Left Ventricular Hypertrophy in Hypertension and Nocturnal Blood Pressure

High blood pressure (BP) may not be such an important, sometimes deadly, cardiovascular risk factor if it were not for its adverse effect on target organs, leading to what is frequently called target organ damage. The targets of elevated BP are obviously the vasculature in which the BP is present. The continued stress the blood vessels experience brings about the prototypic vascular smooth muscle response: contraction and subsequent adoptive hypertrophy that would allow long‐term energetic homeostasis. This is shown in hypertrophy on histology, in muscular blood vessels in all organs (easily evident in the retina), and frequently recognized in histology of kidneys and other tissues in hypertensive patients. Parallel hypertrophic changes occur in myocardial muscle cells leading to what is recognized as left ventricular (the ventricle exposed to systemically elevated BP) hypertrophy. These myocardial changes can be recognized clinically by the time‐honored (and frequently overlooked) physical examination (cardiac enlargement by percussion and fourth heart sound by auscultaion), by x‐rays (old way) when the cardiothoracic ratio is elevated, by electrocardiographic changes (another old way), by echocardiography (most frequently utilized diagnostic), and by magnetic resonance imaging (rarely clinically employed because of price and limited availability). Electrocardiographic analysis, which includes additional variables to the classic voltage criteria, can greatly enhance potential diagnosis even in the absence of echocardiography, which is not always readily available even in countries in which resources are not limited, not to mention magnetic resonance imaging.1

Left ventricular hypertrophy in the clinical management of hypertension is not only important because of the typical association but also because the recognition of its long‐recognized adverse prognostic significance2 and its reversible potential.3 Regression of left ventricular hypertrophy is now an accepted way to improve prognosis in hypertension beyond BP control.4

The relationship between left ventricular hypertrophy and hypertension is not straightforward although it was recognized as far back as the 19th century5 and many factors, the inherent variability of BP not the least of them, do not allow deduction of its presence from BP levels.

In the past decades, availability of ambulatory BP monitoring greatly facilitated evaluation of “real” BP in clinical practice.6 In a pioneering study a quarter of a century ago, Verdecchia and colleagues7 found that left ventricular hypertrophy was more closely associated with ambulatory BP than clinic BP but that lack of nocturnal decrease in BP (frequently termed nondipping) was its closest associate. Since then, there have been numerous studies on the issue, many of which supported this finding. Cuspidi and colleagues,8 who extensively contributed to the field and reviewed the evidence, concluded that part of the disagreement between previous studies is because of the questionable repeatability of nondipping. If the nondipping trait is variable then, when combined with inherent BP variability, it may be hard to verify the association. Indeed, they found that when nondipping is persistent (on repeated monitoring) it is better associated with left ventricular hypertrophy.

Why is BP nondipping (or dipping for that matter) so elusive? It is generally believed that BP decreases during sleep because of withdrawal of sympathetic drive9 and perhaps the renin‐angiotensin system.10 Of course, depth of sleep itself, as everybody experiences, is not a terribly reproducible phenomenon, and BP is associated with depth of sleep.9

In addition, sleep and the associated BP reduction is complicated by behavioral patterns. If people wake up at night, most frequently to pass urine, a common occurrence in middle‐aged and older populations (those in whom hypertension and left ventricular hypertrophy are more prevalent), their BP may be taken (during ambulatory monitoring). If such measurements are included in the nighttime average, the values will elevate it spuriously and also reduce the extent of dipping from daytime BP.11, 12 Another behavior that confounds dipping may be daytime napping, because BP decreases during naps similarly to the night sleep average. If a patient naps during daytime monitoring and the daytime sleep BP is included in the daytime average, than again daytime BP will be spuriously lowered and nondipping may occur, despite a preserved decrease in BP during sleep.13, 14 Indeed, when patients nap during the day and get up at night, they will end up categorized as nondippers even though they have the inherent ability to have decreased BP during sleep.15 Alternatively, the dipping rate may be altered by vigorous physical activity during a certain ambulatory monitoring session and not during another, and even if nocturnal BP may be similar, the degree of dipping may vary. Other phenomena, such as orthostatic hypotension,16 a high‐salt diet,17 and obesity18, 19 may also modulate dipping. Moreover, as it is a category (dipper or not), it may introduce problems because of the variability of BP, of sleep, and of associated conditions. When evaluated as a continuous variable, it seems to be at least as reproducible as ambulatory BP.20 Pharmacologic treatment of BP, especially by agents that do not offer even coverage for 24 hours, may also contribute to the mess.

Why is nocturnal BP and nondipping associated with left ventricular hypertrophy? Could it be the longer exposure to elevated BP? Or are both nocturnal BP and nondipping epiphenomena of other factors?

Other than BP, obesity is a strong and BP‐independent predictor of left ventricular hypertrophy, as recently extensively reviewed.21 Of course when hypertension is combined with obesity, as so frequently is the case, the association strengthens. In order to become obese, one usually eats more than necessary (and probably exercises less) in the current nutritional milieu, which also means the consumption of more salt. It so happens that obese and metabolic syndrome patients' BP is frequently salt sensitive, particularly among Chinese patients,22 in whom napping is also common,23 and nondippers.24 These traits are also common in hypertensives; therefore, it is difficult to discern between the effects of all these factors on left ventricular hypertrophy. In all likelihood, they affect each other, and, with obstructive sleep apnea a salt‐sensitive state in itself,25 is also likely contributes to the association of nondipping and left ventricular hypertrophy. The question of whether control of nocturnal BP will allow better left ventricular mass regression remains to be demonstrated. Even less certain is improvement of nocturnal BP dipping. Although it was shown that a low‐salt diet and diuretics can improve dipping, this was investigated in only small studies. Translating these findings to clinical practice remains elusive although promising, but many dislike extensive diuretic use. In addition, although bedtime dosing is also promising,26, 27 it is not always successful, and in my personal experience somewhat disappointing in this respect. Thus, for now, prevention seems best. Early successful treatment (if not prevention) of hypertension includes maintaining healthy body mass and refraining from excess salt intake. These are difficult to achieve and thus both left ventricular hypertrophy and nondipping are here to stay. It is for us, the clinicians, to work harder to prevent them.