratios for 3 upper total cholesterol categories (with total cholesterol

The impact of serum uric acid on cardiovascular outcomes in the LIFE study.BackgroundThe Losartan Intervention For Endpoint reduction in hypertension (LIFE) study demonstrated the superiority of a losartan-based regimen over atenolol-based regimen for reduction of cardiovascular (CV) morbidity and mortality. It has been suggested that the LIFE study results may be related to the effects of losartan on serum uric acid (SUA). SUA has been proposed as an independent risk factor for CV morbidity and death.MethodsCox regression analysis was used to assess relationship of SUA and treatment regimens with the LIFE primary composite outcome (CV death, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke).ResultsBaseline SUA was significantly associated with increased CV events [hazard ratio (HR) 1.024 (95% CI 1.017–1.032) per 10 μmol/L, P < 0.0001] in the entire study population. The association was significant in women [HR = 1.025 (1.013–1.037), P < 0.0001], but not in men [HR = 1.009 (0.998–1.019), P = 0.108]. After adjustment for Framingham risk score (FRS), SUA was no longer significant in the entire study population [HR = 1.006 (0.998–1.014), P = 0.122] or in men [HR = 1.006 (0.995–1.017), P = 0.291], but was significant in women [HR = 1.013 (1–1.025), P = 0.0457]. The baseline-to-end-of-study increase in SUA (standard deviation, SD) was greater (P < 0.0001) in atenolol-treated subjects (44.4 ± 72.5 μmol/L) than in losartan-treated subjects (17.0 ± 69.8 μmol/L). SUA as a time-varying covariate was strongly associated with events (P < 0.0001) in the entire population. The contribution of SUA to the treatment effect of losartan on the primary composite end point was 29% (14%-107%), P = 0.004. The association between time-varying SUA and increased CV risk tended to be stronger in women (P < 0.0001) than in men (P = 0.0658), although the gender-outcome interaction was not significant (P = 0.079).ConclusionThe increase in SUA over 4.8years in the LIFE study was attenuated by losartan compared with atenolol treatment, appearing to explain 29% of the treatment effect on the primary composite end point. The association between SUA and events was stronger in women than in men with or without adjustment of FRS.

OBJECTIVES We report on a subanalysis of the effects of losartan and atenolol on cardiovascular events in black patients in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. BACKGROUND The LIFE study compared losartan-based to atenolol-based therapy in 9,193 hypertensive patients with left ventricular hypertrophy (LVH). Overall, the risk of the primary composite end point (cardiovascular death, stroke, myocardial infarction) was reduced by 13% (p = 0.021) with losartan, with similar blood pressure (BP) reduction in both treatment groups. There was a suggestion of interaction between ethnic background and treatment (p = 0.057). METHODS Exploratory analyses were performed that placed LIFE study patients into black (n = 533) and non-black (n = 8,660) categories, overall, and in the U.S. (African American [n = 523]; non-black [n = 1,184]). RESULTS A significant interaction existed between the dichotomized groups (black/non-black) and treatment (p = 0.005); a test for qualitative interaction was also significant (p = 0.016). The hazard ratio (losartan relative to atenolol) for the primary end point favored atenolol in black patients (1.666 [95% confidence interval (CI) 1.043 to 2.661]; p = 0.033) and favored losartan in non-blacks (0.829 [95% CI 0.733 to 0.938]; p = 0.003). In black patients, BP reduction was similar in both groups, and regression of electrocardiographic-LVH was greater with losartan. CONCLUSIONS Results of the subanalysis are sufficient to generate the hypothesis that black patients with hypertension and LVH might not respond as favorably to losartan-based treatment as non-black patients with respect to cardiovascular outcomes, and do not support a recommendation for losartan as a first-line treatment for this purpose. The subanalysis is limited by the relatively small number of events.

A substantial body of epidemiological and experimental evidence suggests that serum uric acid is an important, independent risk factor for cardiovascular and renal disease especially in patients with hypertension, heart failure, or diabetes. Elevated serum uric acid is highly predictive of mortality in patients with heart failure or coronary artery disease and of cardiovascular events in patients with diabetes. Further, patients with hypertension and hyperuricemia have a 3- to 5-fold increased risk of experiencing coronary artery disease or cerebrovascular disease compared with patients with normal uric acid levels. Although the mechanisms by which uric acid may play a pathogenetic role in cardiovascular disease is unclear, hyperuricemia is associated with deleterious effects on endothelial dysfunction, oxidative metabolism, platelet adhesiveness, hemorheology, and aggregation. Xanthine oxidase inhibitors (e.g., allopurinol) or a variety of uricosuric agents (e.g., probenecid, sulfinpyrazone, benzbromarone, and benziodarone) can lower elevated uric acid levels but it is unknown whether these agents reversibly impact cardiovascular outcomes. However, the findings of the recent LIFE study in patients with hypertension and left ventricular hypertrophy suggest the possibility that a treatment-induced decrease in serum uric acid may indeed attenuate cardiovascular risk. LIFE showed that approximately 29% (14% to 107%, p = 0.004) of the treatment benefit of a losartan-based versus atenolol-based therapy on the primary composite endpoint (death, myocardial infarction, or stroke) may be ascribed to differences in achieved serum uric acid levels. Overall, serum uric acid may be a powerful tool to help stratify risk for cardiovascular disease. At the very least, it should be carefully considered when evaluating overall cardiovascular risk.

Salt and BP have been linked for more than a century. Recent data indicate that, given free access to sodium, in most populations, intake is between 100 and 200 mmol/d, although individual variation is wide. There is good evidence that individual differences are influenced by genetics, environment, and behavior. There is also solid clinical trial data suggesting that substantial reduction in sodium intake (75 to 100 mmol/d) will, on average, lower diastolic pressure by approximately 1 mmHg and systolic by approximately 3 to 5 mmHg. In addition, there is good evidence that sodium restriction is accompanied by other hemodynamic and nonhemodynamic effects. The health effect of sodium restriction can be assessed only by outcome study in humans. The best available evidence in this regard derives from observational study. The several available studies in the general population are inconsistent and demonstrate heterogeneity across subgroups in the relation of sodium intake to cardiovascular morbidity and mortality. Only a single study has been reported in hypertensive patients that links baseline sodium, measured by 24-h urinary excretion, and subsequent cardiovascular outcomes. In that study, controlling for other risk factors, there was a significant, independent, inverse association of urinary sodium excretion and coronary morbidity and mortality. Indeed, an increase of 66 mmol/24 h was associated with a 36% reduction in events. Taken together, these data provide no support for the notion that either normotensive or hypertensive individuals should routinely decrease (or increase) dietary sodium intake.

The renin-angiotensin system (RAS) maintains hemodynamic integrity by modulating both volume and vasoconstriction through a cybernetic feedback control mechanism. In addition, angiotensin II, the active component of the RAS, can be vasculotoxic and, in hypertensive individuals, is associated with increased cardiovascular morbidity and mortality. The objective of this study was to determine the distribution and determinants of plasma renin activity (PRA) in a representative sample of hypertensive persons.We systematically measured PRA in 4170 untreated participants in a systematic work site-based, hypertension treatment program.In this multiethnic employed population, patients were classified as follows: low renin,0.65 ng/mL/h (30% of the sample); medium renin, 0.66 to 4.5 mg/mL/h (60%); or high renin,4.5 ng/mL/h (10%). Low renin patients were more likely to be African American, female, and slightly older. However, the majority of women and African American individuals were not low renin. The 469 diabetic subjects distributed across renin categories, as did the group as a whole.This systematic study of PRA in a large community sample of hypertensive patients reveals a wide distribution of activity level, with identifiable differences according to ethnicity, age, and sex but not diabetic status. However, these demographic differences were more quantitative than qualitative and do not provide a useful basis for estimation of the activity of the RAS. Instead, in hypertensive subjects, direct measurement of PRA is necessary, both for prognosis and for guiding hypertensive therapy.

Background The association of physical inactivity and elevated body mass index (BMI) with cardiovascular disease (CVD) risk is well established. The relationship of dietary caloric intake and CVD risk is less certain. Methods The epidemiologic follow-up of the First National Health and Nutrition Examination Survey (1971–1992) was examined to determine the relationship of caloric intake, BMI, and physical activity to CVD mortality. Of 14,407 participants, 9790 subjects aged 25 to 74 years met inclusion criteria. The CVD mortality rate was the outcome. Results During the 17 years of follow-up, there were 3183 deaths, 1531 of which were due to CVD (9.11/1000 person-years). People with relatively less physical activity, lower caloric intake, and who were overweight (BMI 25 to 29.9 kg/m2) and obese (BMI ≥30 kg/m2) had a less favorable baseline CVD risk profile than did those who were more active and of normal weight and had greater caloric intake. Age- and race/ethnicity–adjusted CVD mortality rates were highest among those with the least physical activity and lowest caloric intake, and who were overweight or obese. Moreover, subjects of normal weight who exercised most were more likely to have high caloric intake and lower CVD mortality (5.9 vs 14.7 per 1000 person-years, p =0.01) than subjects who were obese and exercised least. In Cox regression analysis, controlling for relevant CVD risk factors, least physical activity was independently associated with increased CVD mortality (hazard ratio=1.32, 95% confidence interval [CI]=1.13–1.53); and obesity was associated with increased CVD mortality (hazard ratio=1.24, 95% CI=1.06–1.44). Although highest dietary caloric intake was associated with reduced CVD mortality (hazard ratio=0.83, 95% CI=0.74–0.93), after adjusting for physical activity and BMI, there was no significant association of highest caloric intake with CVD mortality (hazard ratio=0.91, 95% CI=0.81–1.01). Conclusions In this large general population sample, lower levels of physical activity and obesity were independently associated with decreased CVD survival. Moreover, when BMI, physical activity, and other relevant characteristics were taken into account, caloric intake was not related to CVD mortality.