Relative Contributions of Pulse Pressure and Arterial Stiffness to Cardiovascular Disease The Framingham Heart Study

Pulse pressure has been frequently used as a surrogate marker of arterial compliance. However, the prevalence and prognostic significance of mismatch between pulse pressure and arterial stiffness remains unclear. We measured carotid-femoral pulse wave velocity (CFPWV) and central pulse pressure (CPP) in 2119 Framingham Offspring Cohort participants (mean age, 60 years; 57% women). The participants were divided into 4 groups according to CPP and CFPWV status (categorized as high/low based on >= age- and sex-specific median values) and followed up for cardiovascular disease (CVD) events. At baseline, 832 of 2119 (39%) participants had discordant CPP and CFPWV status, 417 with low CPP and high CFPWV, and 415 with high CPP and low CFPWV. The multivariable-adjusted risk for CVD events (n= 246; median follow-up, 12.6 years) in individuals with a CPP-CFPWV mismatch (hazard ratio for low CPP with high CFPWV, 1.21; 95% CI, 0.83-1.76; hazard ratio for high CPP with low CFPWV, 0.76; 95% CI, 0.49-1.19) was comparable with the CVD risk observed in the low CPP with low CFPWV (referent group). In contrast, participants with a high CPP with high CFPWV (hazard ratio, 1.52; 95% CI, 1.10-2.11) experienced significantly increased CVD risk. The interaction term between CPP and CFPWV status on CVD risk was borderline significant in the multivariable model (P=0.08). Our results demonstrate that pulse pressure-arterial stiffness mismatch is common in the community. CFPWV may modify the association of CPP with CVD risk, with the greatest risk being observed in those with elevated CPP and CFPWV

Association between thyroid-stimulating hormone and blood pressure in adults: an 11-year longitudinal study

BACKGROUND: The results of longitudinal studies on the association between thyroid function and blood pressure (BP) are divided. This study aimed to investigate this association in cross-sectional and longitudinal settings in a nationwide, random sample representative of the Finnish adult population aged 30 and over. METHODS: The study sample was randomly drawn from the population register. A total of 5655 participants were included in the baseline analyses and 3453 in the 11-year prospective analyses. The associations between baseline TSH and (i) BP and BP change over time; and (ii) prevalent and incident hypertension were assessed using linear and logistic models, adjusted for age, gender, smoking and body mass index. RESULTS: A positive association (β ± standard error) was observed between TSH and diastolic (0·36 ± 0·12, P = 0·003) but not systolic BP (0·16 ± 0·21, P = 0·45) at baseline. TSH was negatively associated with 11-year BP change in men (systolic: -0·92 ± 0·41, P = 0·03; diastolic: -0·66 ± 0·26, P = 0·01) but not in women (P ≥ 0·09 for systolic and diastolic BP change). Participants in the highest TSH tertile within the TSH reference interval (0·4-3·4 mU/L), as compared with the lowest, had increased odds of prevalent (odds ratio 1·22, 95% confidence interval 1·05-1·43, P = 0·01) but not incident hypertension (odds ratio 0·93, 95% confidence interval 0·73-1·19, P = 0·58). CONCLUSIONS: A modest association was found between increasing TSH and prevalent but not incident hypertension. TSH was inversely associated with BP change in men in our study. These findings contest an independent role of thyroid function at normal to near-normal levels in the pathogenesis of hypertension.</p

Association of thyroid-stimulating hormone with lipid concentrations: an 11-year longitudinal study

BACKGROUND:Scant data exist on the longitudinal association between thyroid function and lipid concentrations. We investigated associations of TSH and lipid concentrations cross-sectionally and longitudinally in a nationwide population sample.METHODS:A total of 5205 randomly sampled participants representative of Finns aged ≥30 years were examined in 2000-2001 and included in cross-sectional analyses. A total of 2486 were re-examined 11 years later and included in longitudinal analyses. With linear regression models adjusted for age, gender, smoking and body mass index, we assessed the associations of baseline TSH and TSH categories (low, reference range and high) with total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol; apolipoprotein A1 and B; and triglycerides at baseline and follow-up.RESULTS:At baseline, higher TSH associated with higher total cholesterol (β = 0·025, standard error [SE] = 0·007, P < 0·001), LDL cholesterol (β = 0·020, SE = 0·007, P = 0·002), apolipoprotein B (β = 0·006, SE = 0·002, P < 0·001) and log triglycerides (β = 0·008, SE = 0·003, P = 0·004), but not with other lipid outcomes. Higher baseline TSH associated with higher total cholesterol (β = 0·056, SE = 0·026, P = 0·033), LDL cholesterol (β = 0·057, SE = 0·023, P = 0·015) and apolipoprotein B (β = 0·012, SE = 0·006, P = 0·028) at follow-up in women, but not with any lipid outcomes in men. Participants with high TSH at baseline had a 0·22 mmol/l (95% confidence interval 0·02-0·41 mmol/l) higher LDL cholesterol at follow-up (P = 0·028) than participants with TSH in the reference range (0·4-3·4 mU/l). However, exclusion of participants with high-risk baseline lipid values rendered these positive longitudinal associations nonsignificant (P ≥ 0·098).CONCLUSIONS:We could confirm a modest association between higher TSH and an adverse lipid profile cross-sectionally but not indisputably longitudinally.</p

Thyroid-stimulating hormone reference range and factors affecting it in a nationwide random sample

Objectives: Previous studies with mainly selected populations have proposed contradicting reference ranges for TSH and have disagreed on how screening, age and gender affect them. This study aimed to determine a TSH reference range on the Abbott Architect ci8200 integrated system in a large, nationwide, stratified random sample. To our knowledge this is the only study apart from the NHANES III that has addressed this issue in a similar nationwide setting. The effects of age, gender, TPOAb-positivity and medications on TSH reference range were also assessed. &nbsp; Methods: TSH was measured from 6247 participants randomly drawn from the population register to represent the Finnish adult population. TSH reference ranges were established of a thyroid-healthy population and its subpopulations with increasing and cumulative rigour of screening: screening for overt thyroid disease (thyroid-healthy population, n=5709); screening for TPOAb-positivity (risk factor-free subpopulation, n=4586); and screening for use of any medications (reference subpopulation, n=1849). &nbsp; Results: The TSH reference ranges of the thyroid-healthy population, and the risk factor-free and reference subpopulations were 0.4 &ndash; 4.4, 0.4 &ndash; 3.7 and 0.4 &ndash; 3.4 mU/L (2.5th &ndash; 97.5th percentiles), respectively. Although the differences in TSH between subgroups for age (P=0.002) and gender (P=0.005) reached statistical significance, the TSH distribution curves of the subgroups were practically superimposed. &nbsp; Conclusions: We propose 0.4 &ndash; 3.4 mU/L as a TSH reference range for adults for this platform, which is lower than those presently used in most laboratories. Our findings suggest that intensive screening for thyroid risk factors, especially for TPOAb-positivity, decreases the TSH upper reference limit.&nbsp;</p

Early Onset Hypertension Is Associated With Hypertensive End-Organ Damage Already by MidLife

Early onset hypertension confers increased risk for cardiovascular mortality in the community. Whether early onset hypertension also promotes the development of target end-organ damage (TOD), even by midlife, has remained unknown. We studied 2680 middle-aged CARDIA (coronary artery risk development in young adults) Study participants (mean age 50±4 years, 57% women) who underwent up to 8 serial blood pressure measurements between 1985 and 2011 (age range at baseline 18-30 years) in addition to assessments of echocardiographic left ventricular hypertrophy, coronary calcification, albuminuria, and diastolic dysfunction in 2010 to 2011. Age of hypertension onset was defined as the age at first of 2 consecutively attended examinations with blood pressure ≥140/90 mm Hg or use of antihypertensive medication. Participants were divided in groups by hypertension onset age (<35 years, 35-44 years, ≥45 years, or no hypertension). While adjusting for TOD risk factors, including systolic blood pressure, we used logistic regression to calculate odds ratios for cases (participants with TOD) versus controls (participants without TOD) to examine the relation of hypertension onset age and hypertensive TOD. Compared with normotensive individuals, hypertension onset at age <35 years was related to odds ratios of 2.29 (95% CI, 1.36-3.86), 2.94 (95% CI, 1.57-5.49), 1.12 (95% CI, 0.55-2.29), and 2.06 (95% CI, 1.04-4.05) for left ventricular hypertrophy, coronary calcification, albuminuria, and diastolic dysfunction, respectively. In contrast, hypertension onset at age ≥45 years was not related to increased odds of TOD. Our findings emphasize the importance of assessing age of hypertension onset in hypertensive patients to identify high-risk individuals for preventing hypertensive complications

Haptoglobin Hp1 Variant Does Not Associate with Small Vessel Disease

Haptoglobin (Hp) is a plasma protein that binds free hemoglobin and protects tissues from oxidative damage. An Hp2 allele has been associated with an increased risk of cardiovascular complications. On the other hand, recent studies have suggested that Hp1 allele increases risk to develop severe cerebral small vessel disease. We aimed to replicate this finding in a first-ever stroke patient cohort. Hp was genotyped by PCR and gel electrophoresis in the Helsinki Stroke Aging Memory Study in patients with DNA and magnetic resonance imaging (MRI) available (SAM; n = 316). Lacunar infarcts and white matter lesions (WML) classified by Fazekas grading from brain MRI were associated with Hp genotypes. As population controls, we used participants of Cardiovascular diseases-a sub study of Health 2000 Survey (n = 1417). In the SAM cohort, 63.0% of Hp1-1 carriers (n = 46), 52.5% of Hp1-2 carriers (n = 141) and 51.2% of Hp2-2 carriers (n = 129) had severe WML (p = 0.372). There was no difference in severe WMLs between Hp1-1 vs. Hp1-2 and Hp2-2 carriers (p = 0.201). In addition, 68.9% of Hp1-1 carriers (n = 45), 58.5% of Hp1-2 carriers (n = 135), and 61.8% of Hp2-2 carriers (n = 126) had one or more lacunar lesions (p = 0.472). There was no difference in the number of patients with at least one lacunar infarct between Hp1-1 vs. Hp1-2 and Hp2-2 groups (p = 0.322). Neither was there any difference when diabetic patients (type I and II) were examined separately. Hp1 allele is not associated with an increased risk for cerebral small vessel disease in a well-characterized Finnish stroke patient cohort

Interrelations Between Arterial Stiffness, Target Organ Damage, and Cardiovascular Disease Outcomes

Background-Excess transmission of pressure pulsatility caused by increased arterial stiffness may incur microcirculatory damage in end organs (target organ damage [TOD]) and, in turn, elevate risk for cardiovascular disease (CVD) events.Methods and Results-We related arterial stiffness measures (carotid-femoral pulse wave velocity, mean arterial pressure, central pulse pressure) to the prevalence and incidence of TOD (defined as albuminuria and/or echocardiographic left ventricular hypertrophy) in up to 6203 Framingham Study participants (mean age 50 +/- 15 years, 54% women). We then related presence of TOD to incident CVD in multivariable Cox regression models without and with adjustment for arterial stiffness measures. Cross-sectionally, greater arterial stiffness was associated with a higher prevalence of TOD (adjusted odds ratios ranging from 1.23 to 1.54 per SD increment in arterial stiffness measure, P<0.01). Prospectively, increased carotid-femoral pulse wave velocity was associated with incident albuminuria (odds ratio per SD 1.28, 95% CI, 1.02-1.61; P<0.05), whereas higher mean arterial pressure and central pulse pressure were associated with incident left ventricular hypertrophy (odds ratio per SD 1.37 and 1.45, respectively; P<0.01). On follow-up, 297 of 5803 participants experienced a first CVD event. Presence of TOD was associated with a 33% greater hazard of incident CVD (95% CI, 0-77%; P<0.05), which was attenuated upon adjustment for baseline arterial stiffness measures by 5-21%.Conclusions-Elevated arterial stiffness is associated with presence of TOD and may partially mediate the relations of TOD with incident CVD. Our observations in a large community-based sample suggest that mitigating arterial stiffness may lower the burden of TOD and, in turn, clinical CVD

24-h urinary sodium excretion and the risk of adverse outcomes

AimsThe objective was to evaluate whether sodium intake, assessed with the gold standard 24-h urinary collections, was related to long-term incidence of death, cardiovascular disease (CVD) and diabetes mellitus (DM). MethodsA cohort of 4630 individuals aged 25-64 years collected 24-h urine samples in 1979-2002 and were followed up to 14 years for the incidence of any CVD, coronary heart disease (CHD), stroke, heart failure (HF) and DM event, and death. Cox proportional hazards models were used to estimate the association between the baseline salt intake and incident events and adjusted for baseline age, body mass index, serum cholesterol, prevalent DM, and stratified by sex and cohort baseline year. ResultsDuring the follow-up, we observed 423 deaths, 424 CVD events (288 CHD events, 142 strokes, 139 HF events) and 161 DM events. Compared with the highest quartile of salt intake, persons in the lowest quartile had a lower incidence of CVD (hazard ratio [HR] 0.70; 95% confidence interval [CI], 0.51-0.95, p = .02), CHD (HR 0.63 [95% CI 0.42-0.94], p = .02) and DM (HR 0.52 [95% CI 0.31-0.87], p = .01). The results were non-significant for mortality, HF, and stroke.Conclusion High sodium intake is associated with an increased incidence of CVD and DM.</div

Ambulatory versus home blood pressure monitoring: frequency and determinants of blood pressure difference and diagnostic disagreement

Objectives: Out-of-office blood pressure evaluation assessed using ambulatory (ABP) or home (HBP) monitoring is currently recommended for hypertension management. We evaluated the frequency and determinants of diagnostic disagreement between ABP and HBP measurements. Methods: Cross-sectional data from 1971 participants (mean age 53.8 +/- 11.4 years, 52.6% men, 32% treated) from Greece, Finland and the United Kingdom were analyzed. The diagnostic disagreement between HBP and daytime ABP was regarded as certain when (i) the two methods diagnosed a different blood pressure phenotype, (ii) the absolute HBP-ABP difference was more than 10/5 mmHg (systolic/diastolic) and (iii) ABP and HBP had a more than 5 mmHg difference from the respective hypertension threshold. Results: In 1574 participants (79.9%), there was agreement between HBP and ABP in diagnosing hypertensive phenotypes (kappa 0.70). Of the remaining 397 participants (20.1%) with diagnostic disagreement, 95 had clinically irrelevant HBP-ABP differences, which reduced the disagreement to 15.3%. When cases with ABP and/or HBP differing <= 5 mmHg from the respective hypertension threshold were excluded, the certain disagreement between the two methods was reduced to 8.2%. Significant determinants of the HBP-ABP difference were age, sex, study center, BMI, cardiovascular disease history, office hypertension and antihypertensive treatment. Antihypertensive drug treatment, alcohol consumption and office normotension independently increased the odds of diagnostic disagreement. Conclusion: These data suggest that there is considerable diagnostic agreement between HBP and ABP, and that these methods are interchangeable for clinical decisions in most patients. However, considerable disagreement between the two methods occurs in an appreciable minority, most likely due to methodological and patient-related factors

Genome-wide association study of nocturnal blood pressure dipping in hypertensive patients

Background: Reduced nocturnal fall (non-dipping) of blood pressure (BP) is a predictor of cardiovascular target organ damage. No genome-wide association studies (GWAS) on BP dipping have been previously reported.Methods: To study genetic variation affecting BP dipping, we conducted a GWAS in Genetics of Drug Responsiveness in Essential Hypertension (GENRES) cohort (n = 204) using the mean night-to-day BP ratio from up to four ambulatory BP recordings conducted on placebo. Associations with P< 1 x 10(-5) were further tested in two independent cohorts: Haemodynamics in Primary and Secondary Hypertension (DYNAMIC) (n = 183) and Dietary, Lifestyle and Genetic determinants of Obesity and Metabolic Syndrome (DILGOM) (n = 180). We also tested the genome-wide significant single nucleotide polymorphism (SNP) for association with left ventricular hypertrophy in GENRES.Results: In GENRES GWAS, rs4905794 near BCL11B achieved genome-wide significance (beta = - 4.8%, P = 9.6 x 10(-9) for systolic and beta = - 4.3%, P = 2.2 x 10(-6) for diastolic night-to-day BP ratio). Seven additional SNPs in five loci had P values < 1 x 10(-5). The association of rs4905794 did not significantly replicate, even though in DYNAMIC the effect was in the same direction (beta = - 0.8%, P = 0.4 for systolic and beta = - 1.6%, P = 0.13 for diastolic night-to-day BP ratio). In GENRES, the associations remained significant even during administration of four different antihypertensive drugs. In separate analysis in GENRES, rs4905794 was associated with echocardiographic left ventricular mass (beta = -7.6 g/m(2), P = 0.02).Conclusions: rs4905794 near BCL11B showed evidence for association with nocturnal BP dipping. It also associated with left ventricular mass in GENRES. Combined with earlier data, our results provide support to the idea that BCL11B could play a role in cardiovascular pathophysiology