The mechanisms underlying high blood pressure in the framework of metabolic syndrome (MS) are not clarified: we thus analyzed the relationship of MS and its components to renal tubular sodium ...handling among participants of the Olivetti Heart Study, an epidemiological investigation of a representative sample of adult white male population in southern Italy.
Proximal (FPRNa) and distal (FDRNa) fractional sodium reabsorption were estimated by the clearance of exogenous lithium in 702 participants aged 25-75 years examined in 1994-1995. Blood pressure and relevant anthropometric and biochemical variables were also measured. The diagnosis of MS was based on modified National Cholesterol Education Program (NCEP)-Adult Treatment Panel III (ATP III) criteria.
FPRNa, but not FDRNa, was directly associated with body mass index (BMI), waist circumference, diastolic pressure, serum triglyceride and uric acid, independently of age and of antihypertensive treatment. After adjustment for age, FPRNa, but not FDRNa, was significantly greater in individuals with MS, as compared to those without 77.6% (95% confidence interval = 76.7-80.1) versus 74.4% (73.7-75.1), P < 0.001. A similar difference was observed after the exclusion of participants on current antihypertensive treatment (P = 0.018). In untreated individuals, a significant interaction was observed between obesity and insulin resistance as related to FPRNa (P = 0.002): the highest age-adjusted levels of FPRNa were detected in obese hypertensive and obese insulin-resistant participants.
In this sample of an adult male population, MS was associated with an increased rate of FPRNa. This finding is relevant to the pathophysiology of MS and possibly to the prevention of its cardiovascular and renal consequences.
Sodium plays an important pathophysiological role in blood pressure (BP) values and in the development of hypertension, and epidemiological studies such as the Intersalt Study have shown that the ...increase in BP occurring with age is determined by salt intake. Recently, a meta-analysis of 13 prospective studies has also shown the close relationship between excess sodium intake and higher risk of stroke and total cardiovascular events. However, the BP response to changing salt intake displayed a marked variability, as first suggested by Kawasaki et al. (The effect of high-sodium and low-sodium intakes on blood pressure and other related variables in human subjects with idiopathic hypertension. Am J Med 1978; 64: 193-198) and later by Weinberger et al. (Definitions and characteristics of sodium sensitivity and blood pressure resistance. Hypertension 1986; 8: II127-II134), who recognized the heterogeneity of the BP response to salt and developed the concept of salt sensitivity. We have a large body of evidence in favour of a major role of metabolic and neuro-hormonal factors in determining BP salt sensitivity in association with the effect of genetic variation. There is evidence that salt sensitivity influences the development of organ damage, even independently-at least in part-of BP levels and the occurrence of hypertension. In addition, several observational studies indicate that salt sensitivity is clearly associated with a higher rate of cardiovascular events and mortality, independently of BP levels and hypertension. A cluster of factors with well-known atherogenic potential such as hyperinsulinaemia, dyslipidaemia and microalbuminuria-all known to be prevalent in salt-sensitive hypertension-might at least partially explain the increased cardiovascular risk observed in salt sensitive individuals. The gold standard for the evaluation of BP salt sensitivity is the BP response to a moderate reduction of salt intake for several weeks; nevertheless, these protocols often suffer of poor patient compliance to dietary instructions. To overcome this problem, short-term tests have been proposed that evaluate either large differences in salt intake for a few days or the response to intravenous administration of saline solution and short-acting diuretics. Recently, the use of ambulatory BP measurement has been proposed for the clinical assessment of BP salt sensitivity. Noteworthy, BP salt sensitivity, in whomever or however assessed, behaves as a continuous variable but salt sensitivity is used as a categorical parameter, with salt-sensitive individuals being defined as those with a difference in BP between low- and high-sodium intake >10%, and salt-resistant subjects those in whom BP does not increase or shows an increase <5% under sodium loading. The general conclusion that can and should be drawn from the above considerations is that the paradigm of salt sensitivity, despite its important pathophysiological meaning, is not helpful, so far, to the practising physician in clinical practice nor is it relevant or useful to the design and implementation of a population-based strategy of salt intake reduction; however, further studies are warranted for an accurate assessment of the salt-sensitivity phenotype in clinical practice. In the absence of a population strategy for salt intake reduction, the aim should be the generation of a 'low sodium environment' allowing for a dietary salt intake tailored on true human requirements and not on deleterious lifestyle habits.
Abstract Background Circulating endotoxin levels are associated with atherosclerosis. Moreover, ethnic differences in pro-inflammatory markers may be associated with ethnic differences in ...atherosclerotic and cardiovascular (CVD) and coronary heart disease (CHD) risk. Objective and methods To investigate ethnic differences in circulating plasma endotoxin levels, its soluble receptor (sCD14), and high-sensitivity CRP (hs-CRP). 192 individuals, aged 40–59 years (61 white (30 women), 68 of African origin (33 women) and 63 South Asians (33 women)), free from coronary heart disease (CHD), stroke, CVD and diabetes were randomly selected from the UK ‘Wandsworth Heart and Stroke Study’. Results Age-adjusted endotoxin levels were lower in women than in men ( p = 0.002) and were highest in South Asians (13.3 EU/mL 95% CI 12.0–14.7) and lowest in individuals of African origin (10.1 EU/mL 9.1–11.1) than in whites ( p for linear trend <0.001). Endotoxin levels were positively associated with waist, waist–hip ratio, total cholesterol, serum triglycerides and serum insulin levels and negatively associated with serum HDL-cholesterol. Serum hs-CRP and plasma sCD14 varied by ethnic group ( p < 0.001) but was not associated with endotoxin. Conclusions This study is the first to indicate a graded increase in endotoxin levels from black Africans to whites to South Asians, which is consistent with the ethnic difference in CHD risk. Whilst these findings support the concept that the innate immune system (IIS) may contribute significantly to the metabolic component underlying the development of CVD and CHD risk, further studies are required to see whether endotoxin levels are causally related to the development of CHD.
The renin-angiotensin system is involved in adipocyte growth and differentiation and possibly in adipose tissue metabolism.
To investigate the association of polymorphism in the ...angiotensin-converting enzyme (ACE) I/D gene, angiotensinogen M235T gene, and angiotensin II type 1 receptor A1166C gene with body mass index, body fat pattern, and obesity-associated hypertension.
Cross-sectional longitudinal study.
The Olivetti factories in Marcianise and Pozzuoli, suburbs of Naples, Italy.
959 adult men, 25 to 75 years of age.
Renin-angiotensin system polymorphism, anthropometric indexes, blood pressure, and serum glucose and insulin levels.
No association was detected between angiotensinogen or angiotensin II type 1 receptor gene polymorphism and anthropometric indexes or blood pressure. For ACE I/D polymorphism, significant age-genotype interaction was detected on cross-sectional observation; the relation of body mass index, waist circumference, and diastolic blood pressure to age was significantly greater in persons with the DD genotype than in those with the ID or II genotype. Overweight and abdominal adiposity were more common in men with the DD genotype, particularly among older participants (51.1% vs. 36.5% and 33.1% vs. 22.0%, respectively). Odds ratios were 1.82 (95% CI, 1.16 to 2.87) for overweight and 1.76 (CI, 1.06 to 2.90) for abdominal adiposity. Among 314 untreated men first examined 20 years earlier, those with the DD genotype had greater age-adjusted weight gain (1.45 kg CI, 0.12 to 2.78 kg) and change in diastolic blood pressure (2.83 mm Hg CI, 0.39 to 5.28 mm Hg). The relative risk for overweight was 2.34 (CI, 1.32 to 4.15) among participants with the DD genotype versus those with the ID or II genotype.
The ACE I/D polymorphism was a significant predictor of overweight and abdominal adiposity in men. DD homozygosity was associated with larger increases in body weight and blood pressure in aging persons, as well as with higher incidence of overweight.
OBJECTIVE: To assess the relationship between habitual sleep disturbances and the incidence of type 2 diabetes and to obtain an estimate of the risk. RESEARCH DESIGN AND METHODS: We conducted a ...systematic search of publications using MEDLINE (1955-April 2009), EMBASE, and the Cochrane Library and manual searches without language restrictions. We included studies if they were prospective with follow-up >3 years and had an assessment of sleep disturbances at baseline and incidence of type 2 diabetes. We recorded several characteristics for each study. We extracted quantity and quality of sleep, how they were assessed, and incident cases defined with different validated methods. We extracted relative risks (RRs) and 95% CI and pooled them using random-effects models. We performed sensitivity analysis and assessed heterogeneity and publication bias. RESULTS: We included 10 studies (13 independent cohort samples; 107,756 male and female participants, follow-up range 4.2-32 years, and 3,586 incident cases of type 2 diabetes). In pooled analyses, quantity and quality of sleep predicted the risk of development of type 2 diabetes. For short duration of sleep (less-than or equal to5-6 h/night), the RR was 1.28 (95% CI 1.03-1.60, P = 0.024, heterogeneity P = 0.015); for long duration of sleep (>8-9 h/night), the RR was 1.48 (1.13-1.96, P = 0.005); for difficulty in initiating sleep, the RR was 1.57 (1.25-1.97, P < 0.0001); and for difficulty in maintaining sleep, the RR was 1.84 (1.39-2.43, P < 0.0001). CONCLUSIONS: Quantity and quality of sleep consistently and significantly predict the risk of the development of type 2 diabetes. The mechanisms underlying this relation may differ between short and long sleepers.
Objective To assess the relation between the level of habitual salt intake and stroke or total cardiovascular disease outcome.Design Systematic review and meta-analysis of prospective studies ...published 1966-2008.Data sources Medline (1966-2008), Embase (from 1988), AMED (from 1985), CINAHL (from 1982), Psychinfo (from 1985), and the Cochrane Library. Review methods For each study, relative risks and 95% confidence intervals were extracted and pooled with a random effect model, weighting for the inverse of the variance. Heterogeneity, publication bias, subgroup, and meta-regression analyses were performed. Criteria for inclusion were prospective adult population study, assessment of salt intake as baseline exposure, assessment of either stroke or total cardiovascular disease as outcome, follow-up of at least three years, indication of number of participants exposed and number of events across different salt intake categories.Results There were 19 independent cohort samples from 13 studies, with 177 025 participants (follow-up 3.5-19 years) and over 11 000 vascular events. Higher salt intake was associated with greater risk of stroke (pooled relative risk 1.23, 95% confidence interval 1.06 to 1.43; P=0.007) and cardiovascular disease (1.14, 0.99 to 1.32; P=0.07), with no significant evidence of publication bias. For cardiovascular disease, sensitivity analysis showed that the exclusion of a single study led to a pooled estimate of 1.17 (1.02 to 1.34; P=0.02). The associations observed were greater the larger the difference in sodium intake and the longer the follow-up.Conclusions High salt intake is associated with significantly increased risk of stroke and total cardiovascular disease. Because of imprecision in measurement of salt intake, these effect sizes are likely to be underestimated. These results support the role of a substantial population reduction in salt intake for the prevention of cardiovascular disease.
Arterial stiffness is an independent cardiovascular risk factor and sodium intake could be a determinant of arterial stiffness. Nevertheless, the studies that investigated the effect of reducing ...dietary sodium intake on arterial stiffness in humans provided inconsistent results. Therefore, we performed a systematic review and a meta-analysis of the available randomized controlled trials of salt restriction and arterial stiffness to try and achieve more definitive conclusions.
A systematic search of the online databases available (from 1996 through July 2017) was conducted including randomized controlled trials that reported arterial stiffness, expressed by carotid-femoral pulse wave velocity (PWV), as difference between the effects of two different sodium intake regimens. For each study, the mean difference and 95% confidence intervals were pooled using a random effect model. Sensitivity, heterogeneity, publication bias, subgroup and meta-regression analyses were performed.
Eleven studies met the predefined inclusion criteria and provided 14 cohorts with 431 participants and 1-6 weeks intervention time. In the pooled analysis, an average reduction in sodium intake of 89.3 mmol/day was associated with a 2.84% (95% CI: 0.51-5.08) reduction in PWV. There was no significant heterogeneity among studies and no evidence of publication bias was detected. No single feature of the studies analyzed seemed to impact on the effect of salt restriction on PWV.
The results of this meta-analysis indicate that restriction of dietary sodium intake reduces arterial stiffness. This effect seems be at least in part independent of the changes in blood pressure.
Excess dietary salt intake represents a predominant cause of hypertension. However, individual blood pressure response to salt is heterogeneous, possibly due to different inherited susceptibility. ...The early identification of rare monogenic forms of hypertension associated with abnormalities of renal tubular sodium handling and response to diuretics highlighted the important role of renal alterations in salt-sensitive hypertension. Thereafter, interest has concentrated on the identification of more common allelic variants of candidate genes for hypertension in relation to the salt-sensitivity phenotype. By now, relatively large numbers of such variants have been described, and the pathogenic role of gene-gene interaction has received increasing attention. The alternative approach, consisting of the search for quantitative trait loci in the human genome linked to the transmission of salt-sensitive hypertension, has so far been less successful and cost-effective. This review summarizes consolidated knowledge and discusses the most recent novel findings on the impact of genetic variance on salt-sensitivity of blood pressure.
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