Association of parental obesity with concentrations of select systemic biomarkers in nonobese offspring: the Framingham Heart Study.

OBJECTIVE: Parental obesity is a risk factor for offspring obesity. It is unclear whether parental obesity also confers risk for obesity-associated conditions (e.g., a proinflammatory or prothrombotic state) in the absence of offspring obesity. RESEARCH DESIGN AND METHODS: We compared concentrations of multiple biomarkers representing distinct biological pathways (C-reactive protein [CRP], aldosterone, renin, B-type natriuretic peptide, NH(2)-terminal proatrial natriuretic peptide, fibrinogen, and plasminogen activator inhibitor-1) in nonobese Framingham Offspring Study participants with no parents (n = 665), one parent (n = 488), or two parents (n = 119) with obesity (BMI > or =30 kg/m(2)). RESULTS: Nonobese offspring with both parents with obesity had higher CRP levels (median 2.16 mg/l) than offspring with one parent (1.58 mg/l) or no parents (1.35 mg/l) with obesity. After multivariable adjustment, a nonlinear relationship with parental obesity became evident: compared with those without parental obesity, CRP levels were higher in offspring with two obese parents (P = 0.04) but not in offspring with only one obese parent (P = 0.76). Renin levels were more linearly related to parental obesity status, being significantly higher in offspring with one parent (P = 0.04) or two parents (P = 0.09) with obesity (P = 0.02 for trend). The other systemic biomarkers did not vary according to parental obesity status (all P > 0.05). CONCLUSIONS: Our findings suggest that offspring with a high risk of developing obesity have an altered biomarker profile, characterized by systemic inflammation and increased neurohormonal activity, even in the absence of obesity. This is consistent with the notion that parental obesity may confer an increased susceptibility to other adiposity-associated traits.

Interindividual variation in serum sodium and longitudinal blood pressure tracking in the Framingham Heart Study.

BACKGROUND: Recent cross-sectional studies have suggested that higher serum sodium levels may be a marker of elevated blood pressure. It is unclear whether serum sodium levels are related to the risk of developing hypertension in the community. METHODS: We investigated the association of serum sodium with longitudinal blood pressure tracking and incidence of hypertension in 2172 nonhypertensive Framingham Offspring Study participants (mean age 42 years, 54% women). We defined an increase in blood pressure as an increment of at least one category (as defined by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure), and incident hypertension as a systolic blood pressure of at least 140 or a diastolic blood pressure of at least 90 mmHg, or use of antihypertensive medications. Serum sodium was analyzed as a continuous variable, and as categories. RESULTS: Cross-sectionally, serum sodium was not associated with systolic or diastolic blood pressure (P exceeded 0.10). On follow-up (mean 4.4 years), 805 participants (37%, 418 women) progressed by at least one blood pressure category, and 318 (15%, 155 women) developed new-onset hypertension. In multivariable logistic regression analyses (adjusting for age, sex, baseline blood pressure, diabetes, BMI, weight gain and smoking), serum sodium was not associated with blood pressure progression (odds ratio per SD increment 0.93, 95% confidence interval 0.85-1.03), or with hypertension incidence (odds ratio per SD increment 0.94, 95% confidence interval 0.82-1.08). CONCLUSION: In our large community-based sample, serum sodium was not associated with blood pressure cross-sectionally, or with blood pressure tracking or hypertension incidence longitudinally.

Association of parental hypertension with concentrations of select biomarkers in nonhypertensive offspring.

Children of parents with hypertension are at increased risk of developing high blood pressure. We hypothesize that circulating concentrations of putative biomarkers (that may play a role in development of high blood pressure) are higher in nonhypertensive offspring of parents with hypertension. We compared concentrations of 4 different biomarkers (urinary albumin:creatinine ratio, circulating C-reactive protein, aldosterone:renin ratio, and plasminogen activator inhibitor-1) in nonhypertensive Framingham offspring study participants with none (n=233), 1 (n=474), or both (n=322) parents with hypertension. Parental hypertension was defined as onset before age 60 years, based on longitudinal observations of the original Framingham cohort. Serum C-reactive protein concentrations were higher in nonhypertensive offspring with 1 (median: 1.7; Q1 to Q3: 0.8 to 3.6 mg/L) or both parents with hypertension (median: 1.8; Q1 to Q3: 0.7 to 3.6 mg/L) compared with offspring without parental hypertension (median: 1.4; Q1 to Q3: 0.7 to 3.2 mg/L). In multivariable analyses, parental hypertension was associated with higher serum C-reactive protein concentration in offspring (15% increase per parent with hypertension; P=0.004). Prospectively, the relation of parental hypertension to longitudinal changes in blood pressure in the nonhypertensive offspring was attenuated on adjustment for C-reactive protein (P=0.04 for attenuation). The levels of the other biomarkers evaluated did not significantly differ in offspring according to parental hypertension status. In conclusion, serum C-reactive protein concentrations are higher in nonhypertensive offspring of parents with hypertension. These data suggest that inflammation may partly mediate the familial influences on hypertension risk.

BMI vs. waist circumference for identifying vascular risk.

OBJECTIVE: Current guidelines recommend measurement of both BMI and waist circumference (WC) in individuals with BMI between 25.0 and 34.9 kg/m(2). We investigated the relative contributions of BMI and WC toward identifying risk of adverse vascular events in a community-based sample. METHODS AND PROCEDURES: We evaluated Framingham Study participants (n = 4,195 person-examinations, 53% women) using pooled logistic regression to assess the incremental prognostic utility of WC in predicting risk of a first cardiovascular disease (CVD) event in the three BMI categories (normal, <25 kg/m(2); overweight, 25 to <30 kg/m(2); obese, > or =30 kg/m(2)) and to assess the incremental prognostic utility of BMI and WC separately for predicting risk of a first cardiovascular event. RESULTS: On follow-up (16 years), 430 participants (158 women) had experienced a first CVD event. In overweight women, but not in overweight men, larger WC was found to be an independent predictor of CVD incidence, longitudinally (in women, multivariable-adjusted odds ratio (OR) per s.d. increment in WC 1.86, 95% confidence interval (CI) = 1.03-3.36, P = 0.04; in men adjusted OR per s.d. increment in WC 0.91, 95% CI 0.60-1.38, P = 0.66). In obese individuals and in those with normal BMI, WC was not associated independently with incident CVD. When BMI and WC were analyzed separately for predicting risk of a first cardiovascular event, the c statistics associated with the multivariable CVD models incorporating BMI vs. WC were nearly identical in men and women. DISCUSSION: Knowledge of WC aids identification of vascular risk among overweight women. Among normal weight or obese women and men (regardless of BMI category) WC did not appear to substantially add to prediction of risk of vascular events.

A risk score for predicting near-term incidence of hypertension: the Framingham Heart Study.

BACKGROUND: Studies suggest that targeting high-risk, nonhypertensive individuals for treatment may delay hypertension onset, thereby possibly mitigating vascular complications. Risk stratification may facilitate cost-effective approaches to management. OBJECTIVE: To develop a simple risk score for predicting hypertension incidence by using measures readily obtained in the physician's office. DESIGN: Longitudinal cohort study. SETTING: Framingham Heart Study, Framingham, Massachusetts. PATIENTS: 1717 nonhypertensive white individuals 20 to 69 years of age (mean age, 42 years; 54% women), without diabetes and with both parents in the original cohort of the Framingham Heart Study, contributed 5814 person-examinations. MEASUREMENTS: Scores were developed for predicting the 1-, 2-, and 4-year risk for new-onset hypertension, and performance characteristics of the prediction algorithm were assessed by using calibration and discrimination measures. Parental hypertension was ascertained from examinations of the original cohort of the Framingham Heart Study. RESULTS: During follow-up (median time over all person-examinations, 3.8 years), 796 persons (52% women) developed new-onset hypertension. In multivariable analyses, age, sex, systolic and diastolic blood pressure, body mass index, parental hypertension, and cigarette smoking were significant predictors of hypertension. According to the risk score based on these factors, the 4-year risk for incident hypertension was classified as low (<5%) in 34% of participants, medium (5% to 10%) in 19%, and high (>10%) in 47%. The c-statistic for the prediction model was 0.788, and calibration was very good. LIMITATIONS: The risk score findings may not be generalizable to persons of nonwhite race or ethnicity or to persons with diabetes. The risk score algorithm has not been validated in an independent cohort and is based on single measurements of risk factors and blood pressure. CONCLUSION: The hypertension risk prediction score can be used to estimate an individual's absolute risk for hypertension on short-term follow-up, and it represents a simple, office-based tool that may facilitate management of high-risk individuals with prehypertension.

Vitamin D deficiency and risk of cardiovascular disease.

BACKGROUND: Vitamin D receptors have a broad tissue distribution that includes vascular smooth muscle, endothelium, and cardiomyocytes. A growing body of evidence suggests that vitamin D deficiency may adversely affect the cardiovascular system, but data from longitudinal studies are lacking. METHODS AND RESULTS: We studied 1739 Framingham Offspring Study participants (mean age 59 years; 55% women; all white) without prior cardiovascular disease. Vitamin D status was assessed by measuring 25-dihydroxyvitamin D (25-OH D) levels. Prespecified thresholds were used to characterize varying degrees of 25-OH D deficiency (< 15 ng/mL, < 10 ng/mL). Multivariable Cox regression models were adjusted for conventional risk factors. Overall, 28% of individuals had levels < 15 ng/mL, and 9% had levels < 10 ng/mL. During a mean follow-up of 5.4 years, 120 individuals developed a first cardiovascular event. Individuals with 25-OH D < 15 ng/mL had a multivariable-adjusted hazard ratio of 1.62 (95% confidence interval 1.11 to 2.36, P=0.01) for incident cardiovascular events compared with those with 25-OH D > or = 15 ng/mL. This effect was evident in participants with hypertension (hazard ratio 2.13, 95% confidence interval 1.30 to 3.48) but not in those without hypertension (hazard ratio 1.04, 95% confidence interval 0.55 to 1.96). There was a graded increase in cardiovascular risk across categories of 25-OH D, with multivariable-adjusted hazard ratios of 1.53 (95% confidence interval 1.00 to 2.36) for levels 10 to < 15 ng/mL and 1.80 (95% confidence interval 1.05 to 3.08) for levels < 10 ng/mL (P for linear trend=0.01). Further adjustment for C-reactive protein, physical activity, or vitamin use did not affect the findings. CONCLUSIONS: Vitamin D deficiency is associated with incident cardiovascular disease. Further clinical and experimental studies may be warranted to determine whether correction of vitamin D deficiency could contribute to the prevention of cardiovascular disease.

Synthesis and characterization of 5,10,15,20-tetra[3-(3-trifluoromethyl)phenoxy] porphyrin.

The newly synthesized 5,10,15,20-tetra[3-(3-trifluoromethyl)phenoxy]porphyrin, TTFMPP, has been characterized using mass spectroscopy, 1H-, 13C- and 19F-NMR, MALDI-TOF mass spectrometry, UV-Vis and fluorescence spectrophotometry, and cyclic voltammetry. The NMR confirmed the structure of the compound and the mass spectrum was in agreement with the proposed molecular formula. The UV-Vis absorption spectrum of TTFMPP shows characteristic spectral patterns similar to those of tetraphenyl porphryin, with a Soret band at 419 nm and four Q bands at 515, 550, 590, and 648 nm. Protonation of the porphyrin with TFA resulted in the expected red shift of the Soret band. Excitation at 419 nm gave an emission at 650 nm. The quantum yield of the porphyrin was determined to be 0.08. Cyclic voltammetry was used to determine the oxidation and reduction potentials of the new porphyrin. Two quasi-reversible one-electron reductions at -1.00 and -1.32 V and a quasi-reversible oxidation at 1.20 V versus the silver/silver chloride reference electrode with tetrabutylammonium tetrafluoroborate as the supporting electrolyte in methylene chloride were observed.

Multimarker approach to evaluate the incidence of the metabolic syndrome and longitudinal changes in metabolic risk factors: the Framingham Offspring Study.

BACKGROUND: The metabolic syndrome (MetS) is associated with increased cardiovascular risk. We evaluated the relative contributions of circulating biomarkers representing distinct biological pathways to the incidence of MetS and to longitudinal changes of its constituent risk factors. METHODS AND RESULTS: We measured 8 circulating biomarkers reflecting inflammation (C-reactive protein), hemostasis (plasminogen activator inhibitor-1, fibrinogen), neurohormonal activity (aldosterone, renin, B-type natriuretic peptide, N-terminal proatrial natriuretic peptide), and endothelial dysfunction (homocysteine) in 2292 Framingham Offspring Study participants (mean age, 57 years; 56% women). We related the biomarker panel to incidence of MetS on follow-up initially and then related biomarkers associated with incident MetS to longitudinal change in its components. On follow-up (mean, 2.9 years), 282 participants (of 1473 participants without prevalent MetS at baseline) developed MetS. After adjustment for clinical risk factors, the biomarker panel was associated with incident MetS (P=0.008). On backward elimination, plasminogen activator inhibitor-1 and aldosterone remained associated with incident MetS (multivariable-adjusted odds ratio per 1-SD increment log marker, 1.31 [P=0.004] and 1.21 [P=0.015], respectively). In multivariable analyses evaluating longitudinal change in MetS components (analyzed as continuous variables), plasminogen activator inhibitor-1 was significantly and positively associated with changes in fasting glucose, systolic blood pressure, and triglycerides (all P<0.05). Serum aldosterone was associated positively with change in systolic blood pressure (P=0.023) and inversely with change in high-density lipoprotein cholesterol (P=0.001). CONCLUSIONS: Higher circulating plasminogen activator inhibitor-1 and aldosterone levels are associated with the development of MetS and with longitudinal change of its components, suggesting that these biomarkers and related pathways play a key role in mediating metabolic risk.

Increasing trends in incidence of overweight and obesity over 5 decades.

PURPOSE: We evaluated trends in the incidence of overweight and obesity over the past 50 years. METHODS: We evaluated trends in the incidence of overweight (25< or =body mass index [BMI] <30 kg/m2), obesity (BMI > or =30 kg/m2) and stage 2 obesity (BMI > or =35 kg/m2) from 1950 to 2000 in Framingham Study participants (n=6798, 54% women). Individuals aged 40-55 years who attended 2 examinations 8 years apart in each decade were eligible. RESULTS: The incidences of overweight, obesity, and stage 2 obesity increased across the decades in both sexes (P for trend <.001). For men, the incidence of overweight rose from 21.8% (95% confidence interval [CI], 17.6-26.5) in the 1950s to 35.2% (95% CI, 28.6-42.5) in the 1990s; of obesity from 5.8% (95% CI, 4.4-7.6) to 14.8% (95% CI, 12.2-17.9); and of stage 2 obesity from 0.2% (95% CI, 0.1-0.9) to 5.4% (95% CI, 4.0-7.2). For women, incidence rates of overweight increased from 15.0% (95% CI, 12.3-18.1) to 33.1% (95% CI, 29.0-37.4); of obesity from 3.9% (95% CI, 2.9-5.3) to 14% (95% CI, 11.6-16.7); and of stage 2 obesity from 1.7% (95% CI, 1.1-2.6) to 4.4% (95% CI, 3.2-6.0). Overall, incidence rates of overweight increased 2-fold and that of obesity more than 3-fold over 5 decades, findings that remained robust upon additional adjustment for baseline BMI in each decade. CONCLUSIONS: The incidence of overweight and obesity increased progressively over the last 5 decades, suggesting that the rising trend in prevalence is not a recent phenomenon.