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Genetic and environmental factors in development of hypertension

Zanchetti, Alberto

doi: 10.1097/HJH.0000000000001102

Istituto Auxologico Italiano IRCCS and Centro Interuniversitario Fisiologia Clinica e Ipertensione, Università degli Studi di Milano, Milan, Italy

Correspondence to Professor Alberto Zanchetti, Istituto Auxologico Italiano IRCCS and Centro Interuniversitario di Fisiologia Clinica e Ipertensione, Università degli Studi di Milano, Via F. Sforza, 32, 20122, Milan, Italy. E-mail: or

It is commonly agreed that both genetic and environmental factors play a significant role in the development of hypertension and associated cardiovascular and metabolic disease. It has long been known that environment can be involved very early as maternal environmental factors during pregnancy (e.g. maternal undernutrition and overnutrition, lack of micronutrients or exposure to toxins, and stress during pregnancy) are important determinants of future disease. In the current issue of the Journal of Hypertension, Berthold Hocher's group (J. Li et al., pp. 2111–2126) reviews recent epidemiological and experimental evidence showing that paternal environmental factors, before conception and during sperm development, also determine the health of the offspring in later life. In an accompanying editorial commentary, Hamet (pp. 2136–2137) urges further efforts to integrate environmental, epigenetic, and genetic efforts for a holistic understanding of the problem. He suggests one of the future tasks could be to identify the genomic determinants of interactions with environment, particularly when influencing the development of offspring, and determine their future susceptibility to disease.

Increasing evidence has been produced recently favoring a role of elevated plasma uric acid in increasing the risk of incident hypertension. Scheepers et al. (pp. 2147–2154), on the basis of a population study, now show that gene variants of the enzyme xanthine oxidoreductase (XOR), the only enzyme capable of producing uric acid, are associated with pulse pressure and incident hypertension. It is the process of uric acid production by XOR, and not hyperuricemia per se, that may be associated with hypertension as a result of oxidative stress and endothelial dysfunction. In an accompanying editorial commentary, Schmitz and Brand (pp. 2138–2139) discuss the possibility that intraendothelial xantine oxidase activity and increased reactive oxygen species production might be a factor involved in endothelial dysfunction leading to the development of essential hypertension.

Borghi et al. (pp. 2155–2163), analyzing data from the European Study on Cardiovascular Risk Prevention and Management in Usual Daily Practice, involving 7641 individuals with at least one major cardiovascular risk factor, but free from cardiovascular disease, find small, but statistically significant, associations between lipid levels and blood pressure (BP). Chuang et al. (pp. 2164–2171) report that, in a prospective cohort study from Taiwan, vegetarians had a 34% lower risk for hypertension after adjusting for age and sex. Studying a Chinese cohort of 44 494 singleton live births delivered at gestational ages of 20–42 weeks, N. Li et al. (pp. 2243–2247) did not find any significant difference in the risk of preterm birth in women hypertensive prior to pregnancy in comparison with those known to be normotensive.

Another group of articles in the current issue of the journal focus on diagnostic aspects. Interest for unconventional methods of BP measurement in diagnosis of hypertension is witnessed by three articles. Wohlfahrt et al. (pp. 2180–2186), in a large randomized sample of the Brno population, have compared manual office BP, the usual method for diagnosing hypertension, with automated office BP taking multiple readings with patients resting quietly alone: they report that values of 131/85.5 mmHg correspond to manual BP of 140/90 mmHg. The investigators of the international ARTEMIS consortium have compared clinic and ambulatory BP values in 14 143 individuals from 27 countries across five continents and found an unbalanced distribution of white-coat and masked hypertension prevalence across different countries. Salazar et al. (pp. 2248–2252) report that nocturnal SBP and DBP had the highest ability to predict onset of preeclampsia/eclampsia in normotensive pregnant women with high-risk pregnancy. Commenting these data, Bilo and Parati (pp. 2140–2142) remark the findings may boost a routine use of ambulatory BP monitoring in the critical phase of pregnancy (around the 30th week), although they caution that the evidence provided by Salazar et al. is restricted to high-risk pregnancies, and further evidence is needed to extend the practice to normal pregnancies.

Two articles focus on diagnostic procedures for identification of primary aldosteronism, one of the most frequent forms of secondary hypertension. Mulatero et al. (pp. 2253–2257) have investigated the level of knowledge and application of the Endocrine Society guidelines for diagnosis and management of primary aldosteronism among general practitioners in Italy and Germany and found these guidelines are not all known and applied, probably resulting in marked underdiagnosis of this condition. In an accompanying editorial commentary, Gordon (pp. 2143–2144) suggests a solution giving more prominence to hypertension in undergraduate and postgraduate medical curricula, and possibly recognizing hypertension as a specialty within internal medicine.

Another large group of articles are devoted to diagnosis of hypertension-associated organ damage and investigation of their mechanisms. Carrara et al. (pp. 2199–2205) find that restoration of normal vitamin D levels after 8-week cholecalciferol treatment is able to improve endothelial function (as measured by flow-mediated dilatation) in hypertensive patients with hypovitaminosis D. Kim et al. (pp. 2206–2219) have investigated the role of histone deacetylase (HDAC) in angiotensin II induced hypertension in mice by showing a selective inhibitor of class II HDAC reduced elevated SBP and inhibited vascular smooth muscle cell hypertrophy and hyperplasia. In a multiethnic cohort of young British adults, Faconti et al. (pp. 2220–2226) find that augmentation index, but not pulse wave velocity, is higher in south Asians compared with whites and suggest that early adult augmentation index could be a useful tool for testing components of excess cardiovascular risk in some ethnic minority groups. Mivelaz et al. (pp. 2227–2232) report that measurement of carotid intima–media thickness in nonsedated infants less than 1 year of age is feasible with good interobserver variability. Lehmann et al. (pp. 2233–2242) have studied the influence of prehypertension and hypertension on coronary artery calcification progression: in the 3841 patients, aged 45–74 years, of the Heinz Nixdorf Recall study. The authors report that elevated risk of rapid progression of calcification already occurs in prehypertension, and more so in hypertension.

Tellez-Plaza et al. (pp. 2266–2273) have assessed the attributable risk of renal dysfunction on mortality and hospitalization for coronary heart disease or stroke in the 52 000 patients with at least one main cardiovascular risk factor of the ESCARVAL-RISK study and found that decreased estimated glomerular filtration rates were associated with additional attributed risk of mortality and cardiovascular disease. Zamami et al. (pp. 2274–2279) have done renal biopsies in patients with nonnephrotic chronic kidney disease and report that combination of high BP and hyalinosis was associated with increased proteinuria. Antikainen et al. (pp. 2280–2286) have assessed the prognostic significance of ECG left ventricular hypertrophy (LVH) in the very old (80 years and over) of the HYpertension in the Very Elderly Trial (HYVET) and found the use of Cornell voltage and Cornell product criteria for LVH predicted the risk of cardiovascular disease and stroke, whereas only Cornell product was associated with an increased risk of heart failure. In their editorial commentary, Wachtell and Okin et al. (pp. 2145-2146) underline that Antikainen et al.'s study has several novel observations: the first is that Sokolow–Lyon voltage criteria do not perform well in the elderly, possibly because of changes in heart position that do not affect Cornell voltage-duration product, another is that incident stroke is more common than myocardial infarction in the elderly.

A final group of articles in the current issue of the journal focus on therapeutic aspects of hypertension. Sahebkar et al. (pp. 2127–2135) have done a systematic review and meta-analysis of randomized controlled trials on the effects of Nagella sativa (black seed) on BP, finding a small, but significant, reduction of both SBP and DBP values. Napoli et al. (pp. 2287–2297), in a large randomized double-blind study comparing a fixed dose combination of the sulphydril–containing angiotensin-converting enzyme inhibitor, zofenopril, and hydrochlorothiazide versus the angiotensin receptor blocker, irbesartan, and hydrochlorothiazide, find comparable antihypertensive and metabolic responses to the two fixed-dose combinations. Finally, Musicha et al. (pp. 2172–2179) complain that in Malawi, though screening for hypertension and diabetes identifies a large number of individuals in need of further clinical assessment, access to clinical services and retention in care require improved strategies.

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Conflicts of interest

There are no conflicts of interest.

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