Salt and cardiovascular disease: insufficient evidence to recommend low sodium intake.

Several blood pressure guidelines recommend low sodium intake (<2.3 g/day, 100 mmol, 5.8 g/day of salt) for the entire population, on the premise that reductions in sodium intake, irrespective of the levels, will lower blood pressure, and, in turn, reduce cardiovascular disease occurrence. These guidelines have been developed without effective interventions to achieve sustained low sodium intake in free-living individuals, without a feasible method to estimate sodium intake reliably in individuals, and without high-quality evidence that low sodium intake reduces cardiovascular events (compared with moderate intake). In this review, we examine whether the recommendation for low sodium intake, reached by current guideline panels, is supported by robust evidence. Our review provides a counterpoint to the current recommendation for low sodium intake and suggests that a specific low sodium intake target (e.g. <2.3 g/day) for individuals may be unfeasible, of uncertain effect on other dietary factors and of unproven effectiveness in reducing cardiovascular disease. We contend that current evidence, despite methodological limitations, suggests that most of the world's population consume a moderate range of dietary sodium (2.3-4.6g/day; 1-2 teaspoons of salt) that is not associated with increased cardiovascular risk, and that the risk of cardiovascular disease increases when sodium intakes exceed 5 g/day. While current evidence has limitations, and there are differences of opinion in interpretation of existing evidence, it is reasonable, based upon observational studies, to suggest a population-level mean target of <5 g/day in populations with mean sodium intake of >5 g/day, while awaiting the results of large randomized controlled trials of sodium reduction on incidence of cardiovascular events and mortality.

Water and sodium in heart failure: a spotlight on congestion.

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.

How much effect of different antihypertensive medications on cardiovascular outcomes is attributable to their effects on blood pressure?

The debate over whether certain antihypertensive medications have benefits beyond what would be expected from their blood pressure lowering spurred the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, which randomized 42,418 participants to chlorthalidone (15,255), amlodipine (9048), lisinopril (9054), or doxazosin (9061). We compared chlorthalidone, the active control, with each of the other three agents with respect to the primary outcome, fatal coronary heart disease or nonfatal myocardial infarction, and several other clinical endpoints. The arms were similar with respect to the primary endpoint, although some differences were found for other endpoints, most notably heart failure. Although the desire was to achieve similar blood pressure reductions in the four arms, we found some systolic blood pressure and diastolic blood pressure differences. A natural question is to what degree can observed treatment group differences in cardiovascular outcomes be attributed to these blood pressure differences. The purpose of this paper was to delineate the problems inherent in attempting to answer this question, and to present analyses intended to overcome these problems.

Dietary sodium intake and cardiovascular mortality: controversy resolved?

Universal reduction in sodium intake has long been recommended, largely because of its proven ability to lower blood pressure for some. However, multiple randomized trials have also demonstrated that similar reductions in sodium increase plasma renin activity and aldosterone secretion, insulin resistance, sympathetic nerve activity, serum cholesterol and triglyceride levels. Thus, the health consequences of reducing sodium cannot be predicted by its impact on any single physiologic characteristic but will reflect the net of conflicting effects. Some 23 observational studies (>360,000 subjects and >26,000 end points) linking sodium intake to cardiovascular outcomes have yielded conflicting results. In subjects with average sodium intakes of less than 4.5 grams/day, most have found an inverse association of intake with outcome; in subjects with average intakes greater than 4.5 grams/day, most reported direct associations. Finally, in two, a "J-shaped" relation was detected. In addition, three randomized trials have found that heart failure subjects allocated to 1.8 g of sodium have significantly increased morbidity and mortality compared with those at 2.8 g. At the same time, a randomized study in retired Taiwanese men found that allocation to an average intake of 3.8 g improved survival compared with 5.3 g. Taken together, these data provide strong support for a "J-shaped" relation of sodium to cardiovascular outcomes. Sodium intakes above and below the range of 2.5 to 6.0 grams/day are associated with increased cardiovascular risk. This robust body of evidence does not support universal reduction of sodium intake.

The effects of vitamin D repletion on endothelial function and inflammation in patients with coronary artery disease.

Adequate vitamin D levels may promote cardiovascular health by improving endothelial function and down-regulating inflammation. The objective of this pilot trial was to investigate the effects of vitamin D repletion on endothelial function and inflammation in patients with coronary artery disease (CAD). Using a double-blind placebo wait-list control design, 90 subjects with CAD and vitamin D deficiency (< 20 ng/ml) were randomized 1:1 to 50,000 IU of oral ergocalciferol or placebo weekly for 12 weeks. Endothelial function (reactive hyperemia peripheral arterial tonometry, RH-PAT), circulating adhesion molecules, and pro-inflammatory cytokines were measured at baseline and 12 weeks. The median increase in serum 25-vitamin D from baseline was 26 ± 17 ng/ml in the active group and 4 ± 8 ng/ml in the placebo group (between-group difference = 22 ng/ml, p < 0.001). The median within-subject change in RH-PAT score was 0.13 ± 0.73 with active treatment and -0.04 ± 0.63 with placebo (between-group difference = 0.17, p = 0.44). Within-group and between-group differences in intercellular adhesion molecule levels were greater with placebo (between-group difference = 6 ng/ml, p = 0.048). Vascular cell adhesion molecule levels decreased in both groups by a similar magnitude (median difference between groups = 8.5 ng/ml, p = 0.79). There was no difference between groups in magnitude of reduction in interleukin (IL)-12 (-8.6 ng/ml, p = 0.72) and interferon-gamma (0.52 ng/ml, p = 0.88). No significant differences in blood pressure, e-selectin, high-sensitivity c-reactive protein, IL-6 or the chemokine CXCL-10 were found with treatment. In conclusion, repleting vitamin D levels in subjects with CAD failed to demonstrate any benefits on surrogate markers of cardiovascular health. These results question the role of vitamin D supplementation in modifying cardiovascular disease.

Low Diastolic Blood Pressure and Mortality in Older Women. Results From the Women's Health Initiative Long Life Study.

BACKGROUND: Recommended systolic blood pressure targets often do not consider the relationship of low diastolic blood pressure (DBP) levels with cardiovascular disease (CVD) and all-cause mortality risk, which is especially relevant for older people with concurrent comorbidities. We examined the relationship of DBP levels to CVD and all-cause mortality in older women in the Women's Health Initiative Long Life Study (WHI-LLS). METHODS: The study sample included 7,875 women (mean age: 79 years) who underwent a blood pressure measurement at an in-person home visit conducted in 2012-2013. CVD and all-cause mortality were centrally adjudicated. Hazard ratios (HRs) were obtained from adjusted Cox proportional hazards models. RESULTS: After 5 years follow-up, all-cause mortality occurred in 18.4% of women. Compared with a DBP of 80 mm Hg, the fully adjusted HR for mortality was 1.33 (95% confidence interval [CI]: 1.04-1.71) for a DBP of 50 mm Hg and 1.67 (95% CI: 1.29-2.16) for a DBP of 100 mm Hg. The HRs for CVD were 1.14 (95% CI: 0.78-1.67) for a DBP of 50 mm Hg and HR 1.50 (95% CI: 1.03-2.17) for a DBP of 100 mm Hg. The nadir DBP associated with lowest mortality risk was 72 mm Hg overall. CONCLUSIONS: In older women, consideration should be given to the potential adverse effects of low and high DBP. Low DBP may serve as a risk marker. DBP target levels between 68 and 75 mm Hg may avoid higher mortality risk.

Hypertension: evolving from standardized to individualized care.

: The hypertension paradigm has contributed to a dramatic reduction in CVD mortality. This has been achieved by applying average results of population studies to identify a target population and design a common intervention to achieve a BP goal. Progressive lowering of the BP threshold has expanded the fraction of persons at risk who have access to treatment. Meanwhile, falling risk reduces potential benefit, while treatment-induced adverse events increase - making further expansion of the treatment pool no longer tenable. Still, CVD remains the leading cause of death. Fortunately, new science reveals opportunities to enhance CVD prevention when BP management is based upon individual characteristics. Treatment can be directed at those most likely to benefit, while sparing others the hazards of unnecessary therapy. Treatment can be designed to achieve a variety of physiological objectives that influence cardiovascular outcomes. This new strategy should improve both the efficacy and efficiency of BP-related CVD prevention.

Sodium intake and mortality follow-up in the Third National Health and Nutrition Examination Survey (NHANES III).

BACKGROUND: Sodium restriction is commonly recommended as a measure to lower blood pressure and thus reduce cardiovascular disease (CVD) and all-cause mortality. However, some studies have observed higher mortality associated with lower sodium intake. OBJECTIVE: To test the hypothesis that lower sodium is associated with subsequent higher cardiovascular disease (CVD) and all cause mortality in the Third National Health and Nutrition Examination Survey (NHANES III). DESIGN: Observational cohort study of mortality subsequent to a baseline survey. PARTICIPANTS: Representative sample (n = 8,699) of non-institutionalized US adults age > or = 30, without history of CVD events, recruited between 1988-1994. MEASUREMENTS AND MAIN RESULTS: Dietary sodium and calorie intakes estimated from a single baseline 24-h dietary recall. Vital status and cause of death were obtained from the National Death Index through the year 2000. Hazard ratio (HR) for CVD mortality of lowest to highest quartile of sodium, adjusted for calories and other CVD risk factors, in a Cox model, was 1.80 (95% CI 1.05, 3.08, p = 0.03). Non-significant trends of an inverse association of continuous sodium (per 1,000 mg) intake with CVD and all-cause mortality were observed with a 99% CI of 0.73, 1.06 (p = 0.07) and 0.86, 1.04 (p = 0.11), respectively, while trends for a direct association were not observed. CONCLUSION: Observed associations of lower sodium with higher mortality were modest and mostly not statistically significant. However, these findings also suggest that for the general US adult population, higher sodium is unlikely to be independently associated with higher CVD or all-cause mortality.

New onset diabetes during antihypertensive therapy.

New onset diabetes (NOD) is common among hypertensive patients, whether they are being treated for hypertension or not, and is associated with subsequently increased cardiovascular disease (CVD). Thiazide-like diuretics and beta-blockers are more likely to provoke hyperglycemia when compared with drugs that block the renin-angiotensin system, and calcium channel blockers. However, in contrast to the NOD arising during treatment with other antihypertensive drugs, the NOD that occurs during diuretic treatment, has not been shown to increase CVD, either in clinical trials, or during longer observational studies. In fact, blood pressure reduction achieved by diuretic treatment may avert the expected increase of CVD in NOD. Conventional blood pressure reduction (along with lipid lowering) is the proven approach to preventing CVD in diabetes, in whatever circumstances the diabetes occurs. Apprehensions relating to the potential onset of NOD should not influence the choice of the initial antihypertensive treatment choice, nor should it invariably lead to discontinuation of diuretics (although such a step may reverse hyperglycemia). NOD can also sometimes be eliminated by correcting hypokalemia with a potassium-sparing diuretic, and/or potassium supplementation, or by adding a potassium-conserving antihypertensive drug such as an ACEI, ARB, or an anti-aldosterone agent. If all these stratagems fail (or are unsuitable), and the diuretic is essential to blood pressure control, then hypoglycemic therapy is indicated. NOD does adversely affect quality of life, and is not to be accepted lightly. However, diuretic-induced hyperglycemia can be managed, and should be tolerated if a diuretic is essential for blood pressure control. In summary, the potential for occurrence of NOD certainly needs consideration, but it is not an insurmountable challenge, and must not compromise aggressive blood pressure control, which remains the primary tool for antihypertensive care.

Hypertension control at physicians' offices in the United States.

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 <130/80 mm Hg, 140/90 mm Hg, and 145/95 mm Hg, respectively. The likelihood of hypertension control (<140/90 mm Hg) was associated with a diagnosis of coronary heart disease (odds ratio (OR) 1.54, 95% confidence interval (CI) = 1.01-2.35), visits with increased serum cholesterol (OR = 1.34, 95% CI = 1.09-1.65), visits with patients' primary care physician vs. those with non-primary care physicians (OR = 1.49, 95% CI = 1.05-2.10), and visits with internists (OR = 1.32, 95% CI = 1.05-1.67) or cardiologists (OR = 1.70, 95% CI = 1.17-2.471) vs. those with family physicians. Age, gender, race/ethnicity, health insurance status, and prescription of types of antihypertensive medicine were not associated with hypertension control in office visits. CONCLUSIONS: The hypertension control rate of 44% in US office visits leaves substantial room for improvement. A strong emphasis on improving hypertension management is needed to reduce hypertension-related morbidity and mortality.

Vascular disease among hospitalized multiple sclerosis patients.

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 study included 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.